Factors influencing mercury exposure in Arctic-breeding shorebirds.

Mercury (Hg) pollution remains a concern to Arctic ecosystems, due to long-range transport from southern industrial regions and melting permafrost and glaciers. The objective of this study was to identify intrinsic, extrinsic, and temporal factors influencing Hg concentrations in Arctic-breeding shorebirds and highlight regions and species at greatest risk of Hg exposure. We analyzed 1094 blood and 1384 feather samples from 12 shorebird species breeding at nine sites across the North American Arctic during 2012 and 2013. Blood Hg concentrations, which reflect Hg exposure in the local area in individual shorebirds: 1) ranged from 0.01-3.52 µg/g ww, with an overall mean of 0.30 ± 0.27 µg/g ww; 2) were influenced by species and study site, but not sampling year, with birds sampled near Utqiagvik, AK, having the highest concentrations; and 3) were influenced by foraging habitat at some sites. Feather Hg concentrations, which reflected Hg exposure from the wintering grounds: 1) ranged from 0.07-12.14 µg/g fw in individuals, with an overall mean of 1.14 ± 1.18 µg/g fw; and 2) were influenced by species and year. Most Arctic-breeding shorebirds had blood and feather Hg concentrations at levels where no adverse effects of exposure were predicted, though some individuals sampled near Utqiagvik had Hg levels that would be considered of concern. Overall, these data increase our understanding of how Hg is distributed in the various shorebird breeding areas of the Arctic, what factors predispose Arctic-breeding shorebirds to Hg exposure, and lay the foundation for future monitoring efforts.

Mercury in Neotropical birds: a synthesis and prospectus on 13 years of exposure data.

Environmental mercury (Hg) contamination of the global tropics outpaces our understanding of its consequences for biodiversity. Knowledge gaps of pollution exposure could obscure conservation threats in the Neotropics: a region that supports over half of the world's species, but faces ongoing land-use change and Hg emission via artisanal and small-scale gold mining (ASGM). Due to their global distribution and sensitivity to pollution, birds provide a valuable opportunity as bioindicators to assess how accelerating Hg emissions impact an ecosystem's ability to support biodiversity, and ultimately, global health. We present the largest database on Neotropical bird Hg concentrations (n = 2316) and establish exposure baselines for 322 bird species spanning nine countries across Central America, South America, and the West Indies. Patterns of avian Hg exposure in the Neotropics broadly align with those in temperate regions: consistent bioaccumulation across functional groups and high spatiotemporal variation. Bird species occupying higher trophic positions and aquatic habitats exhibited elevated Hg concentrations that have been previously associated with reductions in reproductive success. Notably, bird Hg concentrations were over four times higher at sites impacted by ASGM activities and differed by season for certain trophic niches. We developed this synthesis via a collaborative research network, the Tropical Research for Avian Conservation and Ecotoxicology (TRACE) Initiative, which exemplifies inclusive, equitable, and international data-sharing. While our findings signal an urgent need to assess sampling biases, mechanisms, and consequences of Hg exposure to tropical avian communities, the TRACE Initiative provides a meaningful framework to achieve such goals. Ultimately, our collective efforts support and inform local, scientific, and government entities, including Parties of the United Nations Minamata Convention on Mercury, as we continue working together to understand how Hg pollution impacts biodiversity conservation, ecosystem function, and public health in the tropics.

