Search

Switching intention can significantly lead to customer switching, which severely damages a service firm’s number of customers and profits. Thus, the objective of this research was to help bank managers identify the significant factors regarding switching intention by examining the impacts of convenience, price, perceived value and customer satisfaction, as well as their complex relationships with switching intention. Self-administered questionnaires were used in this study to collect data from 323 banking customers in Phnom Penh, Cambodia. Furthermore, path analysis was used since it has the ability to extend multiple regressions within a framework that has more complex relationships. Hence, results firstly indicate that convenience and price significantly influenced perceived value and customer satisfaction. Next, perceived value significantly influenced customer satisfaction. Finally, customer satisfaction and price significantly influenced switching intention. The results of this paper provide suggestions as well as solutions to bank managers, for example, how to design an appropriate strategy for adjusting a reasonable price setting, and how to provide convenience in order to enhance value and satisfaction; thus, future switching propensities can be minimized.

The AMoRE-II experiment will search for the 0νββ decay of 100Mo nuclei using molybdate crystal scintillators, operating at milli-Kelvin (mK) temperatures, with a total of 80 kg of 100Mo. The background goal for the experiment is 10–4 counts/keV/kg/year in the region of interest around the 0νββ decay Q-value of 3,034 keV. To achieve this level, the rate of background signals arising from emissions produced by decays of radioactive impurities in the detector and shielding materials must be strictly controlled. To do this, concentrations of such impurities are measured and are controlled through materials selection and purification. In this paper, we describe the design and the construction materials used to build the AMoRE-II detector and shielding system, including active and passive shielding, the cryostat, and the detector holders and instrumentation, and we report on measurements of radioactive impurities within candidate and selected materials.

Abstract The Advanced Mo-based Rare process Experiment (AMoRE)-Pilot experiment is an initial phase of the AMoRE search for neutrinoless double beta decay of $$^{100}$$ 100 Mo, with the purpose of investigating the level and sources of backgrounds. Searches for neutrinoless double beta decay generally require ultimately low backgrounds. Surface $$\alpha $$ α decays on the crystals themselves or nearby materials can deposit a continuum of energies that can be as high as the Q-value of the decay itself and may fall in the region of interest (ROI). To understand these background events, we studied backgrounds from radioactive contaminations internal to and on the surface of the crystals or nearby materials with Geant4-based Monte Carlo simulations. In this study, we report on the measured $$\alpha $$ α energy spectra fitted with the corresponding simulated spectra for six crystal detectors, where sources of background contributions could be identified through high energy $$\alpha $$ α peaks and continuum parts in the energy spectrum for both internal and surface contaminations. We determine the low-energy contributions from internal and surface $$\alpha $$ α contaminations by extrapolating from the $$\alpha $$ α background fitting model.

Abstract Background The number of patients suffering from osteoporosis is increasing as the elderly population increases. The demand for investigating bone regeneration strategies naturally arises. One of the approaches to induce bone regeneration is somatic cell transdifferentiation. Among the transcriptional regulators for transdifferentiation, octamer-binding transcription factor 4 (OCT4) is famous for its role in the regulation of pluripotency of stem cells. Bone morphogenetic protein 4 (BMP4) is another factor that is known to have a significant role in osteogenic differentiation. Previous studies have achieved transdifferentiation of cells into osteoblasts using viral and plasmid deliveries of these factors. Although these methods are efficient, viral and plasmid transfection have safety issues such as permanent gene incorporations and bacterial DNA insertions. Herein, we developed a cell penetrating protein-based strategy to induce transdifferentiation of endothelial cells into osteoblasts via nuclear delivery of OCT4 recombinant protein combined with the BMP4 treatment. For the nuclear delivery of OCT4 protein, we fused the protein with 30Kc19, a cell-penetrating and protein stabilizing protein derived from a silkworm hemolymph of Bombyx mori with low cytotoxic properties. This study proposes a promising cell-based therapy without any safety issues that existing transdifferentiation approaches had. Methods OCT4-30Kc19 protein with high penetrating activities and stability was synthesized for a protein-based osteogenic transdifferentiation system. Cells were treated with OCT4-30Kc19 and BMP4 to evaluate their cellular penetrating activity, cytotoxicity, osteogenic and angiogenic potentials in vitro. The osteogenic potential of 3D cell spheroids was also analyzed. In addition, in vivo cell delivery into subcutaneous tissue and cranial defect model was performed. Results OCT4-30Kc19 protein was produced in a soluble and stable form. OCT4-30Kc19 efficiently penetrated cells and were localized in intracellular compartments and the nucleus. Cells delivered with OCT4-30Kc19 protein combined with BMP4 showed increased osteogenesis, both in 2D and 3D culture, and showed increased angiogenesis capacity in vitro. Results from in vivo subcutaneous tissue delivery of cell-seeded scaffolds confirmed enhanced osteogenic properties of transdifferentiated HUVECs via treatment with both OCT4-30Kc19 and BMP4. In addition, in vivo mouse cranial defect experiment demonstrated successful bone regeneration of HUVECs pretreated with both OCT4-30Kc19 and BMP4. Conclusions Using a protein-based transdifferentiation method allows an alternative approach without utilizing any genetic modification strategies, thus providing a possibility for safer use of cell-based therapies in clinical applications.

Here the authors demonstrate the use of zinc isotopes (δ66Zn) to geochemically assess trophic levels in extant and extinct sharks. They show that the Neogene megatooth shark (Otodus megalodon) and the great white shark (Carcharodon carcharias) occupied a similar trophic level.

Abstract Polyelectrolyte microcapsules can be applied as microcontainers for the delivery of a wide range of substances, and it is important to search for new methods for capsule destruction and releasing substances from them. In this work, we studied the possibility of using sodium dodecyl sulfonate (SDS) for the release of fluorescein isothiocyanate—dextran from six-layer microcapsules composed of PAH and PSS. It was shown that the presence of SDS in the medium, at a concentration of 3000 μg/ml, leads to the destruction of polyelectrolyte microcapsules and the release of the substance from them (54% of the amount of the encapsulated substance), while the main part of the FITC-dextran released during the first hours of incubation. At an SDS concentration of 100 μg/ml, the substance released is uniform and is 44% in 24 h. At SDS concentrations from 50 to 100 μg/ml, the process of destruction of microcapsules proceeds more slowly. At SDS concentrations from 10 to 50 μg/ml, microcapsules are not degraded.

