Oxidative stress-dependent cyclooxygenase-2-derived prostaglandin f(2α) impairs endothelial function in renovascular hypertensive rats.
Abstract Aims: The role of endothelium-derived contracting factors (EDCFs) in regulating renovascular function is yet to be elucidated in renovascular hypertension (RH). The current study investigated whether oxidative stress-dependent cyclooxygenase (COX)-2-derived prostaglandin F(2α) (PGF(2α)) impairs endothelial function in renal arteries of renovascular hypertensive rats (RHR). Renal hypertension was induced in rats by renal artery stenosis of both kidneys using the 2-kidney 2-clip model. Acute treatment with reactive oxygen species (ROS) scavengers, COX-2 inhibitors, and thromboxane-prostanoid receptor antagonists, but not COX-1 inhibitors, improved endothelium-dependent relaxations and eliminated endothelium-dependent contractions in RHR renal arteries. Five weeks of treatment with celecoxib or tempol reduced blood pressure, increased renal blood flow, and restored endothelial function in RHRs. Increased ROS production in RHR arteries was inhibited by ROS scavengers, but unaffected by COX-2 inhibitors; whereas increased PGF(2α) release was reduced by both ROS scavengers and COX-2 inhibitors. ROS also induced COX-2-dependent contraction in RHR renal arteries, which was accompanied by the release of COX-2-derived PGF(2α). Further, chronic tempol treatment reduced COX-2 and BMP4 upregulation, p38MAPK phosphorylation, and the nitrotyrosine level in RHR renal arteries. These findings demonstrate the functional importance of oxidative stress, which serves as an initiator of increased COX-2 activity, and that COX-2-derived PGF(2α) plays an important role in mediating endothelial dysfunction in RH. The current study, thus, suggests that drugs targeting oxidative stress-dependent COX-2-derived PGF(2α) may be useful in the prevention and management of RH. Antioxid. Redox Signal. 16, 363-373.


Association of anthropometric measures and cardiovascular risk factors in children and adolescents: Findings from the Aboriginal Birth Cohort study.
This study examined the association of anthropometric measures including height, leg length, trunk length and body mass index (BMI) at 11 and 18 years with systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) at 11 and 18 years. We analysed data from 661 participants from the Aboriginal Birth Cohort study-a longitudinal study based in the Northern Territory, Australia. Associations between anthropometric measures and cardiovascular risk factors were investigated in linear regression analyses adjusted for confounding, with imputation for missing data. In adjusted analyses, increasing leg length [males: 0.47mmHg/cm (0.23, 0.72); females: 0.50mmHg/cm (0.18, 0.83)], trunk length [males: 0.50mmHg/cm (0.28, 0.73); females: 0.57mmHg/cm (0.33, 0.81)] and height [males: 0.32mmHg/cm (0.16, 0.48); females: 0.32mmHg/cm (0.12, 0.52)] at 11 years was associated with higher SBP at 11 years. When these exposures were measured at 18 years the effect on SBP at 18 years had attenuated, and only increased trunk length was associated with higher SBP at 18 years for both sexes [males: 0.46mmHg/cm (0.05, 0.87); females: 0.69mmHg/cm (0.30, 1.08)]. We observed little association between height, leg length and trunk length and DBP, total cholesterol, LDL-c and HDL-c. Increased BMI was associated with elevated SBP and DBP at 11 and 18 years. Our findings suggest that height, leg length, and trunk length measured at 11 and 18 years was generally not associated with cardiovascular risk factors at 11 and 18 years. However, greater childhood BMI was associated with higher blood pressure and this association persisted into adolescence. This study contributes to the limited body of evidence on the association between measures of early anthropometry and cardiovascular risk among the Australian Aboriginal population.


Concurrent visual and acoustic tracking of passive and active delivery of nanobubbles to tumors.
Background: There has been growing interest in nanobubbles for their potential to extend bubble-mediated ultrasound approaches beyond that of their larger microbubble counterparts. In particular, the smaller scale of nanobubbles may enable them to access the tumor extravascular compartment for imaging and therapy in closer proximity to cancer cells. Compelling preliminary demonstrations of the imaging and therapeutic abilities of nanobubbles have thus emerged, with emphasis on their ability to extravasate. However, studies to date rely on indirect histologic evidence that cannot confirm whether the structures remain intact beyond the vasculature - leaving their extravascular potential largely untapped. Methods: Nanobubble acoustic scattering was assessed using a recently reported ultra-stable formulation at low concentration (106 mL-1) and frequency (1 MHz), over a range of pressures (100-1500 kPa) in a channel phantom. The pressure-dependent response was utilized as a basis for in vivo experiments where ultrasound transmitters and receivers were integrated into a window chamber for simultaneous intravital multiphoton microscopy and acoustic monitoring in tumor-affected microcirculation. Microscopy and acoustic data were utilized to assess passive and active delivery of nanobubbles and determine whether they remained intact beyond the vasculature. Results: Nanobubbles exhibit pressure-dependent nonlinear acoustic scattering. Nanobubbles are also found to have prolonged acoustic vascular pharmacokinetics, and passively extravasate intact into tumors. Ultrasound stimulation of nanobubbles is shown to actively enhance the delivery of both intact nanobubbles and shell material, increasing their spatial bioavailability deeper into the extravascular space. A range of acute vascular effects were also observed. Conclusion: This study presents the first direct evidence that nanobubbles passively and actively extravasate intact in tumor tissue, and is the first to directly capture acute vascular events from ultrasound-stimulation of nanobubbles. The insights gained here demonstrate an important step towards unlocking the potential of nanobubbles and extending ultrasound-based applications.


