Reference equivalent threshold sound pressure levels for the Wireless Automated Hearing Test System.

This paper presents reference equivalent threshold sound pressure levels (RETSPLs) for the Wireless Automated Hearing Test System (WAHTS), a recently commercialized device developed for use as a boothless audiometer. Two initial studies were conducted following the ISO 389-9 standard [ISO 389-9 (2009). "Acoustics-Reference zero for the calibration of audiometric equipment. Part 9: Preferred test conditions for the determinations of reference hearing threshold levels" (International Organization for Standardization, Geneva)]. Although the standard recruitment criteria are intended to yield otologically normal test subjects, the recruited populations appeared to have slightly elevated thresholds [5-10 dB hearing level (HL)]. Comparison of WAHTS thresholds to other clinical audiometric equipment revealed bias errors that were consistent with the elevated thresholds of the RETSPL populations. As the objective of RETSPLs is to ensure consistent thresholds regardless of the equipment, this paper presents the RETSPLs initially obtained following ISO 389-9:2009 and suggested correction to account for the elevated HLs of the originally recruited populations. Two additional independent studies demonstrate the validity of these corrected thresholds.

Comparison of Primary Laser Spectroscopy and Mass Spectrometry Methods for Measuring Mass Concentration of Gaseous Elemental Mercury.

We present a direct comparison between two independent methods for the measurement of gaseous elemental mercury (GEM) mass concentration: isotope dilution cold-vapor inductively coupled plasma mass spectrometry (ID-CV-ICP-MS) and laser absorption spectroscopy (LAS). The former technique combined with passive sorbent tube sampling is currently the primary method at NIST for mercury gas standards traceability to the International System of Units (SI). This traceability is achieved via measurements on a mercury-containing reference material. The latter technique has been recently developed at NIST and involves real-time measurements of light attenuation caused by GEM, with SI traceability based in part on the known spontaneous emission lifetime of the probed 6 1S0-6 3P1 intercombination transition of elemental mercury (Hg0). Using a steady-flow Hg0-in-air generator to produce samples measured by both methods, we use LAS to measure the sample gas and in parallel we collect the Hg0 on sorbent tubes to be subsequently analyzed using ID-CV-ICP-MS. Over the examined mass concentration range (41 µg/m3 to 287 µg/m3 Hg0 in air), the relative disagreement between the two approaches ranged from (1.0 to 1.8)%. The relative combined standard uncertainty on average is 0.4% and 0.9%, for the LAS and MS methods, respectively. Our comparison studies help validate the accuracy of the ID-CV-ICP-MS primary method as well as establish the LAS technique as an attractive alternative primary method for SI-traceable measurements of GEM.

Measuring diffusion exchange across the cell membrane with DEXSY (Diffusion Exchange Spectroscopy).

INTRODUCTION: To combine numerical simulations, in vitro and in vivo experiments to evaluate the feasibility of measuring diffusion exchange across the cell membrane with diffusion exchange spectroscopy (DEXSY). METHODS: DEXSY acquisitions were simulated over a range of permeabilities in nerve tissue and yeast substrates. In vitro measurements were performed in a yeast substrate and in vivo measurements in mouse tumor xenograft models, all at 9.4 T. RESULTS: Diffusion exchange was observed in simulations over a physiologically relevant range of cell permeability values. In vitro and in vivo measures also provided evidence of diffusion exchange, which was quantified with the Diffusion Exchange Index (DEI). CONCLUSIONS: Our findings provide preliminary evidence that DEXSY can be used to make in vivo measurements of diffusion exchange and cell membrane permeability.

Inhibition of acid ceramidase regulates MHC class II antigen presentation and suppression of autoimmune arthritis.

