Tripartite Motif-Containing Protein 32 (TRIM32): What Does It Do for Skeletal Muscle?

Tripartite motif-containing protein 32 (TRIM32) is a member of the tripartite motif family and is highly conserved from flies to humans. Via its E3 ubiquitin ligase activity, TRIM32 mediates and regulates many physiological and pathophysiological processes, such as growth, differentiation, muscle regeneration, immunity, and carcinogenesis. TRIM32 plays multifunctional roles in the maintenance of skeletal muscle. Genetic variations in the TRIM32 gene are associated with skeletal muscular dystrophies in humans, including limb-girdle muscular dystrophy type 2H (LGMD2H). LGMD2H-causing genetic variations of TRIM32 occur most frequently in the C-terminal NHL (ncl-1, HT2A, and lin-41) repeats of TRIM32. LGMD2H is characterized by skeletal muscle dystrophy, myopathy, and atrophy. Surprisingly, most patients with LGMD2H show minimal or no dysfunction in other tissues or organs, despite the broad expression of TRIM32 in various tissues. This suggests more prominent roles for TRIM32 in skeletal muscle than in other tissues or organs. This review is focused on understanding the physiological roles of TRIM32 in skeletal muscle, the pathophysiological mechanisms mediated by TRIM32 genetic variants in LGMD2H patients, and the correlations between TRIM32 and Duchenne muscular dystrophy (DMD).

Tripartite motif-containing protein 32 regulates Ca2+ movement in skeletal muscle.

Mutations in tripartite motif-containing protein 32 (TRIM32), especially in NHL repeats, have been found in skeletal muscle in patients with type 2H limb-girdle muscular dystrophy (LGMD2H). However, the roles of the NHL repeats of TRIM32 in skeletal muscle functions have not been well addressed. In the present study, to examine the functional role(s) of the TRIM32 NHL repeats in skeletal muscle, TRIM32-binding proteins in skeletal muscle were first searched using a binding assay and MALDI-TOF/TOF. Sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 1a (SERCA1a) was found to be a TRIM32-binding protein. Next, a deletion mutant of TRIM32 missing the NHL repeats (NHL-Del) was expressed in mouse primary skeletal myotubes during myoblast differentiation into myotubes. Ca2+ movement in the myotubes was examined using single-cell Ca2+ imaging. Unlike wild-type (WT) TRIM32, NHL-Del did not enhance the amount of Ca2+ release from the sarcoplasmic reticulum (SR), Ca2+ release for excitation-contraction (EC) coupling, or extracellular Ca2+ entry via store-operated Ca2+ entry (SOCE). In addition, even compared with the vector control, NHL-Del resulted in reduced SOCE due to reduced expression of extracellular Ca2+ entry channels. Transmission electron microscopy (TEM) observation of the myotubes revealed that NHL-Del induced the formation of abnormal vacuoles and tubular structures in the cytosol. Therefore, by binding to SERCA1a via its NHL repeats, TRIM32 may participate in the regulation of Ca2+ movement for skeletal muscle contraction and the formation of cellular vacuoles and tubular structures in skeletal muscle. Functional defects in TRIM32 due to mutations in NHL repeats may be pathogenic toward LGMD2H.

Clinical outcomes of adults with eosinophilic esophagitis with severe stricture.

BACKGROUND AND AIMS: Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus. Its prevalence has been increasing steadily over the past 3 decades. The prognosis of patients with EoE presenting with severe esophageal strictures is poorly understood. The aim of this study was to describe the clinical outcomes of patients with EoE with severe strictures and identify factors associated with a greater likelihood of improvement in esophageal diameter. METHODS: This study is a retrospective chart review of patients with EoE with severe stricture, defined as an esophageal diameter of 10 mm or less at one point in their disease course. Each patient's clinical course was followed during standard-of-care follow-up with medical or dietary therapy in conjunction with repeated esophageal dilation. Multivariate regression analysis was performed to determine which variables are associated with endoscopic response, defined by an improvement in esophageal diameter to 13 mm and to 15 mm. RESULTS: From a cohort of 1091 adults with EoE, severe strictures were identified in 66 patients (7%). Of the 66 patients, 59 (89%) achieved an esophageal diameter of ≥13 mm and 43 (65%) achieved ≥15 mm. Initial diameter (odds ratio, 1.58; 95% confidence interval, 1.06-2.35; P = .025) and histologic remission (odds ratio, 34.97; 95% confidence interval, 6.45-189.49; P < .0001) were significantly associated with achieving a diameter ≥15 mm. Age at diagnosis, gender, and number of months to maximum esophageal diameter were not associated with achieving either diameter. CONCLUSIONS: Most patients with EoE with severe stricture experienced improvement in esophageal diameter to ≥15 mm with treatment, suggesting that the currently available treatment options are effective for patients with severe strictures. The most significant factors associated with disease reversibility are initial esophageal diameter and histologic remission.