Surface effects of vapour-liquid-solid driven Bi surface droplets formed during molecular-beam-epitaxy of GaAsBi.
Herein we investigate a (001)-oriented GaAs1-xBix/GaAs structure possessing Bi surface droplets capable of catalysing the formation of nanostructures during Bi-rich growth, through the vapour-liquid-solid mechanism. Specifically, self-aligned "nanotracks" are found to exist trailing the Bi droplets on the sample surface. Through cross-sectional high-resolution transmission electron microscopy the nanotracks are revealed to in fact be elevated above surface by the formation of a subsurface planar nanowire, a structure initiated mid-way through the molecular-beam-epitaxy growth and embedded into the epilayer, via epitaxial overgrowth. Electron microscopy studies also yield the morphological, structural, and chemical properties of the nanostructures. Through a combination of Bi determination methods the compositional profile of the film is shown to be graded and inhomogeneous. Furthermore, the coherent and pure zincblende phase property of the film is detailed. Optical characterisation of features on the sample surface is carried out using polarised micro-Raman and micro-photoluminescence spectroscopies. The important light producing properties of the surface nanostructures are investigated through pump intensity-dependent micro-PL measurements, whereby relatively large local inhomogeneities are revealed to exist on the epitaxial surface for important optical parameters. We conclude that such surface effects must be considered when designing and fabricating optical devices based on GaAsBi alloys.


A comprehensive review of the sinuvertebral nerve with clinical applications.
The anatomy and clinical significance of the sinuvertebral nerve is a topic of considerable interest among anatomists and clinicians, particularly its role in discogenic pain. It has required decades of research to appreciate its role, but not until recently could these studies be compiled to establish a more complete description of its clinical significance. The sinuvertebral nerve is a recurrent nerve that originates from the ventral ramus, re-entering the spinal canal via the intervertebral foramina to innervate multiple meningeal and non-meningeal structures. Its complex anatomy and relationship to discogenic pain have warranted great interest among clinical anatomists owing to its sympathetic contribution to the lumbar spine. Knowledge of the nerve has been used to design a variety of diagnostic and treatment procedures for chronic discogenic pain. This paper reviews the anatomy and clinical aspects of the sinuvertebral nerve.


Role of Nrf2 and Autophagy in Acute Lung Injury.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the clinical manifestations of severe lung damage and respiratory failure. Characterized by severe inflammation and compromised lung function, ALI/ARDS result in very high mortality of affected individuals. Currently, there are no effective treatments for ALI/ARDS, and ironically, therapies intended to aid patients (specifically mechanical ventilation, MV) may aggravate the symptoms. Key events contributing to the development of ALI/ARDS are: increased oxidative and proteotoxic stresses, unresolved inflammation, and compromised alveolar-capillary barrier function. Since the airways and lung tissues are constantly exposed to gaseous oxygen and airborne toxicants, the bronchial and alveolar epithelial cells are under higher oxidative stress than other tissues. Cellular protection against oxidative stress and xenobiotics is mainly conferred by Nrf2, a transcription factor that promotes the expression of genes that regulate oxidative stress, xenobiotic metabolism and excretion, inflammation, apoptosis, autophagy, and cellular bioenergetics. Numerous studies have demonstrated the importance of Nrf2 activation in the protection against ALI/ARDS, as pharmacological activation of Nrf2 prevents the occurrence or mitigates the severity of ALI/ARDS. Another promising new therapeutic strategy in the prevention and treatment of ALI/ARDS is the activation of autophagy, a bulk protein and organelle degradation pathway. In this review, we will discuss the strategy of concerted activation of Nrf2 and autophagy as a preventive and therapeutic intervention to ameliorate ALI/ARDS.


Low-Cost 3D Printers Enable High-Quality and Automated Sample Preparation and Molecular Detection.
Most molecular diagnostic assays require upfront sample preparation steps to isolate the target's nucleic acids, followed by its amplification and detection using various nucleic acid amplification techniques. Because molecular diagnostic methods are generally rather difficult to perform manually without highly trained users, automated and integrated systems are highly desirable but too costly for use at point-of-care or low-resource settings. Here, we showcase the development of a low-cost and rapid nucleic acid isolation and amplification platform by modifying entry-level 3D printers that cost between $400 and $750. Our modifications consisted of replacing the extruder with a tip-comb attachment that houses magnets to conduct magnetic particle-based nucleic acid extraction. We then programmed the 3D printer to conduct motions that can perform high-quality extraction protocols. Up to 12 samples can be processed simultaneously in under 13 minutes and the efficiency of nucleic acid isolation matches well against gold-standard spin-column-based extraction technology. Additionally, we used the 3D printer's heated bed to supply heat to perform water bath-based polymerase chain reactions (PCRs). Using another attachment to hold PCR tubes, the 3D printer was programmed to automate the process of shuttling PCR tubes between water baths. By eliminating the temperature ramping needed in most commercial thermal cyclers, the run time of a 35-cycle PCR protocol was shortened by 33%. This article demonstrates that for applications in resource-limited settings, expensive nucleic acid extraction devices and thermal cyclers that are used in many central laboratories can be potentially replaced by a device modified from inexpensive entry-level 3D printers.