RESúMEN: La contaminación ambiental por mercurio (Hg) en los trópicos supera nuestra comprensión de sus consecuencias para la biodiversidad. Los vacíos de conocimiento que existen sobre la exposición a la contaminación podrían ocultar las amenazas para la conservación en el Neotrópico: una región que alberga a más de la mitad de las especies del mundo, pero que enfrenta una continua intensificación de las emisiones de Hg y del cambio de uso del suelo por el avance de la minería de oro artesanal y de pequeña escala (MAPE). Debido a su distribución global y su sensibilidad a la contaminación, las aves brindan una oportunidad valiosa como bioindicadores para evaluar cómo las emisiones de Hg afectan la capacidad de un ecosistema para sustentar la biodiversidad y, en última instancia, la salud global. Presentamos la más grande base de datos sobre concentraciones de Hg en aves Neotropicales (n = 2,316) para establecer una línea base para los niveles de exposición a Hg en 322 especies de aves de nueve países de América Central, América del Sur, y el Caribe. Encontramos patrones de las concentraciones de Hg en aves de los trópicos que se asemejan a los de las regiones templadas: mostrando una bioacumulación consistente a través de grupos funcionales y una alta variación espaciotemporal. Las especies de aves que ocupan posiciones más altas en la cadena trófica y en hábitats acuáticos registraron concentraciones elevadas de Hg que podrían tener efectos negativos en su éxito reproductivo. Es importante resaltar que las concentraciones de Hg en las aves de los sitios afectados por la MAPE fueron cuatro veces más altas que las de los sitios control y además difirió por temporada para ciertos nichos tróficos. Desarrollamos esta síntesis a través de una red de investigación colaborativa, la Iniciativa de Investigación Tropical para la Conservación y Ecotoxicología Aviar (TRACE), que ejemplifica un intercambio de datos inclusivo, equitativo e internacional. Si bien nuestros hallazgos sugieren una necesidad urgente de evaluar los sesgos en el muestreo, los mecanismos, y las consecuencias de la exposición al Hg en las comunidades de aves tropicales, la Iniciativa TRACE proporciona un marco para abordar estos objetivos. Nuestro esfuerzo colectivo tiene como propósito respaldar y brindar información a las entidades locales, científicas, y gubernamentales, incluyendo las Partes de la Convención de Minamata de las Naciones Unidas sobre el Mercurio, mientras continuamos trabajando juntos para comprender cómo la contaminación por Hg en los trópicos puede afectar la salud pública, el funcionamiento de los ecosistemas, y la conservación de la biodiversidad. Total mercury (THg) concentrations (µg/g) and sample sizes of birds across Central America, South America, and the West Indies from 2007­2023. Point size and color are arranged in order of increasing THg concentration and hexagonal grid cells are colored in terms of increasing sample size.

Splice Junction Identification using Long Short-Term Memory Neural Networks.

Background: Splice junctions are the key to move from pre-messenger RNA to mature messenger RNA in many multi-exon genes due to alternative splicing. Since the percentage of multi-exon genes that undergo alternative splicing is very high, identifying splice junctions is an attractive research topic with important implications. Objective: The aim of this paper is to develop a deep learning model capable of identifying splice junctions in RNA sequences using 13,666 unique sequences of primate RNA. Methods: A Long Short-Term Memory (LSTM) Neural Network model is developed that classifies a given sequence as EI (Exon-Intron splice), IE (Intron-Exon splice), or N (No splice). The model is trained with groups of trinucleotides and its performance is tested using validation and test data to prevent bias. Results: Model performance was measured using accuracy and f-score in test data. The finalized model achieved an average accuracy of 91.34% with an average f-score of 91.36% over 50 runs. Conclusion: Comparisons show a highly competitive model to recent Convolutional Neural Network structures. The proposed LSTM model achieves the highest accuracy and f-score among published alternative LSTM structures.

Shallow Distance Dependence for Proton-Coupled Tyrosine Oxidation in Oligoproline Peptides.

We have explored the kinetic effect of increasing electron transfer (ET) distance in a biomimetic, proton-coupled electron-transfer (PCET) system. Biological ET often occurs simultaneously with proton transfer (PT) in order to avoid the high-energy, charged intermediates resulting from the stepwise transfer of protons and electrons. These concerted proton-electron-transfer (CPET) reactions are implicated in numerous biological ET pathways. In many cases, PT is coupled to long-range ET. While many studies have shown that the rate of ET is sensitive to the distance between the electron donor and acceptor, extensions to biological CPET reactions are sparse. The possibility of a unique ET distance dependence for CPET reactions deserves further exploration, as this could have implications for how we understand biological ET. We therefore explored the ET distance dependence for the CPET oxidation of tyrosine in a model system. We prepared a series of metallopeptides with a tyrosine separated from a Ru(bpy)32+ complex by an oligoproline bridge of increasing length. Rate constants for intramolecular tyrosine oxidation were measured using the flash-quench transient absorption technique in aqueous solutions. The rate constants for tyrosine oxidation decreased by 125-fold with three added proline residues between tyrosine and the oxidant. By comparison, related intramolecular ET rate constants in very similar constructs were reported to decrease by 4-5 orders of magnitude over the same number of prolines. The observed shallow distance dependence for tyrosine oxidation is proposed to originate in part from the requirement for stronger oxidants, leading to a smaller hole-transfer effective tunneling barrier height. The shallow distance dependence observed here and extensions to distance-dependent CPET reactions have potential implications for long-range charge transfers.