The bioactive sphingolipid ceramide affects immune responses although its effect on antigen (Ag) processing and delivery by HLA class II to CD4+T-cells remains unclear. Therefore, we examined the actions of a novel cell-permeable acid ceramidase (AC) inhibitor [(1R,2R) N myristoylamino-(4'-nitrophenyl)-propandiol-1,3] on antigen presentation and inflammatory cytokine production by Ag-presenting cells (APCs) such as B-cells, macrophages, and dendritic cells. We found that AC inhibition in APCs perturbed Ag-processing and presentation via HLA-DR4 (MHC class II) proteins as measured by coculture assay and T-cell production of IL-2. Mass spectral analyses showed that B13 treatment significantly raised levels of four types of ceramides in human B-cells. B13 treatment did not alter Ag internalization and class II protein expression, but significantly inhibited lysosomal cysteinyl cathepsins (B, S and L) and thiol-reductase (GILT), HLA class II Ag-processing, and generation of functional class II-peptide complexes. Ex vivo Ag presentation assays showed that inhibition of AC impaired primary and recall CD4+T-cell responses and cytokine production in response against type II collagen. Further, B13 delayed onset and reduced severity of inflamed joints and cytokine production in the collagen-induced arthritis mouse model in vivo. These findings suggest that inhibition of AC in APCs may dysregulate endolysosomal proteases and HLA class II-associated self-antigen presentation to CD4+T-cells, attenuating inflammatory cytokine production and suppressing host autoimmune responses.

TabSINT: open-source mobile software for distributed studies of hearing.

Objective: The recent emphasis on outcomes-based medical research has motivated a need for technology that allows researchers and clinicians to reach a larger and more diverse subject population for recruitment and testing.Design: This article reports on open-source mobile software (TabSINT) that enables researchers to administer customised hearing tests and questionnaires on tablets located across multiple sites. Researchers create and modify test protocols using text-based templates and deploy it to the tablets via a cloud-based repository or USB-computer connection. Results are exported locally to the tablet SD card and can also be automatically posted to a cloud-based database.Results: Between 2014 and 2019, TabSINT collected 25,000+ test results using more than 200+ unique test protocols for researchers located worldwide.Conclusions:TabSINT is a powerful software system with the potential to greatly enhance research across multiple disciplines by enabling access to subject cohorts in remote and disparate locations. Released open-source, this software is available to researchers across the world to use and adapt to their specific needs. Researchers with engineering resources can contribute to the repository to extend the capability and robustness of this software.

Genetic and pharmacological inhibition of acid ceramidase prevents asymmetric cell division by neosis.

Radiation treatment failure or relapse after initial response to chemotherapy presents significant clinical challenges in cancer patients. Escape from initial courses of treatment can involve reactivation of embryonic developmental stages, with the formation of polynuclear giant cancer cells (PGCCs). This strategy of dedifferentiation can insulate cancer cells from a variety of treatments and allows a residual subpopulation to reestablish tumors after treatment. Using radiation or docetaxel chemotherapy, we generated PGCCs from prostate cancer cells. Here, we show that expression of acid ceramidase (ASAH1), an enzyme in the sphingolipid pathway linked to therapy resistance and poor outcomes, is elevated in PGCCs. Targeting ASAH1 with shRNA or treatment with the ASAH1 inhibitor, LCL-521, did not impair the formation of PGCCs, but prevented the formation of PGCC progeny that arise through an asymmetric cell division called neosis. Similar results were obtained in lung cancer cells that had been exposed to radiation or cisplatin chemotherapy as stressors. In summary, our data suggest that endoreplication occurs independent of ASAH1 while neosis is ASAH1-dependent in both prostate and lung cancer cells. Because ASAH1 knockout is embryonic lethal but not deleterious to adult animals, targeting this enzyme has the potential to be highly specific to cells undergoing the dedifferentiation process to escape cancer treatments. Pharmacological inhibition of ASAH1 is a potentially powerful strategy to eliminate cells that could otherwise serve as seed populations for recurrence.

The systematics of Lobophora (Dictyotales, Phaeophyceae) in the western Atlantic and eastern Pacific oceans: eight new species.

