Minimally Complex Renal Cysts: Outcomes and Ultrasound Evaluation Compared with Contrast-Enhanced Cross-Sectional Imaging Bosniak Classification

We correlated contrast-enhanced cross-sectional imaging and outcomes to assess the reproducibility of ultrasonographic criteria for renal minimally complex (MC) cysts. From 2003 to 2015, 143 cysts were described as complex or MC by ultrasound (US). After exclusions, 98 US studies were retrospectively evaluated and compared with computed tomography (CT)/magnetic resonance imaging (MRI). At sonography, 51 were MC cysts and 47 were complexes according to two independent observers. Inter-observer agreement for US was 0.704 and 0.745 for CT/MRI. Of 51 cysts classified as MC by US, 38 were Bosniak I/II and 6 were Bosniak IIF by CT/MRI. In 7, there were no cross-sectional images; however, they were stable for at least 2 y. Of 47 complex cysts, 9 were Bosniak II, 22 Bosniak IIF, 8 Bosniak III and 8 Bosniak IV. No Bosniak III/IV cysts by CT/MRI were classified as MC by US. Our results indicate that US offers reproducible criteria for MC cysts and may be used alone for these lesions.     

Salivary gland carcinomas of the larynx: a national study in Denmark

Objective

Salivary gland carcinomas of the larynx are rare. The purpose of this study is to present a national series of laryngeal salivary gland carcinoma patients and to bring a review of recent literature.

Methods

By merging The Danish Cancer Registry, The National Pathology Registry and The National Patient Registry all registered patients with laryngeal salivary carcinomas diagnosed from 1990 to 2007 were identified. The histological slides were reviewed and data concerning age, sex, symptoms, topography, histology, treatment and outcome were registered. Based on a supplemented PubMed search a review of literature from 1991 to 2010 was performed.

Results

Six Danish patients with a malignant salivary gland tumor in the larynx were identified resulting in an incidence of 0.001/100,000 inhabitants/year. Four had adenoid cystic carcinoma and two a mucoepidermoid carcinoma. All patients were male. The patients were treated with surgery and/or radiotherapy. Three patients had recurrent disease. One died of the primary disease and one died of other causes. Four are alive with no evidence of disease. Merging of actual study group with patients from recent literature resulted in 83 cases. The male vs. female ratio was 2:1, the most common location was the supraglottic region (52%) and the most predominant histological subtypes were adenoid cystic carcinoma (46%), mucoepidermoid carcinoma (35%) and adenocarcinoma NOS (12%).

Conclusion

Laryngeal salivary gland carcinoma is a rare disease with a male predominance and most often localized in the supraglottic region. Data concerning treatment and outcome are scarce, but primary surgery with utmost focus on free surgical margins is the treatment of choice. Recurrences are observed later than ten years after primary treatment and a long follow up time is advocated.     

Peptoids that mimic the structure, function, and mechanism of helical antimicrobial peptides

Antimicrobial peptides (AMPs) and their mimics are emerging as promising antibiotic agents. We present a library of "ampetoids" (antimicrobial peptoid oligomers) with helical structures and biomimetic sequences, several members of which have low-micromolar antimicrobial activities, similar to cationic AMPs like pexiganan. Broad-spectrum activity against six clinically relevant BSL2 pathogens is also shown. This comprehensive structure-activity relationship study, including circular dichroism spectroscopy, minimum inhibitory concentration assays, hemolysis and mammalian cell toxicity studies, and specular x-ray reflectivity measurements shows that the in vitro activities of ampetoids are strikingly similar to those of AMPs themselves, suggesting a strong mechanistic analogy. The ampetoids' antibacterial activity, coupled with their low cytotoxicity against mammalian cells, make them a promising class of antimicrobials for biomedical applications. Peptoids are biostable, with a protease-resistant N-substituted glycine backbone, and their sequences are highly tunable, because an extensive diversity of side chains can be incorporated via facile solid-phase synthesis. Our findings add to the growing evidence that nonnatural foldamers will emerge as an important class of therapeutics.     