Immune-Mediated Control of a Dormant Neurotropic RNA Virus Infection.

Genomic material from many neurotropic RNA viruses (e.g., measles virus [MV], West Nile virus [WNV], Sindbis virus [SV], rabies virus [RV], and influenza A virus [IAV]) remains detectable in the mouse brain parenchyma long after resolution of the acute infection. The presence of these RNAs in the absence of overt central nervous system (CNS) disease has led to the suggestion that they are viral remnants, with little or no potential to reactivate. Here we show that MV RNA remains detectable in permissive mouse neurons long after challenge with MV and, moreover, that immunosuppression can cause RNA and protein synthesis to rebound, triggering neuropathogenesis months after acute viral control. Robust recrudescence of viral transcription and protein synthesis occurs after experimental depletion of cells of the adaptive immune response and is associated with a loss of T resident memory (Trm) lymphocytes within the brain. The disease associated with loss of immune control is distinct from that seen during the acute infection: immune cell-depleted, long-term-infected mice display severe gait and motor problems, in contrast to the wasting and lethal disease that occur during acute infection of immunodeficient hosts. These results illuminate the potential consequences of noncytolytic, immune-mediated viral control in the CNS and demonstrate that what were once considered "resolved" RNA viral infections may, in fact, induce diseases later in life that are distinct from those caused by acute infection.IMPORTANCE Viral infections of neurons are often not cytopathic; thus, once-infected neurons survive, and viral RNAs can be detected long after apparent viral control. These RNAs are generally considered viral fossils, unlikely to contribute to central nervous system (CNS) disease. Using a mouse model of measles virus (MV) neuronal infection, we show that MV RNA is maintained in the CNS of infected mice long after acute control and in the absence of overt disease. Viral replication is suppressed by the adaptive immune response; when these immune cells are depleted, viral protein synthesis recurs, inducing a CNS disease that is distinct from that observed during acute infection. The studies presented here provide the basis for understanding how persistent RNA infections in the CNS are controlled by the host immune response, as well as the pathogenic consequences of noncytolytic viral control.

The effects of climate, habitat, and trophic position on methylmercury bioavailability for breeding New York songbirds.

Mercury (Hg) is a global pollutant that affects songbird populations across a variety of ecosystems following conversion to methylmercury (MeHg)-a form of Hg with high potential for bioaccumulation and bioavailability. The amount of bioavailable MeHg in an ecosystem is a function of the amount of total Hg present as well as Hg methylation rates, which vary across the landscape in space and time, and trophic transfer. Using songbirds as an indicator of MeHg bioavailability in terrestrial ecosystems, we evaluated the role of habitat, climate, and trophic level in dictating MeHg exposure risk across a variety of ecosystems. To achieve this objective, 2243 blood Hg samples were collected from 81 passerine and near-passerine species in New York State, USA, spanning 10 different sampling regions from Long Island to western New York. Using a general linear mixed modeling framework that accounted for regional variation in sampling species composition, we found that wetland habitat area within 100 m of capture location, 50-year average of summer maximum temperatures, and trophic position inferred using stable isotope analysis were all correlated with songbird blood Hg concentrations statewide. Moreover, these patterns had a large degree of spatial variability suggesting that the drivers of MeHg bioavailability differed significantly across the state. Mercury deposition, land cover, and climate are all expected to change throughout the northeastern United States in the coming decades. Terrestrial MeHg bioavailability will likely respond to these changes. Focused research and monitoring efforts will be critical to understand how exposure risk responds to global environmental change across the landscape.

Long-term monitoring of mercury in adult saltmarsh sparrows breeding in Maine, Massachusetts and New York, USA 2000-2017.

Here we report on the results of a long-term study of mercury exposure in a songbird species, the saltmarsh sparrow (Ammodramus caudacutus). We measured total mercury concentrations in blood (n = 840) and feathers (n = 560) of adult saltmarsh sparrows at six locations between 2000 and 2017: Rachel Carson National Wildlife Refuge (RCNWR) in Wells, Maine; Scarborough Marsh State Wildlife Management Area in Scarborough, Maine; Parker River National Wildlife Refuge on Plum Island, Massachusetts; Pine Neck Preserve in Southampton, Long Island, New York; and North Cinder and North Green Sedge Islands off the coast of Long Island, New York. During the 12-17 year sampling periods, we found that mercury exposure differed by site and year but there was no consistent temporal trend across sites. Blood mercury concentrations declined only at RCNWR in Maine. We also found seasonal variation in blood mercury concentrations and a positive relationship between mercury concentrations of blood and innermost primary feather, but not between blood and tail feather.