The biographical impact of teenage and adolescent cancer.
This paper offers an overview of the findings of research into the experience of having cancer in adolescence and young adulthood, the aims of which were to understand how age and life stage affect the illness experience and impact upon biographies and life trajectories. The data were gathered primarily through the use of in-depth qualitative interviews with adolescents and young adults with cancer, but also through the submission of a small number of written narratives. Acute and life-threatening illness at a transitional life stage on the threshold of adulthood can have a long-term, and therefore chronic, effect on the life trajectories and biographies of young adult cancer patients. Many aspects of the participants' lives were affected, including education, careers, life plans, friendship networks, appearance, sexuality and fertility. The economic effects could also be far-reaching and contribute to a loss of independence, which is very fragile in this age-group. While recognizing the potentially devastating impact of cancer at any age, the research findings suggest a distinct effect in adolescence and young adulthood resulting from a disrupted biography at a critical transitional moment in the life trajectory that can have a chronic effect after the acute stage of the illness is passed. An age-appropriate approach to the care of young people with cancer that takes into account the distinct effects of life stage in this age-group can mitigate the negative impact on life trajectories and maximize the chances of adherence and a return to normal life after recovery.


Determinants of Length of Stay Following Total Anterior Circulatory Stroke.
Identification of factors that determine length of stay (LOS) in total anterior circulatory stroke (TACS) has potential for targeted intervention to reduce the associated health care burden. This study aimed to determine which factors predict LOS following either ischaemic or haemorrhagic TACS. The study sample population was drawn from the Norfolk and Norwich Stroke and Transient Ischemic Attack (TIA) Register (1996⁻2012), a prospective registry. 2965 patients admitted with TACS verified by a stroke specialist team were included. Primary analysis identified predictors of length of stay (LOS) in either haemorrhagic or ischaemic TACS. Secondary analyses identified predictors of LOS in patients who were discharged alive or who died during admission separately. Moderate (p = 0.014) to severe disability (p = 0.015) and history of congestive heart failure (p = 0.027) in the primary analysis and pre-stroke residence in a care facility among patients who survived to discharge (p = 0.013) were associated with a shorter length of stay. Factors associated with increased length of stay included presence of neurological lateralisation in the primary analysis (p = 0.004) and amongst patients who died (p = 0.003 and p = 0.014 for ischaemic and haemorrhagic stroke, respectively). Patients with advanced age (≥85 years) with haemorrhagic stroke had longer LOS regardless of mortality outcome. Patients with low pre-morbid disability (modified Rankin score ≤2 who died following haemorrhagic TACS also had longer LOS. Our study found predictors of LOS following TACS include neurological lateralisation, pre-stroke disability status, congestive heart failure, pre-morbid residence and age. The identification of such factors would assist in resource allocation and discharge planning.


Single-spanning membrane protein insertion in membrane mimetic systems: role and localization of aromatic residues.
Membrane protein insertion in the lipid bilayer is determining for their activity and is governed by various factors such as specific sequence motifs or key amino-acids. A detailed fluorescence study of such factors is exemplified with PMP1, a small (38 residues) single-membrane span protein that regulates the plasma membrane H(+)-ATPase in yeast and specifically interacts with phosphatidylserines. Such interactions may stabilize raft domains that have been shown to contain H(+)-ATPase. Previous NMR studies of various fragments have focused on the critical role of interfacial residues in the PMP1 structure and intermolecular interactions. The C-terminal domain contains a terminal Phe (F38), a single Trp (W28) and a single Tyr (Y25) that may act together to anchor the protein in the membrane. In order to describe the location and dynamics of W28 and the influence of Y25 on protein insertion within membrane, we carried out a detailed steady-state and time-resolved fluorescence study of the synthetic G13-F38 fragment and its Tyr-less mutant, Y25L in various membrane mimetic systems. Detergent micelles are conveniently used for this purpose. We used dodecylphosphocholine (DPC) in order to compare with and complement previous NMR results. In addition, dodecylmaltoside (DM) was used so that we could apply our recently described new quenching method by two brominated analogs of DM (de Foresta et al. 2002, Eur. Biophys. J. 31:185-97). In both systems, and in the presence and absence of Y25, W28 was shown to be located below but close to the polar headgroup region, as shown by its maximum emission wavelengths (lambda(max)), curves for the quenching of Trp by the brominated analogs of DM and bimolecular constants for quenching (k(q)) by acrylamide. Results were interpreted by comparison with calibration data obtained with fluorescent model peptides. Time-resolved anisotropy measurements were consistent with PMP1 fragment immobilization within peptide-detergent complexes. We tentatively assigned the two major Trp lifetimes to the Trp (chi(1)=60 degrees and 180 degrees ) rotamers, based on the recent lifetime-rotamer correlation proposed for model cyclic peptides (Pan and Barkley 2004, Biophys J 86:3828-35). We also analyzed the role of the hydrophobic anchor, by comparing the micelle binding of fragments of various lengths including the synthesized full-length protein and detected peculiar differences for protein interaction with the polar headgroups of DM or DPC.


Adiponectin upregulates prolyl-4-hydroxylase α1 expression in interleukin 6-stimulated human aortic smooth muscle cells by regulating ERK 1/2 and Sp1.
Adiponectin is an anti-atherogenic adipokine that inhibits the development of plaque by mechanisms that are not completely understood. Extracellular matrix (ECM) may have a role in the pathogenesis of atherosclerosis. We explored the effect and mechanisms of adiponectin on the synthesis of prolyl-4-hydroxylase (P4H) in interleukin 6 (IL-6)-stimulated human aortic smooth muscle cells (HASMCs). P4Hα1 mRNA level was quantified by RT-PCR, the protein levels of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and P4Hα1 were quantified by western blot analysis, and activation of specific protein 1 (Sp1) was determined by electrophoretic mobility shift assay and subcellular localization of Sp1 by immunofluorescence analysis. Adiponectin significantly increased P4Hα1 mRNA and protein levels in IL-6-stimulated HASMCs in a dose- and time-dependent manner. As well, ERK1/2 and Sp1 played a crucial role in the effect of adiponectin upregulating P4Hα1 expression in IL-6-stimulated HASMCs. Adiponectin abrogated the effects of IL-6 on collagen III level, which may indicate that P4Hα1 is essential for folding the procollagen polypeptide chains into stabilized collagen. Adiponectin attenuates IL-6-inhibited P4Hα1 synthesis and stabilizes collagen formation in HASMCs through a Sp1-ERK1/2-P4Hα1-dependent pathway.