Lobophora is a common tropical to temperate genus of brown algae found in a plethora of habitats including shallow and deep-water coral reefs, rocky shores, mangroves, seagrass beds, and rhodoliths beds. Recent molecular studies have revealed that Lobophora species diversity has been severely underestimated. Current estimates of the species numbers range from 100 to 140 species with a suggested center of diversity in the Central Indo-Pacific. This study used three molecular markers (cox3, rbcL, psbA), different single-marker species delimitation methods (GMYC, ABGD, PTP), and morphological evidence to evaluate Lobophora species diversity in the Western Atlantic and the Eastern Pacific oceans. Cox3 provided the greatest number of primary species hypotheses(PSH), followed by rbcL and then psbA. GMYC species delimitation analysis was the most conservative across all three markers, followed by PTP, and then ABGD. The most informative diagnostic morphological characters were thallus thickness and number of cell layers in both the medulla and the dorsal/ventral cortices. Following a consensus approach, 14 distinct Lobophora species were identified in the Western Atlantic and five in the Eastern Pacific. Eight new species from these two oceans were herein described: L. adpressa sp. nov., L. cocoensis sp. nov., L. colombiana sp. nov., L. crispata sp. nov., L. delicata sp. nov., L. dispersa sp. nov., L. panamensis sp. nov., and L. tortugensis sp. nov. This study showed that the best approach to confidently identify Lobophora species is to analyze DNA sequences (preferably cox3 and rbcL) followed by comparative morphological and geographical assessment.

Siderophore-Antibiotic Conjugate Design: New Drugs for Bad Bugs?

Antibiotic resistance is a global health concern and a current threat to modern medicine and society. New strategies for antibiotic drug design and delivery offer a glimmer of hope in a currently limited pipeline of new antibiotics. One strategy involves conjugating iron-chelating microbial siderophores to an antibiotic or antimicrobial agent to enhance uptake and antibacterial potency. Cefiderocol (S-649266) is a promising cephalosporin-catechol conjugate currently in phase III clinical trials that utilizes iron-mediated active transport and demonstrates enhanced potency against multi-drug resistant (MDR) Gram-negative pathogens. Such molecules demonstrate that siderophore-antibiotic conjugates could be important future medicines to add to our antibiotic arsenal. This review is written in the context of the chemical design of siderophore-antibiotic conjugates focusing on the differing siderophore, linker, and antibiotic components that make up conjugates. We selected chemically distinct siderophore-antibiotic conjugates as exemplary conjugates, rather than multiple analogues, to highlight findings to date. The review should offer a general guide to the uninitiated in the molecular design of siderophore-antibiotic conjugates.

NIST Standards for Measurement, Instrument Calibration, and Quantification of Gaseous Atmospheric Compounds.

There are many gas phase compounds present in the atmosphere that affect and influence the earth's climate. These compounds absorb and emit radiation, a process which is the fundamental cause of the greenhouse effect. The major greenhouse gases in the earth's atmosphere are carbon dioxide, methane, nitrous oxide, and ozone. Some halocarbons are also strong greenhouse gases and are linked to stratospheric ozone depletion. Hydrocarbons and monoterpenes are precursors and contributors to atmospheric photochemical processes, which lead to the formation of particulates and secondary photo-oxidants such as ozone, leading to photochemical smog. Reactive gases such as nitric oxide and sulfur dioxide are also compounds found in the atmosphere and generally lead to the formation of other oxides. These compounds can be oxidized in the air to acidic and corrosive gases and contribute to photochemical smog. Measurements of these compounds in the atmosphere have been ongoing for decades to track growth rates and assist in curbing emissions of these compounds into the atmosphere. To accurately establish mole fraction trends and assess the role of these gas phase compounds in atmospheric chemistry, it is essential to have good calibration standards. The National Institute of Standards and Technology has been developing standards of many of these compounds for over 40 years. This paper discusses the development of these standards.

Talk CPR - a technology project to improve communication in do not attempt cardiopulmonary resuscitation decisions in palliative illness.