Platelet‐rich plasma counteracts detrimental effect of high‐glucose concentrations on mesenchymal stem cells from Bichat fat pad

Diabetic patients display increased risk of periodontitis and failure in bone augmentation procedures. Mesenchymal stem cells (MSCs) and platelet‐rich plasma (PRP) represent a relevant advantage in tissue repair process and regenerative medicine. We isolated MSCs from Bichat's buccal fat pad (BFP) and measured the effects of glucose and PRP on cell number and osteogenic differentiation potential. Cells were cultured in the presence of 5.5‐mM glucose (low glucose [LG]) or 25‐mM glucose (high glucose [HG]). BFP–MSC number was significantly lower when cells were cultured in HG compared with those in LG. Following osteogenic differentiation procedures, calcium accumulation, alkaline phosphatase activity, and expression of osteogenic markers were significantly lower in HG compared with LG. Exposure of BFP–MSC to PRP significantly increased cell number and osteogenic differentiation potential, reaching comparable levels in LG and in HG. Thus, high‐glucose concentrations impair BFP–MSC growth and osteogenic differentiation. However, these detrimental effects are largely counteracted by PRP.     

Efficacy of platelet-rich fibrin compared with triamcinolone acetonide as injective therapy in the treatment of symptomatic oral lichen planus: a pilot study

Clinical Oral Investigations - Oral lichen planus (OLP) is a chronic immune-mediated disease that affects the oral cavity. Topical steroids are considered the treatment of choice for painful...     

Ultrafast DNA sequencing on a microchip by a hybrid separation mechanism that gives 600 bases in 6.5 minutes

To realize the immense potential of large-scale genomic sequencing after the completion of the second human genome (Venter's), the costs for the complete sequencing of additional genomes must be dramatically reduced. Among the technologies being developed to reduce sequencing costs, microchip electrophoresis is the only new technology ready to produce the long reads most suitable for the de novo sequencing and assembly of large and complex genomes. Compared with the current paradigm of capillary electrophoresis, microchip systems promise to reduce sequencing costs dramatically by increasing throughput, reducing reagent consumption, and integrating the many steps of the sequencing pipeline onto a single platform. Although capillary-based systems require approximately 70 min to deliver approximately 650 bases of contiguous sequence, we report sequencing up to 600 bases in just 6.5 min by microchip electrophoresis with a unique polymer matrix/adsorbed polymer wall coating combination. This represents a two-thirds reduction in sequencing time over any previously published chip sequencing result, with comparable read length and sequence quality. We hypothesize that these ultrafast long reads on chips can be achieved because the combined polymer system engenders a recently discovered "hybrid" mechanism of DNA electromigration, in which DNA molecules alternate rapidly between repeating through the intact polymer network and disrupting network entanglements to drag polymers through the solution, similar to dsDNA dynamics we observe in single-molecule DNA imaging studies. Most importantly, these results reveal the surprisingly powerful ability of microchip electrophoresis to provide ultrafast Sanger sequencing, which will translate to increased system throughput and reduced costs.     

Human mesenchymal stem cells derived from induced pluripotent stem cells down-regulate NK-cell cytolytic machinery

A major issue in immunosuppressive biotherapy is the use of mesenchymal stem cells (MSCs) that harbor regulatory capacity. However, currently used bone marrow-derived MSCs (BM-MSCs) are short-lived and cannot assure long lasting immunoregulatory function both in vitro and in vivo. Consequently, we have generated MSCs from human induced pluripotent stem (IPS-MSCs) cells that share similar properties with embryonic stem cells (ES-MSCs). Herein, we compared the immunoregulatory properties of ES/IPS-MSCs with those of BM-MSCs and showed, for the first time, that IPS-derived MSCs display remarkable inhibition of NK-cell proliferation and cytolytic function in a similar way to ES-MSCs. Both MSCs disrupt NK-cell cytolytic machinery in the same fashion that BM-MSCs, by down-regulating the expression of different activation markers and ERK1/2 signaling, leading to an impairment to form immunologic synapses with target cells and, therefore, secretion of cytotoxic granules. In addition, they are more resistant than adult BM-MSCs to preactivated NK cells. IPS-MSCs could represent an attractive alternative source of immunoregulatory cells, and their capacity to impair NK-cell cytotoxicity constitutes a complex mechanism to prevent allograft rejection.     

Tubulin Synthesis on Polysomes Isolated from Brain and Leg Muscle of Embryonic Chick

A protein-synthesizing system has been established in vitro, in which tubulin is synthesized on polysomes isolated from brain and leg muscle of embryonic chick. The tubulin synthesized in vitro is characterized by (i) its electrophoretic mobility on sodium dodecyl sulfate-acrylamide gels (brain: 55,000 daltons; leg muscle: 53,000 daltons), and (ii) its ability to function as a microtubular subunit, as judged by its specific ability to participate in at least two polymerization and depolymerization steps in the microtubule assembly system in vitro.     