Controlled release of substance from polyelectrolyte microcapsules is a triggered degradation of the microcapsule membrane that is extensive enough to release the contained substances out into the environment. Membrane degradation can be a result of enzymatic digestion, ultrasound or light exposure, heating, application of a magnetic field, pH or ionic strength changes in the solution or bacteria-mediated processes. This technology can be used for the targeted release of drugs, and for the development of self-healing materials and new generation pesticides.

Abstract Sodium dodecyl sulfate (SDS) is the most widely used anionic surfactant. Its frequent use causes environmental pollution and negative effects on living organisms (even at low concentrations ≈ 20 μg/ml). Thus, cheap and fast methods are needed to detect this surfactant in wastewater and surface waters in order to prevent the negative effects of SDS on the environment and human beings. We discovered that sodium dodecyl sulfate is capable of destroying polyelectrolyte microcapsules, which has been demonstrated by the number of sedimented polyelectrolyte microcapsules (PMC) before and after incubation in SDS solution. Therefore, it was proposed to use PMCs to create qualitative and quantitative diagnostic systems for the determination of SDS in solution. The qualitative system is a polyelectrolyte microcapsules containing polyallylamine labeled with a fluorescent dye—FITC. An excess SDS concentration of more than 5 μg/ml in the analyzed medium leads to the destruction of PMC and an increase in the fluorescence intensity of the solution, which is recorded by a fluorometer. The quantitative diagnostic system is based on turbidimetry of the PMC suspension before and after incubation in an anionic surfactant solution. This system has a range of detectable SDS concentrations from 10 to 50 μg/ml, with a standard deviation of no more than 11%.

Although conventional optical physical unclonable functions (PUFs) are attractive for security applications, existing optical PUFs have inherent complexity. Here, the authors report a low-cost, lens-free and compact optical PUF that uses silk microfiber-based stochastic diffraction.

Abstract Stable oxygen isotope (δ18O) compositions from vertebrate tooth enamel are widely used as biogeochemical proxies for paleoclimate. However, the utility of enamel oxygen isotope values for environmental reconstruction varies among species. Herein, we evaluate the use of stable oxygen isotope compositions from pronghorn (Antilocapra americana Gray, 1866) enamel for reconstructing paleoclimate seasonality, an elusive but important parameter for understanding past ecosystems. We serially sampled the lower third molars of recent adult pronghorn from Wyoming for δ18O in phosphate (δ18OPO4) and compared patterns to interpolated and measured yearly variation in environmental waters as well as from sagebrush leaves, lakes, and rivers (δ18Ow). As expected, the oxygen isotope compositions of phosphate from pronghorn enamel are enriched in 18O relative to environmental waters. For a more direct comparison, we converted δ18Ow values into expected δ18OPO4* values (δ18OW‐PO4*). Pronghorn δ18OPO4 values from tooth enamel record nearly the full amplitude of seasonal variation from Wyoming δ18OW‐PO4* values. Furthermore, pronghorn enamel δ18OPO4 values are more similar to modeled δ18OW‐PO4* values from plant leaf waters than meteoric waters, suggesting that they obtain much of their water from evaporated plant waters. Collectively, our findings establish that seasonality in source water is reliably reflected in pronghorn enamel, providing the basis for exploring changes in the amplitude of seasonality of ancient climates. As a preliminary test, we sampled historical pronghorn specimens (1720 ± 100 AD), which show a mean decrease (a shift to lower values) of 1–2‰ in δ18OPO4 compared to the modern specimens. They also exhibit an increase in the δ18O amplitude, representing an increase in seasonality. We suggest that the cooler mean annual and summer temperatures typical of the 18th century, as well as enhanced periods of drought, drove differences among the modern and historical pronghorn, further establishing pronghorn enamel as excellent sources of paleoclimate proxy data.

Background: Walch B2 glenoid morphology with glenohumeral osteoarthritis is a difficult degenerative pattern to manage for shoulder surgeons. Anatomic total shoulder arthroplasty (TSA) in combination with eccentric reaming or bone grafting are the traditional methods of treatment. Newer approaches such as TSA with posteriorly augmented glenoid components and reverse shoulder arthroplasty (RSA) may offer better stability for the posteriorly subluxated biconcave B2 wear pattern. The aim of this systematic review is to compare mid-term surgical and functional outcomes of Walch B2 glenoids without significant rotator cuff pathology treated with TSA and RSA. Methods: The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by searching the MEDLINE (PubMed) and Embase (Elsevier) databases. Inclusion criteria were clinical studies that evaluated the outcomes and complications of TSA or RSA in the setting of B2 glenoid morphology without significant rotator cuff pathology. Data relevant to TSA and RSA surgical outcomes were extracted and compiled, and outcomes were compared. A meta-analysis of proportions of complication and revision rates among TSA and RSA groups was performed. Results: Overall, 16 articles were included with 414 TSAs and 78 RSAs. The average follow-up duration was 54.1 ± 14.8 months for patients undergoing TSA and 44.8 ± 10.1 months for patients undergoing RSA. The TSA group was further subdivided based on the use of eccentric reaming (135 TSAs), an augmented glenoid component (84 TSAs), or bone grafting (11 TSAs) or was unspecified (184 TSAs). Overall, patients undergoing TSA and RSA demonstrated mean improvements of 50.1 ± 8.5° and 64.7 ± 5.2° in active flexion, 58.5 ± 10.3° and 68.9 ± not reported° in active abduction, and 31.3 ± 5.7° and 29.0 ± 10.2° in active external rotation, respectively. In regard to functional outcome scores, patients undergoing TSA and RSA showed mean Constant score improvements of 38.8 ± 5.3 and 46.6 ± 3.1 points and American Shoulder and Elbow Surgeons score improvements of 48.2 ± 1.0 and 49.2 ± 25.3 points, respectively. Results of the meta-analysis with mid-term follow-up data demonstrated pooled complication rates of 9% (95% confidence interval [CI], 1%-22%) for TSA and 6% (95% CI, 0%-28%) for RSA and pooled revision rates of 2% (95% CI, 0%-8%) for TSA and 1% (95% CI, 0%-15%) for RSA. Conclusion: In the setting of Walch B2 glenoid morphology, TSA with eccentric reaming or an augmented component yields comparable outcomes to RSA. Based on the patient’s age, activity level, and expectations, both TSA and RSA can be considered a reasonable option to treat Walch B2 glenoid morphology.