How I Approach Dysphagia.

PURPOSE OF REVIEW: This review presents an overview of the diagnostic approach to esophageal dysphagia and summarizes recent epidemiological trends and technical advancements. RECENT FINDINGS: The evaluation of dysphagia begins with a detailed history followed by endoscopy to evaluate for any structural abnormalities including malignancy. This is especially true given the emergence of eosinophilic esophagitis (EoE) as a dominant cause of esophageal dysphagia. In fact, it is now standard practice to obtain esophageal biopsies during endoscopy performed to evaluate dysphagia, since EoE can present without the characteristic mucosal features of rings, furrows, and exudate. Achalasia is also more frequently encountered since the introduction of high-resolution manometry (HRM) and the Chicago Classification into clinical practice. The Chicago Classification provides a stepwise diagnostic algorithm for evaluating HRM studies and systematically diagnosing esophageal motility disorders. Lastly, the functional lumen imaging probe (FLIP) is a novel technology that has added insight into both achalasia and EoE. Measuring esophageal distensibility with FLIP has useful prognostic implications for both diseases, and FLIP can identify motility abnormalities in achalasics not detected with HRM. A careful history is key to the efficient evaluation of dysphagia, and endoscopy is usually the first diagnostic study to obtain. For patients with prominent reflux symptoms, an empiric trial with proton pump inhibitors is reasonable then because reflux disease is such a common cause of dysphagia. Thereafter, patients should undergo HRM to evaluate for a motility disorder, and FLIP can provide complementary data to guide management.

Treatment Gap in Primary Prevention Patients Presenting With Acute Coronary Syndrome.

Previous studies assessing healthcare provider compliance to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines indicate a significant underuse of statin therapy at appropriate intensity. However, data are limited in primary prevention patients. Our study aimed to evaluate the impact of the 2013 ACC/AHA guidelines through a retrospective analysis of primary prevention patients presenting with first time acute coronary syndrome (ACS). We retrospectively calculated the 10-year predicted Atherosclerotic Cardiovascular Disease (10yASCVD) risk in 1,265 patients ages 40 to 75 who presented with ACS and no previous ASCVD. In patients without known ambulatory systolic blood pressure, a multivariable linear regression model was used to predict outpatient systolic blood pressure. Outcomes analyzed in each 10yASCVD category included statin status and statin intensity (high/medium/low) with further categorization by type of ACS event and date of left heart catheterization. In both primary analysis and sensitivity analysis (patients with predicted systolic blood pressure), statistical significance was shown with respect to overall statin status, ST Elevation Myocardial Infarction, and date of left heart catheterization. In summary, retrospective calculation of 10yASCVD in patients with a first ACS event showed a significant number of ACS patients would have qualified for statin therapy per 2013 ACC/AHA guidelines before their event but had not been initiated on one.

Consumer Perception of the Food and Drug Administration's Newest Recommended Food Facility Inspection Format: Words Matter.

The Food and Drug Administration recommended restaurant inspection scores change to a format that incorporated three new categories of violations: priority, priority foundation, and core. It was uncertain whether interested consumers would value the more in-depth information or become more confused. The purpose of this study was to assess consumer perception of the recommended inspection system. Data were collected from an online survey. Results showed that consumers want convenient access to the information either online or on the wall of restaurants, and some consumers do want to read inspection reports and use them in making dining decisions. Choice of restaurant inspection format did appear to change consumer understanding and perceptions about some of the violations. Results also demonstrated the importance of the words used to categorize violations.

Inspector Perceptions of the Food and Drug Administration's Newest Recommended Food Facility Inspection Format: Training Matters.