Public attitudes and opinions toward physicians and dentists infected with bloodborne viruses: results of a national survey

BACKGROUND: There has been no recent assessment of public attitudes and opinions concerning risk of bloodborne virus transmission during health care. METHODS: Seven items in the 2000 annual Healthstyles survey were used to assess current attitudes and opinions about health care providers infected with human immunodeficiency virus (HIV) and the risk of bloodborne virus transmission during health care in a sample of approximately 3000 US households. RESULTS: Of the 2353 respondents, 89% agreed that they want to know whether their doctor or dentist is infected with HIV; 82% agreed that disclosure of HBV or HCV infection in a provider should be mandatory. However, 47% did not believe that HIV-infected doctors were more likely to infect patients than doctors infected with HBV or HCV. Opinions were divided on whether HIV-infected providers should be able to care for patients as long as they use good infection control: only 38% thought that infected providers should be allowed to provide patient care. CONCLUSIONS: These findings suggest that improved public education and risk communication on health care-associated bloodborne infections is needed.     

From the Cover: In-cell thermodynamics and a new role for protein surfaces

There is abundant, physiologically relevant knowledge about protein cores; they are hydrophobic, exquisitely well packed, and nearly all hydrogen bonds are satisfied. An equivalent understanding of protein surfaces has remained elusive because proteins are almost exclusively studied in vitro in simple aqueous solutions. Here, we establish the essential physiological roles played by protein surfaces by measuring the equilibrium thermodynamics and kinetics of protein folding in the complex environment of living Escherichia coli cells, and under physiologically relevant in vitro conditions. Fluorine NMR data on the 7-kDa globular N-terminal SH3 domain of Drosophila signal transduction protein drk (SH3) show that charge–charge interactions are fundamental to protein stability and folding kinetics in cells. Our results contradict predictions from accepted theories of macromolecular crowding and show that cosolutes commonly used to mimic the cellular interior do not yield physiologically relevant information. As such, we provide the foundation for a complete picture of protein chemistry in cells.Classic theories about the effects of complex environments consider only hard-core repulsions (volume exclusion) and so predict entropy-driven protein stabilization (1–3). Here, we use the 7-kDa globular N-terminal SH3 domain of Drosophila signal transduction protein drk (SH3) as a model to test this idea in living cells. SH3 exists in a dynamic equilibrium between the folded state and the unfolded ensemble (4). This two-state behavior (5) is ideal for NMR-based studies of folding. Fluorine labeling (6) of its sole tryptophan leads to only two ¹⁹F resonances (7): one from the folded state, the other from the unfolded ensemble (Fig. 1A). The area under each resonance is proportional to its population, ρ_f and ρ_u, respectively. These populations are used to quantify protein stability via the modified standard state free energy of unfolding,ΔGU,T°′=−RTlnρUρF,[1]where R is the gas constant and T is the absolute temperature. Furthermore, the width at half height of each resonance is proportional to the transverse relaxation rate, which is an approximate measure of intermolecular interactions (8–10). Thus, this simple system yields both quantitative thermodynamic knowledge and information about interactions involving the folded state and the unfolded ensemble.Open in a separate windowFig. 1.Fluorine spectra acquired at 298 K, in buffer (A) and cells (B). The blue trace is from the postexperiment supernatant and shows that the red spectrum arises from protein inside cells. Stability curves (C) in buffer (black), in cells (red and green), and in 100 g/L urea (magenta). In-cell metabolite correction and analysis of uncertainties are discussed in Results and Discussion and Materials and Methods, respectively. Shaded regions are 95% confidence intervals. Error bars for buffer are smaller than the labels and represent the SD of three trials. Error bars for the in-cell data at 273, 298, and 313 K represent the SD of three trials. Stability in buffer (black) and solutions of 100 g/L BSA (blue) and lysozyme (red) at different pH values (D–F). The curve for buffer from C is reproduced in D. The net charges on SH3, BSA, and lysozyme (based on sequence) are shown. Error bars (298 K) represent the SD from three trials. Appearance of new resonances in the pH 3 BSA sample prevented extraction of thermodynamic parameters.To assess the enthalpic (ΔHU°′) and entropic (ΔSU°′) components, we measured the temperature dependence of ΔGU°′. These data were fitted to the integrated Gibbs–Helmholtz equation (11), assuming a constant heat capacity of unfolding, ΔCp,U°:ΔGU,T°′=ΔHU,Tref°′−TΔSU,Tref°′+ΔCp,U°′[T−Tref−T⁡lnTTref],[2]where T_ref is either the melting temperature, T_m (where ρ_f = ρ_u), or the temperature of maximum stability, T_s (where ΔSU°′ = 0) (11).