Introduction: Gender-affirming peritoneal vaginoplasty has been described, and previous descriptions are modifications of the Davydov technique. Aim: To describe our alternative technique for gender-affirming peritoneal vaginoplasty (PV) using a single-pedicled, urachus-peritoneal hinge flap, discussing proposed advantages. Methods: Retrospective review of all consecutive transfeminine patients with neovaginal shortening after prior penile inversion vaginoplasty (PIV) who underwent our PV technique from May 2019 to July 2022. PV was performed via combined transperineal and laparoscopic (robot-assisted) approaches. After spatulation of the neovaginal remnant, a midline, inferiorly based urachus-peritoneal hinge flap was elevated craniocaudally from the umbilicus to the mid-posterior bladder. The free end of the flap was flipped posteriorly and sutured to posterior edge of the open canal remnant, forming a peritoneal pouch. The lateral edges of the pouch were sutured together for water-tight closure. Patients resumed dilation on POD 6 and douching on POD 10. Main Outcome Measures: Ten transfeminine patients underwent PV, with good outcomes. We measured: Pre-op penile and scrotal skin lengths, intra-op tubularized scrotal skin length, pre and post-op vaginal depth and width (immediate and at last follow-up). Results: Pre-op: mean neovaginal depth was 9.2cm (SD 1.5); width was 12cm. Immediate post-op: mean depth was 15.1 cm (SD 2.2 cm, mean net increase: 5.9 cm). At mean follow-up of 18.3 months, mean depth was 12.5 cm (SD 2.1 cm, mean net increase: 3.3 cm) and width was 12 cm. There were no immediate post-op complications. Eight (80%) of the 10 patients report satisfactory vaginal receptive intercourse. The other 2 have not yet attempted vaginal receptive intercourse. Clinical Implications: Advantages of the proposed technique over existing techniques include no tension on peritoneal suture lines and total exclusion of the rectum. Strengths and Limitations: Strengths include a short learning curve for urologic surgeons with robotic experience. The study is limited by small sample size. Conclusions: Our PV technique is a safe and effective option for salvage peritoneal vaginoplasty after primary PIV.Smith SM, Yuan N, Stelmar J, et al. An Alternative Option for Gender-Affirming Revision Vaginoplasty: The Tubularized Urachus-Peritoneal Hinge Flap. Sex Med 2022;10:100572.

Underground mining operations are connected with significant risks of technogenic accidents, which can be catastrophic. Mitigating the consequences of such phenomena directly depends on the reliability and efficiency of information about the state of parameters of many technological processes, mine workings and facilities located in them. At failure of standard systems of industrial telemetry in conditions of underground mining the creation of new information channels and places of information measurementbecomes practically impossible in case of emergency situation development. This predetermines necessity of use of essentially new systems of gathering and transfer of the information, based on robotized autonomous complexes. The task of acquiring reliable information about the situation in an emergency mine working with the help of drones (unmanned aerial vehicles or UAV) in order to make rational decisions in the course of the rescue operation is quite relevant. The aim of the paper was to develop a system of automatic control of an unmanned aerial vehicle (UAV) movement in confined space of a mine working, with significant perturbations of the mine air flow. The mathematical model of UAV movement in mine conditions, based on Euler angles or quaternions, was substantiated. The method of positioning through triangulation with the use of radio beacons was accepted as the basic method that allowed to determine the current position of an UAV. It was proposed to solve the problem of creation of the automatic system for an unmanned aerial vehicle movement control with the use of a hierarchical multiloop control system. The route planning algorithm was formed on the basis of the Dijkstra algorithm. For this purpose, discretization of the future motion space was performed, a labeled connected graph was constructed, on which the arc weights were the distances between the route points. A simulation experiment was implemented. The average deviation from the planned trajectory when flying at a speed of 10 m/s with payload mass up to 0.6 kg did not exceed 1 m, and the maximum deviation was unacceptably large. When flying at 6 m/s with payload mass up to 0.6 kg the average deviation did not exceed 0.3 m, and the maximum deviation, 1.2 m. The results of simulation of movement along the route towards the disturbing mine airflow showed that the control system allowed the UAV with payload of 0.6 kg to withstand the oncoming flow up to 8 m/s. It was obtained that with payload mass of 0.6 kg, the braking distance does not exceed 6 m if the UAV had a speed of 6 m/s, and the braking distance does not exceed 12 m at the speed of 10 m/s. The performed simulation studies confirmed the operating capability of the developed system for automatic motion control.

Abstract In this work, the mutual arrangement of polyelectrolytes of multilayer polyelectrolyte microcapsules (with layers—[PAH/PSS]3PAH) by determination of the dissociation level of polyallylamine (PAH) from the surface of a polyelectrolyte microcapsules (PMC) of various types was studied: PMC with a dissolved CaCO3 core after preparation, PMC with an undissolved CaCO3 core and PMC with an encapsulated protein. It was concluded that the polyelectrolyte layers are mixed in the entire shell of the capsules with a dissolved CaCO3 core. In the case of the PMC with an undissolved CaCO3 core, such mixing of polyelectrolyte layers does not occur. That fact allows us to conclude that the mixing of polyelectrolytes layers mixing at the stage of dissolution of CaCO3 core. The PMC with encapsulated protein has partial mixing of polyelectrolytes layers. That phenomenon may be due to the fact that seven-layered protein-containing microcapsules already have a dense and well-formed shell. The obtained data correlate with the data on the study of the surface charge of microcapsules.

Abstract The Cookiecutter shark (Isistius brasiliensis) is an ectoparasitic, mesopelagic shark that is known for removing plugs of tissue from larger prey, including teleosts, chondrichthyans, cephalopods, and marine mammals. Although this species is widely distributed throughout the world’s tropical and subtropical oceanic waters, like many deep-water species, it remains very poorly understood due to its mesopelagic distribution. We used a suite of biochemical tracers, including stable isotope analysis (SIA), fatty acid analysis (FAA), and environmental DNA (eDNA), to investigate the trophic ecology of this species in the Central Pacific around Hawaii. We found that large epipelagic prey constituted a relatively minor part of the overall diet. Surprisingly, small micronektonic and forage species (meso- and epipelagic) are the most important prey group for Cookiecutter sharks across the studied size range (17–43 cm total length), with larger mesopelagic species or species that exhibit diel vertical migration also being important prey. These results were consistent across all the tracer techniques employed. Our results indicate that Cookiecutter sharks play a unique role in pelagic food webs, feeding on prey ranging from the largest apex predators to small, low trophic level species, in particular those that overlap with the depth distribution of the sharks throughout the diel cycle. We also found evidence of a potential shift in diet and/or habitat with size and season. Environmental DNA metabarcoding revealed new prey items for Cookiecutter sharks while also demonstrating that eDNA can be used to identify recent prey in stomachs frozen for extended periods. Integrating across chemical tracers is a powerful tool for investigating the ecology of elusive and difficult to study species, such as meso- and bathypelagic chondrichthyans, and can increase the amount of information gained from small sample sizes. Better resolving the foraging ecology of these mesopelagic predators is critical for effective conservation and management of these taxa and ecosystems, which are intrinsically vulnerable to overfishing and exploitation.