BACKGROUND: A national Do Not Attempt Cardiopulmonary Resuscitation policy was rolled out for the National Health Service in Wales in 2015. A national steering group led on producing information videos and a website for patients, carers and healthcare professionals, forming part of a quality improvement program. Videos were planned, scripted and produced with healthcare professionals and patient/carer representatives, and were completed with both English and Welsh language versions. The TalkCPR videos encourage and promote open discussion about Cardiopulmonary Resuscitation (CPR) and DNACPR in palliative care situations. METHODS: We worked with patient/carer groups to evaluate whether video resources to convey the salient facts involved in CPR and DNACPR decisions for people with palliative and life-limiting illness were acceptable or not. We conducted a mixed-method design service review in five phases to evaluate whether this technological resource could help. After creating video and website materials, they were evaluated by doctors, nurses and a patient/carer group. We also sent out one lightweight TalkCPR video media pad to each practice in Wales. These rechargeable electronic video media pads had communication videos pre-loaded for easy viewing, especially in areas with poor roaming data coverage. RESULTS: Videos were demonstrably acceptable to both patient and carer groups, and improved healthcare professional confidence and understanding. Videos went live on the TalkCPR website, in all Welsh Health Boards and on Youtube, and are now used in routine practice throughout Wales. CONCLUSION: This is the first time that DNACPR information videos are aimed directly at palliative care patients and carers, to explore this sensitive subject with them, and to encourage them to approach their doctor or nurse about it. The website, app and video media pads were developed by patients, the Digital Legacy Association, Welsh NHS IT services, Welsh Government, the Bevan Commission and the Dying Matters Charity in Wales 'Byw Nawr'. The GMC, the Royal College of General Practitioners and NICE have listed TalkCPR as a learning resource. There has also been a collaboration with Falmouth University Art College, who helped produce graphic designs to facilitate and encourage discussions about CPR and end of life care.

The design and synthesis of an antibacterial phenothiazine-siderophore conjugate.

Siderophore-antibiotic conjugates consist of an antibiotic covalently linked by a tether to a siderophore. Such conjugates can demonstrate enhanced uptake and internalisation to the bacterial cell resulting in significantly reduced MIC values and extended spectrum of activity. Phenothiazines are a class of small molecules that have been identified as a potential treatment for multidrug resistant tuberculosis and latent TB. Herein we report the design and synthesis of the first phenothiazine-siderophore conjugate. A convergent synthetic route was developed whereby the functionalised phenothiazine component was prepared in four steps and the siderophore component also prepared in four steps. In M. smegmatis the functionalised phenothiazine demonstrated an equipotent MIC value in direct comparison to the parent phenothiazine from which it was derived. The final conjugate was synthesised by amide bond formation between the two components and global deprotection of the PMB protecting groups to unmask the catechol iron chelating groups of the siderophore. The synthesis is readily amenable to the preparation of analogues whereby the siderophore component of the conjugate can be modified. The route will be used to prepare a library of siderophore-phenothiazine conjugates for full biological evaluation of much needed new antibacterial agents.

Acid Ceramidase Deficiency is characterized by a unique plasma cytokine and ceramide profile that is altered by therapy.

Acid Ceramidase Deficiency (Farber disease, FD) is an ultra-rare Lysosomal Storage Disorder that is poorly understood and often misdiagnosed as Juvenile Idiopathic Arthritis (JIA). Hallmarks of FD are accumulation of ceramides, widespread macrophage infiltration, splenomegaly, and lymphocytosis. The cytokines involved in this abnormal hematopoietic state are unknown. There are dozens of ceramide species and derivatives, but the specific ones that accumulate in FD have not been investigated. We used a multiplex assay to analyze cytokines and mass spectrometry to analyze ceramides in plasma from patients and mice with FD, controls, Farber patients treated by hematopoietic stem cell transplantation (HSCT), JIA patients, and patients with Gaucher disease. KC, MIP-1α, and MCP-1 were sequentially upregulated in plasma from FD mice. MCP-1, IL-10, IL-6, IL-12, and VEGF levels were elevated in plasma from Farber patients but not in control or JIA patients. C16-Ceramide (C16-Cer) and dhC16-Cer were upregulated in plasma from FD mice. a-OH-C18-Cer, dhC12-Cer, dhC24:1-Cer, and C22:1-Cer-1P accumulated in plasma from patients with FD. Most cytokines and only a-OH-C18-Cer returned to baseline levels in HSCT-treated Farber patients. Sphingosines were not altered. Chitotriosidase activity was also relatively low. A unique cytokine and ceramide profile was seen in the plasma of Farber patients that was not observed in plasma from HSCT-treated Farber patients, JIA patients, or Gaucher patients. The cytokine profile can potentially be used to prevent misdiagnosis of Farber as JIA and to monitor the response to treatment. Further understanding of why these signaling molecules and lipids are elevated can lead to better understanding of the etiology and pathophysiology of FD and inform development of future treatments.

Effects of supervised exercise and dietary nitrate in older adults with controlled hypertension and/or heart failure with preserved ejection fraction.