Tissue and Bronchoalveolar Lavage Biomarkers in Idiopathic Pulmonary Fibrosis Patients on Pirfenidone.

BACKGROUND: Pirfenidone is a novel anti-fibrotic agent in idiopathic pulmonary fibrosis with proven clinical benefit. Better human tissue models to demonstrate the immunomodulatory and anti-fibrotic effect of pirfenidone are required. OBJECTIVES: The purpose of the study was to use transbronchial lung cryobiopsy (TBLC), a novel technique which provides substantial tissue samples, and a large panel of biomarkers to temporally assess disease activity and response to pirfenidone therapy. METHODS: Thirteen patients with confirmed idiopathic pulmonary fibrosis (IPF) underwent full physiological and radiological assessment at diagnosis and after 6-month pirfenidone therapy. They underwent assessment for a wide range of potential serum and bronchoalveolar lavage biomarkers of disease activity. Finally, they underwent TBLC before and after treatment. Tissue samples were assessed for numbers of fibroblast foci, for Ki-67, a marker of tissue proliferation and caspase-3, a marker of tissue apoptosis. RESULTS: All patients completed treatment and investigations without significant incident. There was no significant fall in number of fibroblast foci per unit tissue volume after treatment (pre-treatment: 0.14/mm2 vs. post-treatment 0.08/mm2, p = 0.1). Likewise, there was no significant change in other markers of tissue proliferation, Ki-67 or Caspase-3 with pirfenidone treatment. We found an increase in three bronchoalveolar lavage angiogenesis cytokines, Placental Growth Factor, Vascular Endothelial Growth Factor-A, and basic Fibroblast Growth Factor, two anti-inflammatory cytokines Interleukin-10 and Interleukin-4 and Surfactant Protein-D. CONCLUSIONS: TBLC offers a unique opportunity to potentially assess the course of disease activity and response to novel anti-fibrotic activity in IPF.

Exploring the solid state phase transition in dl-norvaline with terahertz spectroscopy.

dl-Norvaline is a molecular crystal at room temperature and it undergoes a phase transition when cooled below 190 K. This phase transition is believed to be Martensitic, thus making it of particular interest for molecular machines. In this paper we investigate this phase transition by measuring its terahertz (THz) spectrum over a range of temperatures. Temperature-dependent THz time-domain spectroscopy (THz-TDS) measurements reveal that the transition temperature (Tß→α) is 190 K. The influence of nucleation seeds was analyzed by determining the Tß→α of molecular crystals with varying grain size. Grains of 5 µm or less result in a lower transition temperature (Tß→α = 180 K) compared to larger grains of 125-250 µm (Tß→α = 190 K). Additionally, we gain insight into the physical process of the phase transition via temperature-dependent THz-TDS spectra of doped and mixed molecular crystals. The addition of molecular dopants, which differ from dl-norvaline only at the end of the side chain which resides in the hydrophobic layers of the crystal, decreases Tß→α. This is consistent with a solid-solid phase transition in which the unit cell shifts along this hydrophobic layer, and it leads us to believe that the phase transition in dl-norvaline is Martensitic in nature.

Pure Iterative Reconstruction Improves Image Quality in Computed Tomography of the Abdomen and Pelvis Acquired at Substantially Reduced Radiation Doses in Patients With Active Crohn Disease.

UNLABELLED: We assessed diagnostic accuracy and image quality of modified protocol (MP) computed tomography (CT) of the abdomen and pelvis reconstructed using pure iterative reconstruction (IR) in patients with Crohn disease (CD). METHODS: Thirty-four consecutive patients with CD were referred with suspected extramural complications. Two contemporaneous CT datasets were acquired in all patients: standard protocol (SP) and MP. The MP and SP protocols were designed to impart radiation exposures of 10% to 20% and 80% to 90% of routine abdominopelvic CT, respectively. The MP images were reconstructed with model-based IR (MBIR) and adaptive statistical IR (ASIR). RESULTS: The MP-CT and SP-CT dose length product were 88 (58) mGy.cm (1.27 [0.87] mSv) and 303 [204] mGy.cm (4.8 [2.99] mSv), respectively (P < 0.001). Median diagnostic acceptability, spatial resolution, and contrast resolution were significantly higher and subjective noise scores were significantly lower on SP-ASIR 40 compared with all MP datasets. There was perfect clinical agreement between MP-MBIR and SP-ASIR 40 images for detection of extramural complications. CONCLUSIONS: Modified protocol CT using pure IR is feasible for assessment of active CD.