Background: Recently, monoclonal-antibody–conjugated immunomagnetic separation (IMS) procedure combined with quantitative reverse transcription-polymerase chain reaction (qRT-PCR) has been used for quantifying non-cultivated human noroviruses (HuNoVs). Methods: We examined the efficacy of 27 commercially available disinfectants and a prototype against GII.4 strain HuNoV through the IMS/qRT-PCR assay. Results: The average log reduction in viral titer in vitro varied among the disinfectants. The prototype was the most effective with an average log reduction of 6.86 log. Conclusions: The IMS/RT-qPCR assay is an effective method to evaluate the activities of disinfectants against GII.4 HuNoV in vitro. Further work is needed to enhance the virucidal activity of the prototype disinfectant against more resistant HuNoV strains.

Context: Multiparametric magnetic resonance imaging (mpMRI) detects most, but not all, clinically significant prostate cancer. The genetic basis of prostate cancer visibility and invisibility on mpMRI remains uncertain. Objective: To systematically review the literature on differential gene expression between mpMRI-visible and mpMRI-invisible prostate cancer, and to use bioinformatic analysis to identify enriched processes or cellular components in genes validated in more than one study. Evidence acquisition: We performed a systematic literature search of the Medline, EMBASE, PubMed, and Cochrane databases up to January 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The primary endpoint was differential genetic features between mpMRI-visible and mpMRI-invisible tumours. Secondary endpoints were explanatory links between gene function and mpMRI conspicuity, and the prognostic value of differential gene enrichment. Evidence synthesis: We retrieved 445 articles, of which 32 met the criteria for inclusion. Thematic synthesis from the included studies showed that mpMRI-visible cancer tended towards enrichment of molecular features associated with increased disease aggressivity, including phosphatase and tensin homologue (PTEN) loss and higher genomic classifier scores, such as Oncotype and Decipher. Three of the included studies had accompanying publicly available data suitable for further bioinformatic analysis. An over-representation analysis of these datasets revealed increased expression of genes associated with extracellular matrix components in mpMRI-visible tumours. Conclusions: Prostate cancer that is visible on mpMRI is generally enriched with molecular features of tumour development and aggressivity, including activation of proliferative signalling, DNA damage, and inflammatory processes. Additionally, there appears to be concordant cellular components and biological processes associated with mpMRI conspicuity, as highlighted by bioinformatic analysis of large genetic datasets. Patient summary: Prostate cancer that is detected by magnetic resonance imaging (MRI) tends to have genetic features that are associated with more aggressive disease. This suggests that MRI can be used to assess the likelihood of aggressive prostate cancer, based on tumour visibility.

Diamond dust particles were identified within patients’ eyes both during vitrectomy procedures using diamond-dusted membrane scrapers and in postoperative clinical examinations. The particles had no impact on the patients’ vision and caused no apparent sequelae. Scanning electron microscopy analysis showed the average particle size to be 23.4 μm and an unequal surface area for particle adhesion onto the soft tip. It was determined that diamond dust particles can dislodge from the silicone tip of the Tano diamond-dusted membrane scrapers during the insertion into valve trocars throughout vitrectomy operations and deposit on the retinal surface or within macular holes. Ophthalmologists should be aware of residual diamond particles during procedures and consider diamond dust retinopathy in the differential diagnosis of crystalline retinopathies. Understanding the appearance of residual particles on the retina allows for future studies revealing the long-term impact on patient’s visual performance.

Counterfeit medicines are a threat to patient health and public safety. Here, the authors use random patterns formed by fluorescent silk microparticles with various excitation and emission pairs as an edible physical unclonable function that can directly be attached onto the surface of medicines.

Background: Designing questionnaires is a key point of epidemiological studies assessing human exposure to chemicals. The lack of validated questionnaires can lead to the use of previously developed and sub-optimally adapted questionnaires, which may result in information biases that affect the study’s validity. On this ground, a multidisciplinary group of researchers developed a series of tools to support data collection within the HBM4EU initiative. The objective of this paper is to share the process of developing HBM4EU questionnaires, as well as to provide researchers with harmonized procedures that could help them to design future questionnaires to assess environmental exposures. Methods: In the frame of the work package on survey design and fieldwork of the HBM4EU, researchers carried out procedures necessary for the development of quality questionnaires and related data collection tools. These procedures consisted of a systematic search to identify questionnaires used in previous human biomonitoring (HBM) studies, as well as the development of a checklist and evaluation sheet to assess the questionnaires identified. The results of these evaluations were taken into consideration for the development of the final questionnaires. Results: The main points covered by each of the sections included in HBM4EU questionnaires are described and discussed in detail. Additional tools developed for data collection in the HBM4EU (e.g. non-responder questionnaire, satisfaction questionnaire, matrix-specific questionnaire) are also addressed. Special attention is paid to the limitations faced and hurdles overcome during the process of questionnaire development. Conclusions: Designing questionnaires for use in HBM studies requires substantial effort by a multidisciplinary team to guarantee that the quality of the information collected meets the study’s objectives. The process of questionnaire development described herein will contribute to improve the harmonization of HBM studies within the social and environmental context of the EU countries.

Summary: The complex 16p11.2 deletion syndrome (16pdel) is accompanied by neurological disorders, including epilepsy, autism spectrum disorder, and intellectual disability. We demonstrated that 16pdel iPSC differentiated neurons from affected people show augmented local field potential activity and altered ceramide-related lipid species relative to unaffected. FAM57B, a poorly characterized gene in the 16p11.2 interval, has emerged as a candidate tied to symptomatology. We found that FAM57B modulates ceramide synthase (CerS) activity, but is not a CerS per se. In FAM57B mutant human neuronal cells and zebrafish brain, composition and levels of sphingolipids and glycerolipids associated with cellular membranes are disrupted. Consistently, we observed aberrant plasma membrane architecture and synaptic protein mislocalization, which were accompanied by depressed brain and behavioral activity. Together, these results suggest that haploinsufficiency of FAM57B contributes to changes in neuronal activity and function in 16pdel syndrome through a crucial role for the gene in lipid metabolism.