Open Science Badges in the Journal of Neurochemistry.
The Open Science Framework (OSF) has the mission to increase openness, integrity, and reproducibility in research. The Journal of Neurochemistry became a signatory of their Transparency and Openness guidelines in 2016, which provides eight modular standards (Citation standards, Data Transparency, Analytic Methods/Code Transparency, Research Materials Transparency, Design and Analysis Transparency, Study Pre-registration, Analysis Plan Transparency, Replication) with increasing levels of stringency. Furthermore, OSF recommends and offers a collection of practices intended to make scientific processes and results more transparent and available in a standardized way for reuse to people outside the research team. It includes making research materials, data, and laboratory procedures freely accessible online to anyone. This editorial announces the decision of the Journal of Neurochemistry to introduce Open Science Badges, maintained by the Open Science Badges Committee and by the Center for Open Science (COS). The Open Science Badges, visual icons placed on publications, certify that an open practice was followed and signal to readers that an author has shared the corresponding research evidence, thus, allowing an independent researcher to understand how to reproduce the procedure.


Food security is related to adult type 2 diabetes control over time in a United States safety net primary care clinic population.
Successful Type 2 diabetes management requires adopting a high nutrient-density diet made up of food items that both meet dietary needs and preferences and can be feasibly obtained on a regular basis. However, access to affordable, nutrient-dense foods often is lacking in poorer neighbourhoods. Therefore, low food security should directly impair glucose control, even when patients have full access to and utilize comprehensive medical management. The present study sought to determine whether food security is related longitudinally to glucose control, over-and-above ongoing medication management, among Type 2 diabetes patients receiving comprehensive care at a Midwestern multi-site federally qualified health centre (FQHC). In this longitudinal observational study, we completed a baseline assessment of patients' food security (using the US Household Food Security Module), demographics (via Census items), and diabetes history/management (using a structured clinical encounter form) when patients began receiving diabetes care at the health centre. We then recorded those patients' A1C levels several times during a 24-month follow-up period. Three hundred and ninety-nine patients (56% with low food security) had a baseline A1c measurement; a subsample of 336 (median age=52 years; 56% female; 60% Hispanic, 27% African American, and 9% White) also had at least one follow-up A1c measurement. Patients with lower (vs higher) food security were more likely to be on insulin and have higher A1c levels at baseline. Moreover, the disparity in glucose control by food security status persisted throughout the next 2 years. Although results were based on one multi-site FQHC, potentially limiting their generalizability, they seem to suggest that among Type 2 diabetes patients, low food security directly impairs glucose control-even when patients receive full access to comprehensive medical management-thereby increasing their long-term risks of high morbidity, early mortality, and high health-care utilization and cost.


Cancer trials versus the real world in the United States.
Federal policies have been implemented to mitigate underenrollment in cancer trials in the United States. We sought to identify patterns and predictors of enrollment patterns to cancer trials in a contemporary era using a real world setting. The 2001-2008 California Cancer Registry was used to determine patterns and predictors of enrollment in clinical trials for stage 0 to IV solid organ malignant tumors. Multivariate techniques were used to identify predictors of enrollment in cancer protocols, controlling for covariates. Less than a percent (0.64%) of patients enrolled in clinical trials (1566 of 244,528). Black patients were less likely than whites to enroll in trials (0.48% vs 0.67%, P < 0.05). On multivariate analysis, older persons (>65 years), early stage cancer, and those with lung or gastrointestinal cancers were less likely to be enrolled in cancer trials. Results were consistent when evaluated among only nonbreast cancer protocols. Though approaching significance, black, underinsured, and uninsured patients showed trends toward underenrollment. In addition to profoundly low overall cancer trial accrual, vast underrepresentation by age, cancer stage, and site continue to exist. The generalizability of these trials to a real world perspective remains an open question. Physicians, payers, the National Cancer Institute, and other stakeholders need to develop broader cancer trials to benefit the millions of patients with cancer in the United States.


Stroke preceding autoimmune encephalitis with neuronal potassium channel antibody.
Autoimmune encephalitis related to voltage-gated potassium channel (VGKC) antibodies can occur as a complication of cancer but, more frequently, as a non-paraneoplastic disorder. The prompt recognition and treatment could mitigate the morbidity associated with this entity, but the broad-spectrum of neurological manifestations often makes the diagnosis a challenge. The authors describe, here, a unique case of autoimmune encephalitis related to VGKC antibodies preceded by an ischaemic stroke. Conditions associated with the stroke (infection, seizures, metabolic disturbances) had delayed the diagnosis. The authors suggest that autoimmune encephalitis needs to be taken into consideration as part of a differential diagnosis in patients with prolonged encephalopathy following an ischaemic stroke. Infection may trigger an inflammatory response. In addition, the rupture of blood brain barrier that occurs in stroke may have a pathogenic role by allowing antibodies to gain access to the central nervous system.