The Food and Drug Administration publishes the Food Code to guide restaurant inspections. The most recent version proposes a three-tier system categorizing violations as priority, priority foundation, and core. This study used a scenario-based questionnaire to examine inspector perceptions and preferences for inspection formats. Results suggest that inspectors would be able to maintain consistent evaluations when changing to the three-tier system, although the classifying terms under the three-tier system were confusing. Additionally, inspectors were not very positive about the new system; they were concerned that the new system would not be easy to understand and use, inspections would take a longer time, it would not accurately reflect the amount of risk associated with violations, and it would not be easy for consumers and managers to understand and use. The results suggest the need for additional training for inspectors before adoption, especially on the rationale and benefits of changing to a three-tier system.

Arthroscopic detection of medial meniscal injury with the use of a joint distractor in small-breed dogs.

The goal of the present study was to evaluate the diagnostic value of a joint distractor in arthroscopy in small-breed dogs. Sixty stifle joints, which were collected from thirty cadavers, were used in this study. To simulate different injuries, no medial meniscal tear, a full-thickness vertical longitudinal tear, a partial-thickness vertical longitudinal tear, full- and partial-thickness vertical longitudinal tears, or a peripheral detachment were created on the caudal horn of the medial meniscus of each stifle joint along with rupture of the cranial cruciate ligament. Each stifle joint then underwent arthroscopy with and without a joint distractor. The sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and correct classification rate (CCR) for the diagnosis of each type of medial meniscus pathology were calculated. For arthroscopy with and without a joint distractor, the Sn was 85% and 60%, the Sp was 96% and 92%, the PPV was 85% and 65%, the NPV was 96% and 90%, and the CCR was 94% and 86%, respectively. Arthroscopy is an effective diagnostic method for the assessment of medial meniscal pathologies in small-breed dogs, especially when performed with the aid of a joint distractor.

Persistence of atopic dermatitis (AD): A systematic review and meta-analysis.

BACKGROUND: Previous studies found conflicting results about whether childhood atopic dermatitis (AD) persists into adulthood. OBJECTIVE: We sought to determine persistence rates and clinical factors associated with prolonged AD. METHODS: A systematic review was performed in MEDLINE, EMBASE, Scopus, GREAT, LILACS, Web of Science, Academic Search Complete, and Cochrane Library. Meta-analysis was performed using Kaplan-Meier plots and random-effects proportional hazards regression. RESULTS: In total, 45 studies including 110,651 subjects spanning 434,992 patient-years from 15 countries were included. In pooled analysis, 80% of childhood AD did not persist by 8 years and less than 5% persisted by 20 years after diagnosis (mean ± SE: 6.1 ± 0.02 years). Children with AD that persisted already for more than 10 years (8.3 ± 0.08 years) had longer persistence than those with 3 (3.2 ± 0.02 years) or 5 (6.8 ± 0.06 years) years of persistence. Children who developed AD by age 2 years had less persistent disease (P < .0001). Persistence was greater in studies using patient-/caregiver-assessed versus physician-assessed outcomes, female versus male patients (P ≤ .0006), but not in those with sensitivity to allergens (P = .90). Three studies found prolonged persistence with more severe AD. LIMITATIONS: Some studies did not capture recurrences later in life. CONCLUSIONS: Most childhood AD remitted by adulthood. However, children with already persistent disease, later onset, and/or more severe disease have increased persistence.

Yelp Versus Inspection Reports: Is Quality Correlated With Sanitation in Retail Food Facilities?

Consumer-generated restaurant review sites offer a wealth of information about dining options. These sites are based on consumers' experiences; therefore, it is useful to assess the relevance between restaurant review (for food quality) and retail food facilities (RFFs) inspection results (for sanitation) from health departments. This study analyzed New York City restaurant ratings on Yelp.com to determine if there was a relationship to RFFs' violation scores for those same facilities found on the New York City Department of Health and Mental Hygiene web pages. In addition, we assessed differences between RFFs defined on Yelp as quick service versus full service, and chains versus nonchains. Yelp ratings were found to be correlated only with sanitation in chain RFFs.

Thermoresponsive Polymer and Fluorescent Dye Hybrids for Tunable Multicolor Emission.

Fully reversible emission color change is achieved by blending a thermoresponsive polymer with dye hybrids. The emission color can be tuned by changing the mixing ratio of each polymer-dye hybrid.

Thermo-responsive poly(2-isopropyl-2-oxazoline) and tetraphenylethene hybrids for stimuli-responsive photoluminescence control.