What are the most efficient and effective methods in measuring outcomes for assurance of learning in higher education? This study examines the merits of outsourcing part of the assessment workload by comparing ratings completed by trained student interns to ratings completed by faculty. Faculty evaluation of students' written work samples provides the most detailed, actionable data useful for improving the curriculum. While this approach may be efficacious, it is also labor-intensive. Both the faculty and student interns were trained to use a scoring rubric developed for this assessment to rate undergraduate student essay responses to an ethical reasoning scenario. The convergent validity, discriminant validity, and source bias showed no significant difference between the values for the student raters versus those for the faculty raters. These findings support the hypothesis that trained student interns can do as well as faculty at evaluating undergraduate student work samples.

Ataxia Telangiectasia (A-T) and Ataxia with Ocular Apraxia Type 1 (AOA1) are devastating neurological disorders caused by null mutations in the genome stability genes, A-T mutated (ATM) and Aprataxin (APTX), respectively. Our mechanistic understanding and therapeutic repertoire for treating these disorders are severely lacking, in large part due to the failure of prior animal models with similar null mutations to recapitulate the characteristic loss of motor coordination (i.e., ataxia) and associated cerebellar defects. By increasing genotoxic stress through the insertion of null mutations in both the Atm (nonsense) and Aptx (knockout) genes in the same animal, we have generated a novel mouse model that for the first time develops a progressively severe ataxic phenotype associated with atrophy of the cerebellar molecular layer. We find biophysical properties of cerebellar Purkinje neurons (PNs) are significantly perturbed (e.g., reduced membrane capacitance, lower action potential [AP] thresholds, etc.), while properties of synaptic inputs remain largely unchanged. These perturbations significantly alter PN neural activity, including a progressive reduction in spontaneous AP firing frequency that correlates with both cerebellar atrophy and ataxia over the animal’s first year of life. Double mutant mice also exhibit a high predisposition to developing cancer (thymomas) and immune abnormalities (impaired early thymocyte development and T-cell maturation), symptoms characteristic of A-T. Finally, by inserting a clinically relevant nonsense-type null mutation in Atm, we demonstrate that Small Molecule Read-Through (SMRT) compounds can restore ATM production, indicating their potential as a future A-T therapeutic.

Abstract The advanced molybdenum-based rare process experiment (AMoRE) aims to search for neutrinoless double beta decay ($$0\nu \beta \beta $$ 0νββ ) of $$^{100}$$ 100 Mo with $$\sim 100\,\hbox {kg}$$ ∼100kg of $$^{100}$$ 100 Mo-enriched molybdenum embedded in cryogenic detectors with a dual heat and light readout. At the current, pilot stage of the AMoRE project we employ six calcium molybdate crystals with a total mass of 1.9 kg, produced from $$^{48}$$ 48 Ca-depleted calcium and $$^{100}$$ 100 Mo-enriched molybdenum ($$^{48{{\text {depl}}}}\hbox {Ca}^{100}\hbox {MoO}_{4}$$ 48deplCa100MoO4 ). The simultaneous detection of heat (phonon) and scintillation (photon) signals is realized with high resolution metallic magnetic calorimeter sensors that operate at milli-Kelvin temperatures. This stage of the project is carried out in the Yangyang underground laboratory at a depth of 700 m. We report first results from the AMoRE-Pilot $$0\nu \beta \beta $$ 0νββ search with a 111 kg day live exposure of $$^{48{{\text {depl}}}}\hbox {Ca}^{100}\hbox {MoO}_{4}$$ 48deplCa100MoO4 crystals. No evidence for $$0\nu \beta \beta $$ 0νββ decay of $$^{100}$$ 100 Mo is found, and a upper limit is set for the half-life of $$0\nu \beta \beta $$ 0νββ of $$^{100}$$ 100 Mo of $$T^{0\nu }_{1/2} > 9.5\times 10^{22}~\hbox {years}$$ T1/20ν>9.5×1022years at 90% C.L. This limit corresponds to an effective Majorana neutrino mass limit in the range $$\langle m_{\beta \beta }\rangle \le (1.2-2.1)\,\hbox {eV}$$ ⟨mββ⟩≤(1.2-2.1)eV .

Current treatments for chronic pain have limited benefit. We describe a resilience intervention for individuals with chronic pain which is based on a model of viewing chronic pain as dysregulated homeostasis and which seeks to restore homeostatic self-regulation using strategies exemplified by survivors of extreme environments. The intervention is expected to have broad effects on well-being and positive emotional health, to improve cognitive functions, and to reduce pain symptoms thus helping to transform the suffering of pain into self-growth. A total of 88 Veterans completed the pre-assessment and were randomly assigned to either the treatment intervention (n = 38) or control (n = 37). Fifty-eight Veterans completed pre- and post-testing (intervention n = 31, control = 27). The intervention covered resilience strengths organized into four modules: (1) engagement, (2) social relatedness, (3) transformation of pain and (4) building a good life. A broad set of standardized, well validated measures were used to assess three domains of functioning: health and well-being, symptoms, and cognitive functions. Two-way Analysis of Variance was used to detect group and time differences. Broadly, results indicated significant intervention and time effects across multiple domains: (1) Pain decreased in present severity [F(1, 56) = 5.02, p < 0.05, η2p = 0.08], total pain over six domains [F(1, 56) = 14.52, p < 0.01, η2p = 0.21], and pain interference [F(1, 56) = 6.82, p < 0.05, η2p = 0.11]; (2) Affect improved in pain-related negative affect [F(1, 56) = 7.44, p < 0.01, η2p = 0.12], fear [F(1, 56) = 7.70, p < 0.01, η2p = 0.12], and distress [F(1, 56) = 10.87, p < 0.01, η2p = 0.16]; (3) Well-being increased in pain mobility [F(1, 56) = 5.45, p < 0.05, η2p = 0.09], vitality [F(1, 56) = 4.54, p < 0.05, η2p = 0.07], and emotional well-being [F(1, 56) = 5.53, p < 0.05, η2p = 0.09] Mental health symptoms and the cognitive functioning domain did not reveal significant effects. This resilience intervention based on homeostatic self-regulation and survival strategies of survivors of extreme external environments may provide additional sociopsychobiological tools for treating individuals with chronic pain that may extend beyond treating pain symptoms to improving emotional well-being and self-growth.Clinical Trial Registration: Registered with ClinicalTrials.gov (NCT04693728).