Aerobic exercise training is an effective therapy to improve peak aerobic power (peak VO2) in individuals with hypertension (HTN, AHA/ACC class A) and heart failure patients with preserved ejection fraction (HFpEF). High nitrate containing beetroot juice (BRJ) also improves sub-maximal endurance and decreases blood pressure in both HTN and HFpEF. We hypothesized that combining an aerobic exercise and dietary nitrate intervention would result in additive or even synergistic positive effects on exercise tolerance and blood pressure in HTN or HFpEF. We report results from two pilot studies examining the effects of supervised aerobic exercise combined with dietary nitrate in patients with controlled HTN (n = 26, average age 65 ± 5 years) and in patients with HFpEF (n = 20, average age 69 ± 7 years). All patients underwent an aerobic exercise training regimen; half were randomly assigned to consume a high nitrate-containing beet juice beverage (BRJ containing 6.1 mmol nitrate for the HFpEF study consumed three times a week and 8 mmol nitrate for the HTN study consumed daily) while the other half consumed a beet juice beverage with the nitrate removed (placebo). The main result was that there was no added benefit observed for any outcomes when comparing BRJ to placebo in either HTN or HFpEF patients undergoing exercise training (p ≥ 0.14). There were within-group benefits. In the pilot study in patients with HFpEF, aerobic endurance (primary outcome), defined as the exercise time to volitional exhaustion during submaximal cycling at 75% of maximal power output, improved during exercise training within each group from baseline to end of study, 369 ± 149 s vs 520 ± 257 s (p = 0.04) for the placebo group and 384 ± 129 s vs 483 ± 258 s for the BRJ group (p = 0.15). Resting systolic blood pressure in patients with HFpEF also improved during exercise training in both groups, 136 ± 16 mm Hg vs 122 ± 3 mm Hg for the placebo group (p < 0.05) and 132 ± 12 mm Hg vs 119 ± 9 mm Hg for the BRJ group (p < 0.05). In the HTN pilot study, during a treadmill graded exercise test, peak oxygen consumption (primary outcome) did not change significantly, but time to exhaustion (also a primary outcome) improved in both groups, 504 ± 32 s vs 601 ± 38 s (p < 0.05) for the placebo group and 690 ± 38 s vs 772 ± 95 s for the BRJ group (p < 0.05) which was associated with a reduction in supine resting systolic blood pressure in BRJ group. Arterial compliance also improved during aerobic exercise training in both the HFpEF and the HTN patients for both BRJ and placebo groups. Future work is needed to determine if larger nitrate doses would provide an added benefit to supervised aerobic exercise in HTN and HFpEF patients.

Targeting (cellular) lysosomal acid ceramidase by B13: design, synthesis and evaluation of novel DMG-B13 ester prodrugs.

Acid ceramidase (ACDase) is being recognized as a therapeutic target for cancer. B13 represents a moderate inhibitor of ACDase. The present study concentrates on the lysosomal targeting of B13 via its N,N-dimethylglycine (DMG) esters (DMG-B13 prodrugs). Novel analogs, the isomeric mono-DMG-B13, LCL522 (3-O-DMG-B13·HCl) and LCL596 (1-O-DMG-B13·HCl) and di-DMG-B13, LCL521 (1,3-O, O-DMG-B13·2HCl) conjugates, were designed and synthesized through N,N-dimethyl glycine (DMG) esterification of the hydroxyl groups of B13. In MCF7 cells, DMG-B13 prodrugs were efficiently metabolized to B13. The early inhibitory effect of DMG-B13 prodrugs on cellular ceramidases was ACDase specific by their lysosomal targeting. The corresponding dramatic decrease of cellular Sph (80-97% Control/1h) by DMG-B13 prodrugs was mainly from the inhibition of the lysosomal ACDase.

LCL124, a cationic analog of ceramide, selectively induces pancreatic cancer cell death by accumulating in mitochondria.