Poly(2-isopropyl-2-oxazoline) (POx), a typical thermo-responsive polymer, was conjugated with a tetraphenylethene derivative, having aggregation induced emission behavior, towards the thermal control of their fluorescence emission. The poly(2-isopropyl-2-oxazoline)-tetraphenylethene hybrids selectively formed a host-guest complex with γ-cyclodextrin. The poly(2-isopropyl-2-oxazoline)-tetraphenylethene hybrids and its host-guest complex with γ-cyclodextrin showed opposite on-off switching of fluorescence emission upon temperature change.

Dendrimer porphyrin-coated gold nanoshells for the synergistic combination of photodynamic and photothermal therapy.

A dendrimer porphyrin (DP)-coated gold nanoshell (AuNS-DP) was prepared for the synergistic combination of photodyanmic and photothermal therapy. The resultant AuNS-DP successfully exhibited the generation of reactive oxygen species (ROS) as well as photothermal effect for the simultaneous application of photodynamic therapy (PDT) and photothermal therapy (PTT).

Supramolecular coordination polymer formed from artificial light-harvesting dendrimer.

We report the formation of supramolecular coordination polymers formed from multiporphyrin dendrimers (PZnPM; M = FB or Cu), composed of the focal freebase porphyrin (PFB) or cupper porphyrin (PCu) with eight zinc porphyrin (PZn) wings, and multipyridyl porphyrins (PyPM; M = FB or Cu), PFB or PCu with eight pyridyl groups, through multiple axial coordination interactions of pyridyl groups to PZns. UV-vis absorption spectra were recorded upon titration of PyPFB to PZnPFB. Differential spectra, obtained by subtracting the absorption of PZnPFB without guest addition as well as the absorption of PyPFB, exhibited clear isosbestic points with saturation binding at 1 equiv addition of PyPFB to PZnPFB. Job's plot analysis also indicated 1:1 stoichiometry for the saturation binding. The apparent association constant between PZnPFB and PyPFB (2.91 × 10(6) M(-1)), estimated by isothermal titration calorimetry, was high enough for fibrous assemblies to form at micromolar concentrations. The formation of a fibrous assembly from PZnPFB and PyPFB was visualized by atomic force microscopy and transmission electron microscopy (TEM). When a 1:1 mixture solution of PZnPFB and PyPFB (20 µM) in toluene was cast onto mica, fibrous assemblies with regular height (ca. 2 nm) were observed. TEM images obtained from 1:1 mixture solution of PZnPFB and PyPFB (0.1 wt %) in toluene clearly showed the formation of nanofibers with a regular diameter of ca. 6 nm. Fluorescence emission measurement of PZnPM indicated efficient intramolecular energy transfer from PZn to the focal PFB or PCu. By the formation of supramolecular coordination polymers, the intramolecular energy transfer changed to intermolecular energy transfer from PZnPM to PyPM. When the nonfluorescent PyPCu was titrated to fluorescent PZnPFB, fluorescence emission from the focal PFB was gradually decreased. By the titration of fluorescent PyPFB to nonfluorescent PZnPCu, fluorescence emission from PFB in PyPFB was gradually increased due to the efficient energy transfer from PZn wings in PZnPCu to PyPFB.

Study on the Catalytic Activity of Noble Metal Nanoparticles on Reduced Graphene Oxide for Oxygen Evolution Reactions in Lithium-Air Batteries.

Among many challenges present in Li-air batteries, one of the main reasons of low efficiency is the high charge overpotential due to the slow oxygen evolution reaction (OER). Here, we present systematic evaluation of Pt, Pd, and Ru nanoparticles supported on rGO as OER electrocatalysts in Li-air cell cathodes with LiCF3SO3-tetra(ethylene glycol) dimethyl ether (TEGDME) salt-electrolyte system. All of the noble metals explored could lower the charge overpotentials, and among them, Ru-rGO hybrids exhibited the most stable cycling performance and the lowest charge overpotentials. Role of Ru nanoparticles in boosting oxidation kinetics of the discharge products were investigated. Apparent behavior of Ru nanoparticles was different from the conventional electrocatalysts that lower activation barrier through electron transfer, because the major contribution of Ru nanoparticles in lowering charge overpotential is to control the nature of the discharge products. Ru nanoparticles facilitated thin film-like or nanoparticulate Li2O2 formation during oxygen reduction reaction (ORR), which decomposes at lower potentials during charge, although the conventional role as electrocatalysts during OER cannot be ruled out. Pt-and Pd-rGO hybrids showed fluctuating potential profiles during the cycling. Although Pt- and Pd-rGO decomposed the electrolyte after electrochemical cycling, no electrolyte instability was observed with Ru-rGO hybrids. This study provides the possibility of screening selective electrocatalysts for Li-air cells while maintaining electrolyte stability.