In animal studies, prolonged sedation with general anesthetics has resulted in cognitive impairments that can last for days to weeks after exposure. One mechanism by which anesthesia may impair cognition is by decreasing adult hippocampal neurogenesis. Several studies have seen a reduction in cell survival after anesthesia in rodents with most studies focusing on two particularly vulnerable age windows: the neonatal period and old age. However, the extent to which sedation affects neurogenesis in young adults remains unclear. Adult neurogenesis in the dentate gyrus (DG) was analyzed in male and female rats 24 h after a 4-h period of sedation with isoflurane, propofol, midazolam, or dexmedetomidine. Three different cell populations were quantified: cells that were 1 week or 1 month old, labeled with the permanent birthdate markers EdU or BrdU, respectively, and precursor cells, identified by their expression of the endogenous dividing cell marker proliferating cell nuclear antigen (PCNA) at the time of sacrifice. Midazolam and dexmedetomidine reduced cell proliferation in the adult DG in both sexes but had no effect on postmitotic cells. Propofol reduced the number of relatively mature, 28-day old, neurons specifically in female rats and had no effects on younger cells. Isoflurane had no detectable effects on any of the cell populations examined. These findings show no general effect of sedation on adult-born neurons but demonstrate that certain sedatives do have drug-specific and sex-specific effects. The impacts observed on different cell populations predict that any cognitive effects of these sedatives would likely occur at different times, with propofol producing a rapid but short-lived impairment and midazolam and dexmedetomidine altering cognition after a several week delay. Taken together, these studies lend support to the hypothesis that decreased neurogenesis in the young adult DG may mediate the effects of sedation on cognitive function.

Backgrounds. In cases of scaphoid fractures and the absence of adequate surgical treatment over time, the wound surfaces of its fragments are lysed, the scaphoid and its subluxation to the palmar side are deformed. The treatment of this pathology presents significant difficulties due to the impossibility of an adequate restoration of the original form of the scaphoid. Materials and methods. A method of surgical treatment of SNAC/SLAC wrist with scaphoid excision and creation of capitolunate arthrodesis was developed. Saved the place of attachment to the base of the second metacarpal bone, cutting off the tendon of the wrist long radial extensor in the tendon-muscle part at the level of upper trird of the lower arm is making. The tendon is rolling up, suturing and tightly putting into removed scaphoid bed. As a result the rolled tendon of the wrist long radial extensor putted into removed scaphoid bed works as an elastic damper that do not allow the trapezoid and the trapezium to migrate. Results. Saving the tendon attachment place to the base of the second metacarpal bone keeps it's blood supply that impedes it's degeneration and lysis. Conclusions. The proposed method is technically simple, does not require sophisticated equipment and can be used for surgical treatment of SNAC and SLAC syndromes of the carpal joint.

Limitation in cell sources for autologous cell therapy has been a recent focus in stem cell therapy and tissue engineering. Among various research advances, direct conversion, or transdifferentiation, is a notable and feasible strategy for the generation and acquirement of wanted cell source. So far, utilizing cell transdifferentiation technology in tissue engineering was mainly restricted at achieving single wanted cell type from diverse cell types with high efficiency. However, regeneration of a complete tissue always requires multiple cell types which poses an intrinsic complexity. In this study, enhanced osteogenic differentiation was achieved by transient ectopic expression of octamer-binding transcription factor 4 ( OCT-4 ) gene followed by bone morphogenetic protein 4 treatment on human umbilical vein endothelial cells. OCT-4 transfection and bone morphogenetic protein 4 treatment resulted in enhanced expression of osteogenic markers such as core-binding factor alpha 1, alkaline phosphatase, and collagen 1 compared with bone morphogenetic protein 4 treatment alone. Furthermore, we employed gelatin-heparin cryogel in cranial defect model for in vivo bone formation. Micro-computed tomography and histological analysis of in vivo samples showed that OCT-4 transfection followed by bone morphogenetic protein 4 treatment resulted in efficient transdifferentiation of endothelial cells to osteogenic cells. These results suggest that the combination of OCT-4 and bone morphogenetic protein 4 on endothelial cells would be a reliable multicellular transdifferentiation model which could be applied for bone tissue engineering.

Abstract Beyond structural and chemical barriers to pathogens, the immune system has two fundamental lines of defense: innate immunity and adaptive immunity. Innate immunity is the first immunological mechanism for fighting against an intruding pathogen. It is a rapid immune response, initiated within minutes or hours after aggression, that has no immunologic memory. Adaptive immunity, on the other hand, is antigen-dependent and antigen-specific; it has the capacity for memory, which enables the host to mount a more rapid and efficient immune response upon subsequent exposure to the antigen. There is a great deal of synergy between the adaptive immune system and its innate counterpart, and defects in either system can provoke illness or disease, such as inappropriate inflammation, autoimmune diseases, immunodeficiency disorders and hypersensitivity reactions. This article provides a practical overview of innate and adaptive immunity, and describes how these host defense mechanisms are involved in both heath and illness.

Abstract Background In Norway, data on the association between second-hand tobacco smoke (SHS) exposure at home and respiratory symptoms in adults are limited. Methods We assessed the association between self-reported exposure to SHS and the prevalence of respiratory symptoms among never-smokers aged 16 to 50 years from the general population who were included in a cross-sectional population-based study in Telemark County, Norway. Logistic regression analysis was used to estimate the odds ratios of symptoms among 8850 never-smokers who provided an affirmative response to questions regarding SHS; 504 (5.7%) of these reported that they lived in a home with daily or occasional indoor smoking. Results Productive cough and nocturnal dyspnoea were statistically associated with daily SHS exposure (ORs 1.5 [95% CI 1.04–2.0] and 1.8 [1.2–2.7], respectively). In analyses stratified by gender, nocturnal dyspnoea was associated with SHS among women (OR 1.8 [1.1–3.1]), but not among men (OR 0.93 [0.49–1.8]). Symptoms were not associated with occasional SHS exposure in the entire group, but infrequent exposure among men only was associated with increased prevalence of chronic cough; (OR 1.6; [1.04–2.6]) and was negatively associated with wheeze; (OR 0.44 [0.21–0.92)]. Conclusions Daily SHS exposure in private homes was associated with productive cough and nocturnal dyspnoea. Our results suggest that preventive measures may be needed to reduce the respiratory effects of SHS at home. Trial registration ClinicalTrials.gov Identifier: NCT02073708 Registered February 27. 2014.

Abstract The recent advances in photocatalysis have opened a variety of new possibilities for energy and biomedical applications. In particular, plasmonic photocatalysis using hybridization of semiconductor materials and metal nanoparticles has recently facilitated the rapid progress in enhancing photocatalytic efficiency under visible or solar light. One critical underlying aspect of photocatalysis is that it generates and releases reactive oxygen species (ROS) as intermediate or final products upon light excitation or activation. Although plasmonic photocatalysis overcomes the limitation of UV irradiation, synthesized metal/semiconductor nanomaterial photocatalysts often bring up biohazardous and environmental issues. In this respect, this review article is centered in identifying natural photosensitizing organic materials that can generate similar types of ROS as those of plasmonic photocatalysis. In particular, we propose the idea of plasmonic photocatalyst-like fluorescent proteins for ROS generation under visible light irradiation. We recapitulate fluorescent proteins that have Type I and Type II photosensitization properties in a comparable manner to plasmonic photocatalysis. Plasmonic photocatalysis and protein photosensitization have not yet been compared systemically in terms of ROS photogeneration under visible light, although the phototoxicity and cytotoxicity of some fluorescent proteins are well recognized. A comprehensive understanding of plasmonic photocatalyst-like fluorescent proteins and their potential advantages will lead us to explore new environmental, biomedical, and defense applications.