Parallel Algorithm for GPU Processing; for use in High Speed Machine Vision Sensing of Cotton Lint Trash.
One of the main hurdles standing in the way of optimal cleaning of cotton lint isthe lack of sensing systems that can react fast enough to provide the control system withreal-time information as to the level of trash contamination of the cotton lint. This researchexamines the use of programmable graphic processing units (GPU) as an alternative to thePC's traditional use of the central processing unit (CPU). The use of the GPU, as analternative computation platform, allowed for the machine vision system to gain asignificant improvement in processing time. By improving the processing time, thisresearch seeks to address the lack of availability of rapid trash sensing systems and thusalleviate a situation in which the current systems view the cotton lint either well before, orafter, the cotton is cleaned. This extended lag/lead time that is currently imposed on thecotton trash cleaning control systems, is what is responsible for system operators utilizing avery large dead-band safety buffer in order to ensure that the cotton lint is not undercleaned.Unfortunately, the utilization of a large dead-band buffer results in the majority ofthe cotton lint being over-cleaned which in turn causes lint fiber-damage as well assignificant losses of the valuable lint due to the excessive use of cleaning machinery. Thisresearch estimates that upwards of a 30% reduction in lint loss could be gained through theuse of a tightly coupled trash sensor to the cleaning machinery control systems. Thisresearch seeks to improve processing times through the development of a new algorithm forcotton trash sensing that allows for implementation on a highly parallel architecture.Additionally, by moving the new parallel algorithm onto an alternative computing platform,the graphic processing unit "GPU", for processing of the cotton trash images, a speed up ofover 6.5 times, over optimized code running on the PC's central processing unit "CPU", wasgained. The new parallel algorithm operating on the GPU was able to process a 1024x1024image in less than 17ms. At this improved speed, the image processing system's performance should now be sufficient to provide a system that would be capable of realtimefeed-back control that is in tight cooperation with the cleaning equipment.


Characterization of gene expression on genomic segment 7 of infectious salmon anaemia virus.
Infectious salmon anaemia (ISA) virus (ISAV), an important pathogen of fish that causes disease accompanied by high mortality in marine-farmed Atlantic salmon, is the only species in the genus Isavirus, one of the five genera of the Orthomyxoviridae family. The Isavirus genome consists of eight single-stranded RNA species, and the virions have two surface glycoproteins; haemagglutinin-esterase (HE) protein encoded on segment 6 and fusion (F) protein encoded on segment 5. Based on the initial demonstration of two 5'-coterminal mRNA transcripts by RT-PCR, ISAV genomic segment 7 was suggested to share a similar coding strategy with segment 7 of influenza A virus, encoding two proteins. However, there appears to be confusion as to the protein sizes predicted from the two open reading frames (ORFs) of ISAV segment 7 which has in turn led to confusion of the predicted protein functions. The primary goal of the present work was to clone and express these two ORFs in order to assess whether the predicted protein sizes match those of the expressed proteins so as to clarify the coding assignments, and thereby identify any additional structural proteins of ISAV. In the present study we show that ISAV segment 7 encodes 3 proteins with estimated molecular masses of 32, 18, and 9.5 kDa. The 18-kDa and 9.5-kDa products are based on removal of an intron each from the primary transcript (7-ORF1) so that the translation continues in the +2 and +3 reading frames, respectively. The segment 7-ORF1/3 product is variably truncated in the sequence of ISAV isolates of the European genotype. All three proteins are recognized by rabbit antiserum against the 32-kDa product of the primary transcript, as they all share the N-terminal 22 amino acids. This antiserum detected a single 35-kDa protein in Western blots of purified virus, and immunoprecipitated a 32-kDa protein in ISAV-infected TO cells. Immunofluorescence staining of infected cells with the same antiserum revealed the protein(s) to be localized in the cytoplasm. Vaccination of farmed Atlantic salmon with the 32-kDa protein resulted in a higher survival rate than what was attainable with the HE protein, albeit a moderate protection against the low ISAV challenge. Collectively, our observations suggest that the product of ISAV segment 7 primary transcript (7-ORF1) is a structural protein. The 18-kDa (7-ORF1/2) protein is identified as the putative ISAV nuclear export protein based on the presence of nuclear export signals. The function of the 9.5-kDa (7-ORF1/3) protein is not presently known.


Vision method of inspecting missing fastening components in high-speed railway.
The increasing train speed on railways generates an urgent need for more powerful automatic inspection of railway tracks, including real-time fastening component inspection. To obtain better high-speed performance with lower cost, this paper has proposed a novel structured light method based on motion image (SLMMI) for moving object inspection. The motion images in the proposed method are insensitive to motion, abundant with information, and easy to process, resulting in a low performance requirement of the hardware. Compared to the conventional unstructured light method and structured light method, the proposed method inherits the virtues of both thus offering a fresh perspective when inspecting missing fastening components on high-speed railways. By using the SLMMI and the recognition method based on a neural network, the experimental results yield good performance in terms of speed and accuracy. Furthermore, the robustness of the proposed method is also discussed and simulated by adding typical interferences, such as ambient light, vibration, and obstacles.