Cascade sensing of gold and thiols with imidazole-bearing functional porphyrins.

An imidazole-bearing zinc porphyrin (PZn) has been designed for the selective detection of Au(3+), and the porphyrin and gold complex (PZn·Au(3+)) can additionally be used to identify gold-binding functional groups such as cysteine residues and other mercaptans.

The effects of dendrimer size and central metal ions on photosensitizing properties of dendrimer porphyrins.

A series of dendrimer porphyrins (G(n)DP(M); n = generation of dendrimer, n = 1-3; M = coordination metal, M = freebase, Zn, Pt) were prepared and their photosensitizing properties were compared. All G(n)DP(M) exhibited sharp absorption in organic solvents. However, the Soret absorptions of G(n)DP(M)(CO(2)H) in 10 mM phosphate buffer solution (pH = 7.4) are broader than those of G(n)DP(M) in organic solvents, indicating inhomogeneous microenvironments of the focal porphyrin derivatives. All G(3)DP(M)(CO(2)H) successfully formed globular polyion complex micelles that were uniform in size. Under dark conditions, all G(n)DP(M)(CO(2)H) showed negligible cytotoxicity. However, all samples exhibited concentration-dependent photocytotoxicity under light irradiation. In vitro photocytotoxicity as well as singlet oxygen generation revealed that G(3)DP(Zn)(CO(2)H) is the best dendritic PS of the three different dendrimer porphyrin species.

Fabrication of multifunctional layer-by-layer nanocapsules toward the design of theragnostic nanoplatform.

Self-assembled polymeric nanocapsules (NCs) that incorporate dendrimer porphyrin (DP) in the shells and superparamagnetic iron oxide nanoparticles (SPIONs) in the cores are fabricated to create a theragnostic platform for the application in photodynamic therapy (PDT) and magnetic resonance imaging (MRI). SPIONs-embedded polystyrene NPs (SPIONs@PS) are used as a template to build up multilayered NCs. The formation of PAH/DP multilayer on the SPIONs@PS is monitored by zeta-pential and fluorescence emission measurement, because the porphyrin unit in the core of DP has strong red fluorescence emission. NCs have strong enough magnetic property (>20 emu/g) for MRI application with typical superparamagnetic behavior, where the linear correlation of R2 and Fe concentration at diluted conditions led to corresponding T2 relaxivity coefficient (r2) value of 93.5 mM(-1) s(-1). Cell viability study upon light irradiation reveals that NCs can successfully work in photosensitizer formulation for PDT.

Detuned surface plasmon resonance scattering of gold nanorods for continuous wave multilayered optical recording and readout.

In a multilayered structure of absorptive optical recording media, continuous-wave laser operation is highly disadvantageous due to heavy beam extinction. For a gold nanorod based recording medium, the narrow surface plasmon resonance (SPR) profile of gold nanorods enables the variation of extinction through mulilayers by a simple detuning of the readout wavelength from the SPR peak. The level of signal extinction through the layers can then be greatly reduced, resulting more efficient readout at deeper layers. The scattering signal strength may be decreased at the detuned wavelength, but balancing these two factors results an optimal scattering peak wavelength that is specific to each layer. In this paper, we propose to use detuned SPR scattering from gold nanorods as a new mechanism for continuous-wave readout scheme on gold nanorod based multilayered optical storage. Using this detuned scattering method, readout using continuous-wave laser is demonstrated on a 16 layer optical recording medium doped with heavily distributed, randomly oriented gold nanorods. Compared to SPR on-resonant readout, this method reduced the required readout power more than one order of magnitude, with only 60 nm detuning from SPR peak. The proposed method will be highly beneficial to multilayered optical storage applications as well as applications using a continuous medium doped heavily with plasmonic nanoparticles.

Dual stimuli-responsive dendritic-linear block copolymers.

Dendritic-linear block copolymers that have pH responsive poly(benzyl ether) dendrons and temperature responsive PiPrOx chains have been designed by copper-mediated click reactions. These copolymers exhibit sharp thermal transitions with a wide range of pH-dependent thermal transition temperatures.