Light in biological media is known as freely diffusing because interference is negligible. Here, the authors demonstrate Anderson localization of light from quasi-two-dimensional nanostructures in silk fibres.

Effective communication is fundamental to the quality and safety of healthcare. In the U.S., language and cultural differences combined with low health literacy are challenges that physicians must overcome. The Spanish-speaking patient population continues to grow and is disproportionately affected by this, with 25% speaking little to no English. In our hand and upper extremity surgery practice, a common problem arises both with verbal Spanish communication and with the physical exam. The hand and upper extremity examination requires a high level of patient involvement to elucidate subtle derangements in individual tendon or nerve function. Our purpose is to summarize a model upper extremity clinical encounter in Spanish and provide a guide for patient-physician interaction, particularly during the physical exam where visual aids can be more useful than simple verbal commands. This guide is a simple step towards enhanced communication and understanding between providers and patients, with the goal of providing higher quality care with greater efficiency and satisfaction. The purpose is not to replace the professional interpreter, but to augment the physician-patient interaction during the upper extremity clinical encounter. Incorporating a cross-language template may yield improved patient understanding, enhanced participation in the examination leading to better diagnosis, and improved satisfaction for both patient and provider. Key words: Communication, Language, Patient satisfaction, Spanish, Upper extremity

Aldehyde dehydrogenase 1 isoforms A1 and A3 have been implicated as functional biomarkers associated with distinct molecular subtypes of glioblastoma and glioblastoma stem cells. However, the exact roles of these isoforms in different types of glioma cells remain unclear. The purpose of this study was to dissect the association of A1 or A3 isoforms with stem and non-stem glioblastoma cells. This study has undertaken a systematic characterization of A1 and A3 proteins in glioblastoma tissues and a panel of glioblastoma stem cells using immunocytochemical and immunofluorescence staining, Western blot and the subcellular fractionation methodology. Our main findings are (i) human GSCs express uniformly ALDH1A3 but not the ALDH1A1 isoform whereas non-stem glioma cells comparably express both isoforms; (ii) there is an abundance of ALDH1A3 peptides that prevail over the full-length form in glioblastoma stem cells but not in non-stem glioma cells; (iii) full-length ALDH1A3 and ALDH1A3 peptides are spatially segregated within the cell; and (vi) the abundance of full-length ALDH1A3 and ALDH1A3 peptides is sensitive to MG132-mediated proteasomal inhibition. Our study further supports the association of ALDH1A3 with glioblastoma stem cells and provide evidence for the regulation of ALDH1A3 activities at the level of protein turnover.

We report on a tunable solid-state approach to modify the acidity of cotton substrates using citric, oxalic, and fumaric acids. The first stage of the method involves soaking the cotton swatches in an ethanolic saturated solution of the corresponding acid. After drying, the carboxylation reaction proceeds at high temperature (T > 100 °C) and in solid state. We quantified the effect of temperature and reaction time on the solid-state carboxylation reaction, which allowed us to tune the carboxylation degree and the acidity of the surface. We characterized the modified cotton by performing adsorption isotherms and by determining the kinetics of adsorption of a cationic dye: methylene blue (MB). We found that the MB uptake kinetics varied as a function of the acidic strength of the surface, which is closely related to the strength of the acid used for surface modification. The proposed solid-state cotton carboxylation procedure allows us to achieve sustainable cotton modification, which constitutes a starting point for several applications using cotton as the substrate.

The capacity of terrestrial ecosystems to sequester carbon dioxide (CO2) from the atmosphere is expected to be altered by climate change and CO2 fertilization, but this projection is limited by our understanding of how the soil system interacts with plants. Understanding the soil–vegetation interactions is essential to assess the magnitude and response of terrestrial ecosystems to the changing climate. Here, we used soil profile and satellite data to explore the role that soil properties play in regulating water and carbon use by plants. Data obtained for 19 terrestrial ecosystem sites in a warm temperate and humid climate were used to investigate the relationship between remotely sensed data and soil physical and chemical properties. Classification and regression tree results showed that in situ soil carbon isotope (δ13C), and soil order were significant predictors (r2 = 0.39, mean absolute error (MAE) = 0 of 0.175 gC/KgH2O) of remotely sensed water use efficiency (WUE) based on the Moderate Resolution Imaging Spectroradiometer (MODIS). Soil extractable calcium (Ca), and land cover type were significant predictors of remotely sensed carbon use efficiency (CUE) based on MODIS and Landsat data-(r2 = 0.64–0.78, MAE = 0.04–0.06). We used gross primary productivity (GPP) derived from solar-induced fluorescence (SIF) data, based on the Orbiting Carbon Observatory-2 (OCO-2), to calculate WUE and CUE (referred to as WUESIF and CUESIF, respectively) for our study sites. The regression tree analysis revealed that soil organic matter and soil extractable magnesium (Mg), δ13C, and soil silt content were the important predictors of both WUESIF (r2 = 0.19, MAE = 0.64 gC/KgH2O) and CUESIF (r2 = 0.45, MAE = 0.1), respectively. Our results revealed the importance of soil extractable Ca, soil carbon (S13C is a facet of soil carbon content), and soil organic matter predicting CUE and WUE. Insights gained from this study highlighted the importance of biotic and abiotic factors regulating plant and soil interactions. These types of data are timely and critical for accurate predictions of how terrestrial ecosystems respond to climate change.