Validation of the World Health Organization Assessment Schedule II Chinese Traditional Version (WHODAS II CT) in persons with disabilities and chronic illnesses for Chinese population.
The aim of this study is to test the psychometric properties and validity of the World Health Organization Assessment Schedule II Chinese Traditional Version (WHODAS II CT) in Traditional Chinese-speaking persons with disabilities and chronic illnesses. The WHODAS II CT has been administrated to a sample of 1020 persons with disabilities and chronic illnesses. The construct validity, internal consistency, concurrent validity and convergent validity were evaluated. WHODAS II CT showed a satisfactory model fit for the second-order confirmatory factor analysis model (χ(2)/df = 3.05, root means square error of approximation = 0.053, comparative fit index = 0.912, standardized root mean square residual = 0.076), high internal consistency (Cronbach's α = 0.98), high correlation with all domains of Dartmouth Primary Care Cooperative Research Network/World Organization of National Colleges, Academies, and Academic Associations of General Practices/Family Physicians (COOP/WONCA) charts (partial correlation coefficient ranged from 0.26 to 0.74) and significance between persons with and without co-morbidity (all regression coefficients >0). WHODAS II CT is a reliable and valid instrument to measure the disability in persons with disabilities and chronic illnesses among Traditional Chinese-speaking population. A further study is required to validate the short version of WHODAS II in order to enhance its applicability in usual and clinical practices. Implications for Rehabilitation This is the first study to evaluate the reliability and validity of WHODAS II in persons with disability and chronic illnesses among Traditional Chinese-speaking population. The WHODAS II CT is a valid instrument in Chinese adults with disabilities and chronic illnesses. The WHODAS II CT is recommended to be used in population-based survey to investigate the health needs of persons with disabilities and chronic illnesses as well as in the rehabilitation programs as an outcome measure.


The Atlantic Bonito (Sarda sarda, Bloch 1793) transcriptome and detection of differential expression during larvae development.
The Atlantic bonito (Sarda sarda, Bloch 1793) belongs to the important marine fish species with a wide geographical distribution covering the Atlantic Ocean, the Mediterranean and its bordering seas. Aquaculture practices for this species are still in their infancies and scientific studies are seldom undertaken, mainly because of difficulties in sampling. Thus for small tuna species like the Atlantic bonito only little is known about its biology and regarding the molecular background even less information is available. In the production of marine fish it is known that the most critical period is the larval stages, as high growth rates as well as significant developmental changes take place. In this study we have investigated the transcriptome of the Atlantic bonito of five larvae stages applying Illumina sequencing technology. For non-model species like aquaculture species, transcriptome analysis of RNA samples from individuals using Illumina sequencing technology is technically efficient and cost effective. In the present study a total number of 169,326,711 paired-end reads with a read length of 100 base pairs were generated resulting in a reference transcriptome of 68,220 contigs with an average length of 2054 base pairs. For differential expression analyses single end reads were obtained from different developmental stages and mapped to the constructed reference transcriptome. Differential expression analyses revealed in total 18,657 differentially expressed transcripts and were assigned to five distinguished groups. Each of the five clusters shows stage specific gene expression. We present for the first time in the Atlantic bonito an extensive RNA-Seq based characterization of its transcriptome as well as significant information on differential expression among five developmental larvae stages. The generated transcripts, including SNP and microsatellite information for candidate molecular markers and gene expression information will be a valuable resource for future genetic and molecular studies.


The association of physical deconditioning and chronic low back pain: a hypothesis-oriented systematic review.
Does physical deconditioning (loss of cardiovascular capacity and strength/endurance of paraspinal muscles) exist in patients with chronic low back pain (CLBP) and are treatments specifically aimed to reduce these signs effective? Systematic literature search in PUBMED, MEDLINE, EMBASE and PsycINFO until December 2004 to identify observational studies regarding deconditioning signs and high quality RCTs regarding the effectiveness of cardiovascular and/or muscle strengthening exercises. Internal validity of the RCTs was assessed by using a checklist of nine methodology criteria in accordance with the Cochrane Collaboration. There is conflicting evidence that cardiovascular deconditioning is present in CLBP and limited evidence for wasting of the multifidus muscle. No study examined the effectiveness of cardiovascular training specifically. General and lumbar muscle strengthening are equally effective as other active treatments. Only moderate evidence is available for the effectiveness of intensive low back extensor muscle strengthening compared to less intensive strengthening. Probably reactivation caused by active treatment and not the reconditioning itself is the important factor in the reduction of disability. Further prospective and evaluative research into the role of physical deconditioning is necessary. It seems more promising to further explore the interplay between biological, social and psychological factors.


Unintended pregnancy and abortion in Uganda.
Unintended pregnancy is common in Uganda, leading to high levels of unplanned births, unsafe abortions, and maternal injury and death. Because most pregnancies that end in abortion are unwanted, nearly all ill health and mortality resulting from unsafe abortion is preventable. This report summarizes evidence on the context and consequences of unintended pregnancy and unsafe abortion in Uganda, points out gaps in knowledge, and highlights steps that can be taken to reduce levels of unintended pregnancy and unsafe abortion, and, in turn, the high level of maternal mortality.


Proteolytic elimination of N-myristoyl modifications by the Shigella virulence factor IpaJ.
Protein N-myristoylation is a 14-carbon fatty-acid modification that is conserved across eukaryotic species and occurs on nearly 1% of the cellular proteome. The ability of the myristoyl group to facilitate dynamic protein-protein and protein-membrane interactions (known as the myristoyl switch) makes it an essential feature of many signal transduction systems. Thus pathogenic strategies that facilitate protein demyristoylation would markedly alter the signalling landscape of infected host cells. Here we describe an irreversible mechanism of protein demyristoylation catalysed by invasion plasmid antigen J (IpaJ), a previously uncharacterized Shigella flexneri type III effector protein with cysteine protease activity. A yeast genetic screen for IpaJ substrates identified ADP-ribosylation factor (ARF)1p and ARF2p, small molecular mass GTPases that regulate cargo transport through the Golgi apparatus. Mass spectrometry showed that IpaJ cleaved the peptide bond between N-myristoylated glycine-2 and asparagine-3 of human ARF1, thereby providing a new mechanism for host secretory inhibition by a bacterial pathogen. We further demonstrate that IpaJ cleaves an array of N-myristoylated proteins involved in cellular growth, signal transduction, autophagasome maturation and organelle function. Taken together, these findings show a previously unrecognized pathogenic mechanism for the site-specific elimination of N-myristoyl protein modification.