Humour production may enhance observational learning of a new tool-use action in 18-month-old infants.

Many studies have shown that making children laugh enhances certain cognitive capacities such as attention, motivation, perception and/or memory, which in turn enhance learning. However, no study thus far has investigated whether laughing has an effect on learning earlier in infancy. The goal of this study was to see whether using humour with young infants in a demonstration of a complex tool-use task can enhance their learning. Fifty-three 18-month-old infants participated in this study and were included either in a humorous or a control demonstration group. In both groups infants observed an adult using a tool to retrieve an out-of-reach toy. What differed between groups was that in the humorous demonstration group, instead of playing with the toy, the adult threw it on the floor immediately after retrieval. The results show that infants who laughed at the demonstration in the humorous demonstration group reproduced significantly more frequent target actions than infants who did not laugh and those in the control group. This effect is discussed with regard to individual differences in terms of temperament and social capacities as well as positive emotion and dopamine release.

Economic implications of mercury exposure in the context of the global mercury treaty: Hair mercury levels and estimated lost economic productivity in selected developing countries.

Several developing countries have limited or no information about exposures near anthropogenic mercury sources and no studies have quantified costs of mercury pollution or economic benefits to mercury pollution prevention in these countries. In this study, we present data on mercury concentrations in human hair from subpopulations in developing countries most likely to benefit from the implementation of the Minamata Convention on Mercury. These data are then used to estimate economic costs of mercury exposure in these communities. Hair samples were collected from sites located in 15 countries. We used a linear dose-response relationship that previously identified a 0.18 IQ point decrement per part per million (ppm) increase in hair mercury, and modeled a base case scenario assuming a reference level of 1 ppm, and a second scenario assuming no reference level. We then estimated the corresponding increases in intellectual disability and lost Disability-Adjusted Life Years (DALY). A total of 236 participants provided hair samples for analysis, with an estimated population at risk of mercury exposure near the 15 sites of 11,302,582. Average mercury levels were in the range of 0.48 ppm-4.60 ppm, and 61% of all participants had hair mercury concentrations greater than 1 ppm, the level that approximately corresponds to the USA EPA reference dose. An additional 1310 cases of intellectual disability attributable to mercury exposure were identified annually (4110 assuming no reference level), resulting in 16,501 lost DALYs (51,809 assuming no reference level). A total of $77.4 million in lost economic productivity was estimated assuming a 1 ppm reference level and $130 million if no reference level was used. We conclude that significant mercury exposures occur in developing and transition country communities near sources named in the Minamata Convention, and our estimates suggest that a large economic burden could be avoided by timely implementation of measures to prevent mercury exposures.

Facet-dependent photoelectrochemical performance of TiO2 nanostructures: an experimental and computational study.

The behavior of crystalline nanoparticles depends strongly on which facets are exposed. Some facets are more active than others, but it is difficult to selectively isolate particular facets. This study provides fundamental insights into photocatalytic and photoelectrochemical performance of three types of TiO(2) nanoparticles with predominantly exposed {101}, {010}, or {001} facets, where 86-99% of the surface area is the desired facet. Photodegradation of methyl orange reveals that {001}-TiO(2) has 1.79 and 3.22 times higher photocatalytic activity than {010} and {101}-TiO(2), respectively. This suggests that the photochemical performance is highly correlated with the surface energy and the number of under-coordinated surface atoms. In contrast, the photoelectrochemical performance of the faceted TiO(2) nanoparticles sensitized with the commercially available MK-2 dye was highest with {010}-TiO(2) which yielded an overall cell efficiency of 6.1%, compared to 3.2% for {101}-TiO(2) and 2.6% for {001}-TiO(2) prepared under analogous conditions. Measurement of desorption kinetics and accompanying computational modeling suggests a stronger covalent interaction of the dye with the {010} and {101} facets compared with the {001} facet. Time-resolved THz spectroscopy and transient absorption spectroscopy measure faster electron injection dynamics when MK-2 is bound to {010} compared to other facets, consistent with extensive computational simulations which indicate that the {010} facet provides the most efficient and direct pathway for interfacial electron transfer. Our experimental and computational results establish for the first time that photoelectrochemical performance is dependent upon the binding energy of the dye as well as the crystalline structure of the facet, as opposed to surface energy alone.