Abstract Clear cell renal cell carcinoma (ccRCC) has been previously classified into putative discrete prognostic subtypes by gene expression profiling. To investigate the robustness of these proposed subtype classifications, we evaluated 12 public datasets, together with a new dataset of 265 ccRCC gene expression profiles. Consensus clustering showed unstable subtype and principal component analysis (PCA) showed a continuous spectrum both within and between datasets. Considering the lack of discrete delineation and continuous spectrum observed, we developed a continuous quantitative prognosis score (Continuous Linear Enhanced Assessment of RCC, or CLEAR score). Prognostic performance was evaluated in independent cohorts from The Cancer Genome Atlas (TCGA) (n = 414) and EMBL-EBI (n = 53), CLEAR score demonstrated both superior prognostic estimates and inverse correlation with anti-angiogenic tyrosine-kinase inhibition in comparison to previously proposed discrete subtyping classifications. Inverse correlation with high-dose interleukin-2 outcomes was also observed for the CLEAR score. Multiple somatic mutations (VHL, PBRM1, SETD2, KDM5C, TP53, BAP1, PTEN, MTOR) were associated with the CLEAR score. Application of the CLEAR score to independent expression profiling of intratumoral ccRCC regions demonstrated that average intertumoral heterogeneity exceeded intratumoral expression heterogeneity. Wider investigation of cancer biology using continuous approaches may yield insights into tumor heterogeneity; single cell analysis may provide a key foundation for this approach.

Abstract Structural arrangement and dimension play vital roles in wave transport and amplification as they can restrict the volume explored by the waves. However, it is challenging to systematically investigate the interplay among structural, optical, and mechanical properties, in part because of limited experimental platforms that modulate the structural arrangement in a continuous manner. We present light amplification action in Rhodamine B doped silk fibroin (SF) nanofibrous scaffolds and its modulation via the control of the alignment or directionality of SF nanofibers through an electrospinning procedure. Random lasing features of such scaffolds are examined as a function of structural arrangement of the SF nanofibers, and optical-structural-mechanical relationships of the SF-based structures are examined. As SF nanofibers are aligned parallel undergoing a transition from three to quasi-two dimension, light amplification features (e.g., lasing threshold and output power) enhanced, which also strongly correlated with mechanical characteristics (i.e., Young’s moduli) of the scaffolds. We confirm such optical characteristics using quasi-mode analyses based on the finite element method. We further demonstrate non-contact, in situ measurement of alternations in lasing features of the scaffolds while the specimens are under tensile loads. These results may highlight potential utility of the scaffolds as a flexible and biocompatible sensor.

Asthma often remains uncontrolled, despite the fact that the pharmacological treatment has undergone large changes. We studied changes in the treatment of asthma over a 20-year period and identified factors associated with the regular use of inhaled corticosteroid (ICS) treatment. Changes in the use of medication were determined in 4617 randomly selected subjects, while changes in adults with persistent asthma were analysed in 369 participants. The study compares data from three surveys in 24 centres in 11 countries. The use of ICSs increased from 1.7% to 5.9% in the general population and the regular use of ICSs increased from 19% to 34% among persistent asthmatic subjects. The proportion of asthmatic subjects reporting asthma attacks in the last 12 months decreased, while the proportion that had seen a doctor in the last 12 months remained unchanged (42%). Subjects with asthma who had experienced attacks or had seen a doctor were more likely to use ICSs on a regular basis. Although ICS use has increased, only one-third of subjects with persistent asthma take ICSs on a regular basis. Less than half had seen a doctor during the last year. This indicates that underuse of ICSs and lack of regular healthcare contacts remains a problem in the management of asthma.

The association between exacerbation aetiology and exacerbation frequency is poorly understood. We analysed 2-year follow-up data from a prospective observational study of patients with chronic obstructive pulmonary disease (COPD) (www.clinicaltrials.gov identifier number NCT01360398) to evaluate year-to-year variation in exacerbation frequency and related aetiology. A total of 127 patients underwent blood and sputum sampling monthly and at exacerbation to detect respiratory infections and eosinophilic inflammation; 103 continued into year 2 and 88 completed both years. The most common bacterial species at stable state and exacerbation was Haemophilus influenzae. Among infrequent exacerbators (one exacerbation per year), the incidence of viral infection at exacerbation was high (60.0% (95% CI 35.1–81.7%) in year 1 and 78.6% (53.4–94.2%) in year 2). Those with more frequent exacerbations tended to have higher relative incidence of bacterial than viral infection. Patients with at least two additional exacerbations in year 2 versus year 1 had a higher risk of H. influenzae colonisation at stable state than those with at least two fewer exacerbations, as detected by culture (OR 1.43 (95% CI 0.71–2.91) versus 0.63 (0.40–1.01), p=0.06) and PCR (1.76 (95% CI 0.88–3.51) versus 0.56 (0.37–0.86), p

BACKGROUND:Epidemiological data suggests that obstructive sleep apnea (OSA) is associated with increased cancer incidence and mortality. We investigate the effects of cyclical intermittent hypoxia (CIH), akin to the underlying pathophysiology of OSA, on lung cancer progression and metastatic profile in a mouse model. METHODS:Intrathoracic injection of Ad5CMVCre virus into a genetically engineered mouse (GEM) KrasG12D+/-; p53fl/fl; myristolated-p110αfl/fl-ROSA-gfp was utilized to induce a solitary lung cancer. Male mice were then exposed to either CIH or Sham for 40-41 days until harvest. To monitor malignant progression, serial micro CT scans with respiratory gating (no contrast) was performed. To detect spontaneous metastases in distant organs, H&E and immunohistochemistry were performed. RESULTS:Eighty-eight percent of injected Ad5CMVCre virus was recovered from left lung tissue, indicating reliable and accurate injections. Serial micro CT demonstrated that CIH increases primary lung tumor volume progression compared to Sham on days 33 (p = 0.004) and 40 (p

During periods in which glucose absorption from the gastrointestinal (GI) tract is insufficient to meet body requirements, hepatic gluconeogenesis plays a key role to maintain normal blood glucose levels. The current studies investigated the role in this process played by vasodilatory-associated phosphoprotein (VASP), a protein that is phosphorylated in hepatocytes by cAMP/protein kinase A (PKA), a key mediator of the action of glucagon. We report that following stimulation of hepatocytes with 8Br-cAMP, phosphorylation of VASP preceded induction of genes encoding key gluconeogenic enzymes, glucose-6-phosphatase (G6p) and phosphoenolpyruvate carboxykinase (Pck1), and that VASP overexpression enhanced this gene induction. Conversely, hepatocytes from mice lacking VASP (Vasp-/-) displayed blunted induction of gluconeogenic enzymes in response to cAMP, and Vasp-/- mice exhibited both greater fasting hypoglycemia and blunted hepatic gluconeogenic enzyme gene expression in response to fasting in vivo. These effects of VASP deficiency were associated with reduced phosphorylation of both CREB (a key transcription factor for gluconeogenesis that lies downstream of PKA) and histone deacetylase 4 (HDAC4), a combination of effects that inhibit transcription of gluconeogenic genes. These data support a model in which VASP functions as a molecular bridge linking the two key signal transduction pathways governing hepatic gluconeogenic gene expression.