Treatment of pancreatic cancer that cannot be surgically resected currently relies on minimally beneficial cytotoxic chemotherapy with gemcitabine. As the fourth leading cause of cancer-related death in the United States with dismal survival statistics, pancreatic cancer demands new and more effective treatment approaches. Resistance to gemcitabine is nearly universal and appears to involve defects in the intrinsic/mitochondrial apoptotic pathway. The bioactive sphingolipid ceramide is a critical mediator of apoptosis initiated by a number of therapeutic modalities. It is noteworthy that insufficient ceramide accumulation has been linked to gemcitabine resistance in multiple cancer types, including pancreatic cancer. Taking advantage of the fact that cancer cells frequently have more negatively charged mitochondria, we investigated a means to circumvent resistance to gemcitabine by targeting delivery of a cationic ceramide (l-t-C6-CCPS [LCL124: ((2S,3S,4E)-2-N-[6'-(1″-pyridinium)-hexanoyl-sphingosine bromide)]) to cancer cell mitochondria. LCL124 was effective in initiating apoptosis by causing mitochondrial depolarization in pancreatic cancer cells but demonstrated significantly less activity against nonmalignant pancreatic ductal epithelial cells. Furthermore, we demonstrate that the mitochondrial membrane potentials of the cancer cells were more negative than nonmalignant cells and that dissipation of this potential abrogated cell killing by LCL124, establishing that the effectiveness of this compound is potential-dependent. LCL124 selectively accumulated in and inhibited the growth of xenografts in vivo, confirming the tumor selectivity and therapeutic potential of cationic ceramides in pancreatic cancer. It is noteworthy that gemcitabine-resistant pancreatic cancer cells became more sensitive to subsequent treatment with LCL124, suggesting that this compound may be a uniquely suited to overcome gemcitabine resistance in pancreatic cancer.

Temperature measurement and optical path-length bias improvement modifications to National Institute of Standards and Technology ozone reference standards.

UNLABELLED: Ambient ozone measurements in the United States and many other countries are traceable to a National Institute of Standards and Technology Standard Reference Photometer (NIST SRP). The NIST SRP serves as the highest level ozone reference standard in the United States, with NIST SRPs located at NIST and at many U.S. Environmental Protection Agency (EPA) laboratories. The International Bureau of Weights and Measures (BIPM) maintains a NIST SRP as the reference standard for international measurement comparability through the International Committee of Weights and Measures (CIPM). In total, there are currently NIST SRPs located in 20 countries for use as an ozone reference standard. A detailed examination of the NIST SRP by the BIPM and NIST has revealed a temperature gradient and optical path-length bias inherent in all NIST SRPs. A temperature gradient along the absorption cells causes incorrect temperature measurements by as much as 2 degrees C. Additionally, the temperature probe used for temperature measurements was found to inaccurately measure the temperature of the sample gas due to a self-heating effect. Multiple internal reflections within the absorption cells produce an actual path length longer than the measured fixed length used in the calculations for ozone mole fractions. Reflections from optical filters located at the exit of the absorption cells add to this effect. Because all NIST SRPs are essentially identical, the temperature and path-length biases exist on all units by varying amounts dependent upon instrument settings, laboratory conditions, and absorption cell window alignment. This paper will discuss the cause of and physical modifications for reducing these measurement biases in NIST SRPs. Results from actual NIST SRP bias upgrades quantifying the effects of these measurement biases on ozone measurements are summarized. IMPLICATIONS: NIST SRPs are maintained in laboratories around the world underpinning ozone measurement calibration and traceability within and between countries. The work described in this paper quantifies and shows the reduction of instrument biases in NIST SRPs improving their overall agreement. This improved agreement in all NIST SRPs provides a more stable baseline for ozone measurements worldwide.

Bayesian probabilistic network modeling from multiple independent replicates.

Often protein (or gene) time-course data are collected for multiple replicates. Each replicate generally has sparse data with the number of time points being less than the number of proteins. Usually each replicate is modeled separately. However, here all the information in each of the replicates is used to make a composite inference about signal networks. The composite inference comes from combining well structured Bayesian probabilistic modeling with a multi-faceted Markov Chain Monte Carlo algorithm. Based on simulations which investigate many different types of network interactions and experimental variabilities, the composite examination uncovers many important relationships within the networks. In particular, when the edge's partial correlation between two proteins is at least moderate, then the composite's posterior probability is large.

Differential expression of epithelial and mesenchymal proteins in a panel of prostate cancer cell lines.