Reduction of guide needle streak artifact in CT-guided biopsy.

PURPOSE: Computed tomography (CT)-guided core needle biopsy (CNB) can be affected by streak artifact obscuring the needle tip. This study investigates factors that influence the occurrence and severity of streak artifact during CNB. MATERIALS AND METHODS: Eight coaxial guide needles of two sizes from two manufacturers with and without stylets were imaged in a CT phantom, with CT reconstructed with adaptive statistical iterative reconstruction and filtered back projection. CNB-related streak artifact was quantified with profile analysis in an image-processing program. Differences between maximum attenuation at the needle tip and minimum attenuation in the streak artifact were compared for each variable. Diagnostic acceptability and streak artifact were subjectively assessed on each phantom image and on 40 clinical CNB procedures by three independent blinded reviewers following training case review. RESULTS: Artifact was significantly less with the central stylet removed versus in situ (median, 1,145 HU vs 3,390 HU; P < .001) for all needles, and less for 19-gauge needles versus 17-gauge needles (median, 1,334 HU vs 2,780 HU, respectively; P = .006). There were no differences based on manufacturer (P = .906) or reconstruction algorithm (P = .524). Independent reviews found that streak artifact was significantly reduced when the central stylet was removed (κ = 0.875-1.0; P < .001), and needle tip position was better in cases in which the stylet was removed (κ = 0.231-0.711; P < .001). CONCLUSIONS: Streak artifact can be reduced and needle tip visualization improved by confirming final biopsy needle position with the central stylet removed on CT and using smaller-gauge guide needles.

CNS recruitment of CD8+ T lymphocytes specific for a peripheral virus infection triggers neuropathogenesis during polymicrobial challenge.

Although viruses have been implicated in central nervous system (CNS) diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage. In this model, mice are infected with both CNS-restricted measles virus (MV) and peripherally restricted lymphocytic choriomeningitis virus (LCMV). While infection with either virus alone resulted in no illness, infection with both viruses caused disease in all mice, with ∼50% dying following seizures. Co-infection resulted in a 12-fold increase in the number of CD8+ T cells in the brain as compared to MV infection alone. Tetramer analysis revealed that a substantial proportion (>35%) of these infiltrating CD8+ lymphocytes were LCMV-specific, despite no detectable LCMV in CNS tissues. Mechanistically, CNS disease was due to edema, induced in a CD8-dependent but perforin-independent manner, and brain herniation, similar to that observed in mice challenged intracerebrally with LCMV. These results indicate that T cell trafficking can be influenced by other ongoing immune challenges, and that CD8+ T cell recruitment to the brain can trigger CNS disease in the apparent absence of cognate antigen. By extrapolation, human CNS diseases of unknown etiology need not be associated with infection with any particular agent; rather, a condition that compromises and activates the blood-brain barrier and adjacent brain parenchyma can render the CNS susceptible to pathogen-independent immune attack.

Positron emission tomography/computed tomography imaging in Merkel cell carcinoma: a study of 270 scans in 97 patients at the Dana-Farber/Brigham and Women's Cancer Center.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and lethal cutaneous neuroendocrine carcinoma. Imaging is crucial for accurate staging, which remains a strong predictor of survival, as well as earlier detection of recurrence and progression, which are common despite aggressive management. There is no consensus on the role of initial and subsequent imaging for MCC. OBJECTIVE: We sought to evaluate the use of 2-fluoro-[(18)F]-deoxy-2-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the management of MCC. METHODS: In all, 270 FDG-PET/CT studies were performed in 97 patients with pathology-proven MCC at the Dana-Farber/Brigham and Women's Cancer Center, Boston, Mass, from August 2003 to December 2010. RESULTS: FDG-PET/CT scans were obtained as part of the initial (61 scans in 61 patients) and subsequent (209 scans in 79 patients) treatment strategies. MCCs were FDG-avid with a mean maximum standardized uptake value of primary lesions of 6.5 (range 1.3-12.9) and a mean maximum standardized uptake value of regional and distant metastases of 7.2 (range 1.5-9.9). FDG-PET/CT upstaged 16% of patients who underwent baseline scans. FDG-PET/CT studies showed that bone and bone-marrow metastases were more common than previously reported, and were often undetected by CT. LIMITATIONS: Our study is limited by its retrospective design, and potential referral bias associated with a tertiary care center. CONCLUSIONS: FDG-PET/CT performed as part of the initial management strategy tended to upstage patients with more advanced disease. FDG-PET/CT performed as part of the subsequent treatment strategy identified metastatic disease, particularly in bone/bone marrow, which was not seen on CT. FDG-PET/CT imaging is a valuable staging and restaging tool in MCC management.