[The long-term results in complicated colorectal cancer (survival for over 3 and 5 years)].
Colorectal cancer survival depends on: stage of primary neoplastic process development, clinical complication pattern and clinical course of the disease, type (radicalism) of the surgical intervention done and histological verification of blastoma. As shown by the results, postoperative lethality in complicated colorectal carcinoma cases amounts to 17.1 per cent, whereas in those undergoing radical surgery for uncomplicated carcinoma it amounts to 6.8 per cent. Patients presenting complicated colorectal carcinoma are admitted to the clinic with diagnosis advanced stage of development of the disease which explains the lower survival rate. The studies performed show that five-year survivorship in patients with complicated colorectal carcinoma amounts to 33.3 per cent, while among those operated for uncomplicated colorectal carcinoma it is 62.7 per cent in the average.


A randomised controlled pilot study: the effectiveness of narrative exposure therapy with adult survivors of the Sichuan earthquake.
Post-Traumatic Stress Disorder (PTSD) is a common psychological reaction after large-scale natural disasters. Given the number of people involved and shortage of resources in any major disaster, brief, pragmatic and easily trainable interventions are needed. The aim of this study is to evaluate the efficacy of Narrative Exposure Therapy (NET) as a short-term treatment for PTSD using Chinese earthquake survivors. A randomized waiting-list control pilot study was conducted between December 2009 and March 2010, at the site of the Sichuan earthquake in Beichuan County, China. Adult participants with newly diagnosed Post Traumatic Stress Disorder (PTSD) were randomly allocated to Narrative Exposure Therapy (NET) or a Waiting-List (WL) condition. The latter received NET treatment after a two-week waiting period. To compare the effectiveness of NET in traumatised earthquake survivors, both groups were assessed on PTSD symptoms, general mental health, anxiety and depression, social support, coping style and posttraumatic change before and after treatment and two months post treatment. Adult participants (n=22) were randomly allocated to receive NET (n=11) or WL (n=11). Twenty two participants (11 in NET group, 11 in WL) were included in the analysis of primary outcomes. Compared with WL, NET showed significant reductions in PTSD symptoms, anxiety and depression, general mental stress and increased posttraumatic growth. The WL group later showed similar improvements after treatment. These changes remained stable for a two-month follow-up. Measures of social support and coping showed no stable effects. NET is effective in treating post-earthquake traumatic symptoms in adult Chinese earthquake survivors. The findings help advance current knowledge in the management of PTSD after natural disasters and inform future research. Larger sample sizes are needed to extend the present findings. Chinese Clinical Trial Registry ChiCTR-TRC-12002473.


Spikes in acute:chronic workload ratio (ACWR) associated with a 5-7 times greater injury rate in English Premier League football players: a comprehensive 3-year study.
We examined the relation between global positioning system (GPS)-derived workloads and injury in English Premier League football players (n=33) over three seasons. Workload and injury data were collected over three consecutive seasons. Cumulative (1-weekly, 2-weekly, 3-weekly and 4-weekly) loads in addition to acute:chronic workload ratios (ACWR) (acute workload (1-week workload)) divided by chronic workload (previous 4-week average acute workload) were classified into discrete ranges by z-scores. Relative risk (RR) for each range was then calculated between injured and non-injured players using specific GPS variables: total distance, low-intensity distance, high-speed running distance, sprint distance, accelerations and decelerations. The greatest non-contact injury risk was when the chronic exposure to decelerations was low (<1731) and the ACWR was >2.0 (RR=6.7). Non-contact injury risk was also 5-6 times higher for accelerations and low-intensity distance when the chronic workloads were categorised as low and the ACWR was >2.0 (RR=5.4-6.6), compared with ACWRs below this. When all chronic workloads were included, an ACWR >2.0 was associated with a significant but lesser injury risk for the same metrics, plus total distance (RR=3.7-3.9). We recommend that practitioners involved in planning training for performance and injury prevention monitor the ACWR, increase chronic exposure to load and avoid spikes that approach or exceed 2.0.


Changes in Liver Antioxidant Status of Offspring Mice Induced by Maternal Fluoride Exposure During Gestation and Lactation.
Excessive fluoride intake for a long time has been demonstrated to provoke hepatic oxidative stress in adults. However, the response to fluoride toxicity of liver in newborns exposed to fluoride during embryonic and suckling stages remains unclear. In this study, female Kunming mice were administrated with 25, 50, and 100 mg/L sodium fluoride (NaF) from prenatal day 0 to day 21 after delivery, and the antioxidative status in the liver of their pups at postnatal day 21 was evaluated. The results showed that compared with the control group, NaF significantly increased malondialdehyde (MDA) level and reduced catalase (CAT) activity, while no statistical difference was observed in activities and mRNA expressions of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR). Notably, with comparison to the controls, the protein level of CAT was significantly reduced in medium- and high-fluoride groups, while its relative mRNA abundance was enhanced which could result from the encouragement of the lowered CAT protein expression. These findings suggested that CAT was more susceptible to low-fluoride exposure in early life.


