Rapid identification of nonblood sterile site broth cultures using the FilmArray blood culture identification panel

The FilmArray Blood Culture Identification Panel was validated for nonblood sterile site specimens with clinical impact of rapid identification compared to conventional diagnostics. The panel accurately identified target organisms from 98% of positive broth cultures a median 1.1?day faster than conventional techniques (P?<?0.0001) with potential clinical impact in 22% of cases.     

The Tricky Tear Trough: A Review of Topical Cosmeceuticals for Periorbital Skin Rejuvenation

There is a growing demand for noninvasive anti-aging products for which the periorbital region serves as a critical aspect of facial rejuvenation. This article reviews a multitude of cosmeceutical ingredients that have good scientific data, specifically for the periorbital region. Topical treatment options have exponentially grown from extensively studied retinoids, to recently developed technology, such as growth factors and peptides. With a focus on the periorbital anatomy, the authors review the mechanisms of action of topical cosmeceutical ingredients, effectiveness of ingredient penetration through the stratum corneum, and validity of clinical trials.Due to the Baby Boomer’s continual pursuit to maintain a youthful appearance, there is a new paradigm in treating the signs of aging. The periorbital region serves as a window to a person’s chronological age. Aging photodamaged skin demonstrates epidermal atrophy, pigmentary changes, and the formation of dynamic and resting rhytides. Patients are commonly concerned about the appearance of dark circles, crow’s feet, eyelid bags, dry skin, thin skin, and just “looking tired.” They often seek advice about which treatments are most effective for periorbital rejuvenation. Although aging is inevitable, there are certain features of the periorbital skin that can be addressed to minimize the aged appearance.There are many effective treatment options including surgical measures and nonsurgical modalities, such as fillers, neuromodulators, lasers, and light technology, but these are costly and have the potential for greater side effects. Therefore, a minimally invasive treatment, such as a topical cosmeceutical, is often the desired first line of defense.A search for “crow’s feet” on Amazon.com revealed 2,471 products. The upper limit of the price range was more than $1,000 for a 15mL eye serum claiming to “eliminate wrinkles, reduce dark circles, and hydrate the skin around the eyes.” This helps elucidate the demand for products to address these common concerns in the periorbital region.What follows is a review of the common ingredients in topical cosmeceuticals utilized for periorbital rejuvenation.     

GeneYenta: A Phenotype­Based Rare Disease Case Matching Tool Based on Online Dating Algorithms for the Acceleration of Exome Interpretation

Advances in next‐generation sequencing (NGS) technologies have helped reveal causal variants for genetic diseases. In order to establish causality, it is often necessary to compare genomes of unrelated individuals with similar disease phenotypes to identify common disrupted genes. When working with cases of rare genetic disorders, finding similar individuals can be extremely difficult. We introduce a web tool, GeneYenta, which facilitates the matchmaking process, allowing clinicians to coordinate detailed comparisons for phenotypically similar cases. Importantly, the system is focused on phenotype annotation, with explicit limitations on highly confidential data that create barriers to participation. The procedure for matching of patient phenotypes, inspired by online dating services, uses an ontology­based semantic case matching algorithm with attribute weighting. We evaluate the capacity of the system using a curated reference data set and 19 clinician entered cases comparing four matching algorithms. We find that the inclusion of clinician weights can augment phenotype matching.     

Striatal Morphology is Associated with Tobacco Cigarette Craving

The striatum has a clear role in addictive disorders and is involved in drug-related craving. Recently, enhanced striatal volume was associated with greater lifetime nicotine exposure, suggesting a bridge between striatal function and structural phenotypes. To assess this link between striatal structure and function, we evaluated the relationship between striatal morphology and this brain region''s well-established role in craving. In tobacco smokers, we assessed striatal volume, surface area, and shape using a new segmentation methodology coupled with local shape indices. Striatal morphology was then related with two measures of craving: state-based craving, assessed by the brief questionnaire of smoking urges (QSU), and craving induced by smoking-related images. A positive association was found between left striatal volume and surface area with both measures of craving. A more specific relationship was found between both craving measures and the dorsal, but not in ventral striatum. Evaluating dorsal striatal subregions showed a single relationship between the caudate and QSU. Although cue-induced craving and the QSU were both associated with enlarged striatal volume and surface area, these measures were differentially associated with global or more local striatal volumes. We also report a connection between greater right striatal shape deformations and cue-induced craving. Shape deformations associated with cue-induced craving were specific to striatal subregions involved in habitual responding to rewarding stimuli, which is relevant given the habitual nature of cue-induced craving. The current findings confirm a relationship between striatal function and morphology and suggest that variation in striatal morphology may be a biomarker for craving severity.     

Phosphorylation of Ribosomal Protein S6 Mediates Mammalian Target of Rapamycin Complex 1–Induced Parathyroid Cell Proliferation in Secondary Hyperparathyroidism

Secondary hyperparathyroidism is characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation. However, the molecular pathways mediating the increased parathyroid cell proliferation remain undefined. Here, we found that the mTOR pathway was activated in the parathyroid of rats with secondary hyperparathyroidism induced by either chronic hypocalcemia or uremia, which was measured by increased phosphorylation of ribosomal protein S6 (rpS6), a downstream target of the mTOR pathway. This activation correlated with increased parathyroid cell proliferation. Inhibition of mTOR complex 1 by rapamycin decreased or prevented parathyroid cell proliferation in secondary hyperparathyroidism rats and in vitro in uremic rat parathyroid glands in organ culture. Knockin rpS6^p−/− mice, in which rpS6 cannot be phosphorylated because of substitution of all five phosphorylatable serines with alanines, had impaired PTH secretion after experimental uremia- or folic acid–induced AKI. Uremic rpS6^p−/− mice had no increase in parathyroid cell proliferation compared with a marked increase in uremic wild–type mice. These results underscore the importance of mTOR activation and rpS6 phosphorylation for the pathogenesis of secondary hyperparathyroidism and indicate that mTORC1 is a significant regulator of parathyroid cell proliferation through rpS6.