Controlling the pore sizes and related properties of inverse opal scaffolds for tissue engineering applications.

Inverse opal scaffolds are finding widespread use in tissue engineering and regenerative medicine. Herein, the way in which the pore sizes and related physical properties of poly(D,L-lactide-co-glycolide) inverse opal scaffolds are affected by the fabrication conditions is systematically investigated. It is found that the window size of an inverse opal scaffold is mainly determined by the annealing temperature rather than the duration of time, and the surface pore size is largely determined by the concentration of the infiltration solution. Although scaffolds with larger pore or window sizes facilitate faster migration of cells, they show slightly lower compressive moduli than scaffolds with smaller pore or window sizes.

Androgens repress expression of the F-box protein Skp2 via p107 dependent and independent mechanisms in LNCaP prostate cancer cells.

BACKGROUND: Androgens control homeostasis of the normal prostate and growth of prostate cancer (PCa) through the androgen receptor (AR) by regulating gene networks involving in cell proliferation, differentiation, and survival. We demonstrated previously that expression of Skp2, a key protein regulating cell entry into the S phase, is inhibited by androgens in an AR-dependent manner (Oncogene, 2004; 23(12): 2161-2176). However, the underlying mechanism of this regulation is unknown. METHODS: Using the LNCaP PCa cell line as a working model, the effect of androgens on the expression of Skp2 was examined by Western and Northern blot analyses. Cell cycle was measured by fluorescence-activated cell sorting (FACS). Gene transfection was performed by electroporation to manipulate the expression levels of proteins studied. RESULTS: At physiological levels androgens markedly repressed Skp2 expression but slightly induced Skp2 expression at subphysiological levels. Androgens modestly decreased the stability of the Skp2 protein. Androgenic repression of Skp2 expression was completely abolished by E1A-mediated inactivation of pocket proteins including RB, p130, and p107. Moreover, ectopic expression of p107 inhibited Skp2 expression, and silencing of p107 partially blocked androgenic repression of Skp2. CONCLUSIONS: Our data indicate that androgens repress Skp2 expression via p107-dependent and -independent pathways in PCa cells. These regulatory mechanisms may be targeted for the development of new therapeutics of androgen-refractory PCa.

PET/CT and renal pathology: a blind spot for radiologists? Part 1, primary pathology.

OBJECTIVE: PET/CT with (18)F-FDG shows metabolically active disease and is widely used for the diagnosis and follow-up of patients with cancer. Nonmetabolically active renal pathology may be missed without close attention to the CT portion of the study, whereas metabolically active pathology may be missed on PET because of physiologic tracer excretion in the kidneys. This article illustrates primary lesions of the kidney on FDG PET/CT with emphasis on key anatomic features and the appearance of tracer uptake. CONCLUSION: Close attention to both the FDG PET and CT portions of the study is essential to interpret renal pathology correctly on FDG PET/CT examinations.

PET/CT and renal pathology: a blind spot for radiologists? Part 2--lymphoma, leukemia, and metastatic disease.

OBJECTIVE: PET/CT with (18)F-FDG is a powerful tool to evaluate patients with hematologic malignancy or to assess the burden of metastatic disease from solid tumors. Metabolically active renal pathology associated with lymphoma, leukemia, or metastatic disease can be missed without close attention to both the PET and CT portions of the study because of physiologic FDG excretion in the kidneys. This article illustrates the appearance of tracer uptake and the key anatomic features of lymphoma, leukemia, and metastatic disease involving the kidney on FDG PET/CT. CONCLUSION: Close attention to both the FDG PET and CT portions of an FDG PET/CT study is essential to evaluate the kidneys in oncology patients.