PURPOSE: Epithelial to mesenchymal transition is an important process that results in increased cell migration, invasion and metastasis of many carcinomas. During epithelial to mesenchymal transition epithelial cells down-regulate cell-cell adhesion molecules (ie E-cadherin), up-regulate mesenchymal proteins (ie N-cadherin and cadherin-11), alter polarity, reorganize the cytoskeleton and become isolated. In combination this leads to greater motility. We investigated the role of E-cadherin and the associated catenin-protein complex in regulating epithelial to mesenchymal transition in prostate cancer progression. MATERIALS AND METHODS: The relative invasion index of prostate cancer cells was assessed by MTT based in vitro invasion assay. Immunoprecipitation and Western blot were done to determine cadherin-complex formation, and catenin and cadherin protein expression. RESULTS: Restoration of E-cadherin expression in nonE-cadherin expressing prostate cancer cells decreased invasive potential. However, in vitro invasive potential was tightly regulated by the interaction of cadherin proteins with the catenin complex. E and N-cadherin, cadherin-11, and the catenin proteins α, ß, γ and p120 are important for the downstream signaling associated with epithelial to mesenchymal transition in tumor cells. CONCLUSIONS: Restoration of epithelial specific proteins, such as E-cadherin, in tumor cells can inhibit invasion. However, invasion is a complex process regulated not only by E and N-cadherin but also by catenin-complex proteins. The complex signaling process associated with tumor invasion warrants further investigation since crosstalk between overlapping signaling pathways is involved in regulating prostate cancer invasion, metastasis and progression.

Power of food moderates food craving, perceived control, and brain networks following a short-term post-absorptive state in older adults.

The Power of Food Scale (PFS) is a new measure that assesses the drive to consume highly palatable food in an obesogenic food environment. The data reported in this investigation evaluate whether the PFS moderates state cravings, control beliefs, and brain networks of older, obese adults following either a short-term post-absorptive state, in which participants were only allowed to consume water, or a short-term energy surfeit treatment condition, in which they consumed BOOST®. We found that the short-term post-absorptive condition, in which participants consumed water only, was associated with increases in state cravings for desired food, a reduction in participants' confidence related to the control of eating behavior, and shifts in brain networks that parallel what is observed with other addictive behaviors. Furthermore, individuals who scored high on the PFS were at an increased risk for experiencing these effects. Future research is needed to examine the eating behavior of persons who score high on the PFS and to develop interventions that directly target food cravings.

Multicenter, retrospective comparison of implant survival, complications and cost between plate and screw and intramedullary nail fixation for metastatic lesions of the diaphyseal humerus.

Background: The humerus is a common site of metastatic disease that can be fixated with either plate and screw or intramedullary nail (IMN) constructs. A multicenter retrospective comparison study was undertaken to compare implant survival, complication rate and cost between the two constructs. No prior studies have included a cost comparison. Methods: Databases of two academic practices were queried retrospectively to identify patients with metastases of the humerus. Inclusion criteria were a lesion in the proximal metaphysis to distal diaphysis and amenable to both implant options with available cost data. Follow-up was at least 6 months barring death or discharge to hospice sooner. Demographic, clinical and outcome data was recorded. Costs were estimated based on contract pricing. Operating room (OR) costs were estimated using per minute OR costs proposed by other investigators. Results: One hundred and one humeri in 96 patients were included (72 plates and 29 nails). The most common malignancies were renal cell, myeloma and lung. Half presented with a displaced fracture. Demographics were similar in both groups. Lesions were larger in the plate group. Surgical times were longer in the plate group, 146 vs. 75 min, P<0.001. Estimated blood loss (EBL) was higher in the plate group, 510 vs. 221 mL, P<0.001. A trend toward increased failure was seen in the plate group, 12.5% vs. 0% (P=0.056). The most common complications in the plate group were pain, stiffness and swelling compared to pain, refracture and PE in the nail group. Local disease progression was equivalent. Implant costs were higher in the IMN group ($2,753 vs. $1,553, P<0.001), while OR costs were lower ($2,349 vs. $4,395, P<0.001). Overall cost of implantation was lower in the IMN group ($5,102 vs. $5,949, P=0.005). Conclusions: IMN of metastases of the humerus offers a faster, potentially more durable construct with lower blood loss, faster OR times and decreased cost of implantation.