Modulation of the expression of human LDL-Apo B-100 epitopes by lipids and apolipoproteins.
The purpose of the present study was to determine the immunochemical properties of apolipoprotein (apo) B-100 associated with low density lipoprotein (LDL) in relation to lipid and apolipoprotein composition. LDLs were isolated by sequential ultracentrifugation (1.019 < d < 1.050 g/mL) from two healthy volunteers and 21 dyslipidemic patients to obtain heterogeneous samples of LDL. Lipid (free cholesterol, cholesteryl esters, triglycerides, and phospholipids) and apolipoprotein contents (apo B, apo C-III, apo E) were determined in each LDL sample. Immunoreactivities of apo B were tested in solid-phase competitive-binding radioimmunoassays using seven monoclonal anti-LDL antibodies that reacted with defined epitopes of apo B-100. The relation between lipid and/or protein variables and the immunoreactivity of apo B was evaluated by successive use of Spearman's rank simple correlation, partial correlation, and canonical correlation analyses. The canonical correlation analysis showed that apo B-100 immunoreactivity on LDL is highly dependent on lipid and apolipoprotein composition simultaneously. The results confirmed the influence of surface and core lipids on the expression of the apo B-100 epitopes, independent of their location on the molecule. However, the lipid requirement of LDL strongly influences the expression of epitopes mapped in the LDL receptor-recognition domain. In contrast to apo E, apo C-III does not seem to influence the expression of the apo B-100 epitopes in the LDL range studied.(ABSTRACT TRUNCATED AT 250 WORDS)


Projecting coral reef futures under global warming and ocean acidification.
Many physiological responses in present-day coral reefs to climate change are interpreted as consistent with the imminent disappearance of modern reefs globally because of annual mass bleaching events, carbonate dissolution, and insufficient time for substantial evolutionary responses. Emerging evidence for variability in the coral calcification response to acidification, geographical variation in bleaching susceptibility and recovery, responses to past climate change, and potential rates of adaptation to rapid warming supports an alternative scenario in which reef degradation occurs with greater temporal and spatial heterogeneity than current projections suggest. Reducing uncertainty in projecting coral reef futures requires improved understanding of past responses to rapid climate change; physiological responses to interacting factors, such as temperature, acidification, and nutrients; and the costs and constraints imposed by acclimation and adaptation.


Detection of cryptic chromosomal abnormalities in unexplained mental retardation: a general strategy using hypervariable subtelomeric DNA polymorphisms.
Given the availability of DNA from both parents, unusual segregation of hypervariable DNA polymorphisms (HVPs) in the offspring may be attributable to deletion, unbalanced chromosomal translocation, or uniparental disomy. The telomeric regions of chromosomes are rich in both genes and hypervariable minisatellite sequences and may also be particularly prone to cryptic breakage events. Here I describe and analyze a general approach to the detection of subtelomeric abnormalities and uniparental disomy in patients with unexplained mental retardation. With 29 available polymorphic systems, approximately 50%-70% of these abnormalities could currently be detected. Development of subtelomeric HVPs physically localized with respect to their telomeres should provide a valuable resource in routine diagnostics.


Molecular detection of plant pathogenic bacteria using polymerase chain reaction single-strand conformation polymorphism.
The application of polymerase chain reaction (PCR) technology to molecular diagnostics holds great promise for the early identification of agriculturally important plant pathogens. Ralstonia solanacearum, Xanthomoans axonopodis pv. vesicatoria, and Xanthomonas oryzae pv. oryzae are phytopathogenic bacteria, which can infect vegetables, cause severe yield loss. PCR-single-strand conformation polymorphism (PCR-SSCP) is a simple and powerful technique for identifying sequence changes in amplified DNA. The technique of PCR-SSCP is being exploited so far, only to detect and diagnose human bacterial pathogens in addition to plant pathogenic fungi. Selective media and serology are the commonly used methods for the detection of plant pathogens in infected plant materials. In this study, we developed PCR-SSCP technique to identify phytopathogenic bacteria. The PCR product was denatured and separated on a non-denaturing polyacrylamide gel. SSCP banding patterns were detected by silver staining of nucleic acids. We tested over 56 isolates of R. solanacearum, 44 isolates of X. axonopodis pv. vesicatoria, and 20 isolates of X. oryzae pv. oryzae. With the use of universal primer 16S rRNA, we could discriminate such species at the genus and species levels. Species-specific patterns were obtained for bacteria R. solanacearum, X. axonopodis pv. vesicatoria, and X. oryzae pv. oryzae. The potential use of PCR-SSCP technique for the detection and diagnosis of phytobacterial pathogens is discussed in the present paper.


Smarter medicine: do physicians need political pressure to eliminate useless interventions?
Echoing the "less is more" and "choosing wisely" campaigns in the USA, the "smarter medicine" campaign launched in 2014 by the Swiss Society of General Internal Medicine listed five tests or treatments that are often prescribed in ambulatory general internal medicine, but that may not provide any meaningful benefit and may carry the risk of generating harms and costs. In the United Kingdom, the National Institute for Health and Care Excellence (NICE) supported the National Health Services in identifying "low value" activities that should be stopped. Political pressure and stringent regulatory measures for pharmaceuticals and medical technology triggered major controversy and opposition. NICE efforts now concentrate on editing guidelines based on consensus techniques, which integrate the evidence from systematic reviews with social values and patient preferences. To obtain significant changes and promote the paradigm of reducing unnecessary waste of medical resources, opinion leaders and leading scientific or academic institutions, as well as medical societies, can make a difference, together with consumer associations and the lay press. Politicians can undoubtedly contribute to the success of these strategies, but rather than putting physicians alone under pressure and setting up stringent regulatory measures, they should network with all stakeholders and put emphasis on a broader agenda, the one of improving healthcare quality and efficiency.


Combined treatment with laser sintering and zirconium: a case report of dentinogenesis imperfecta.
Osteogenesis imperfecta (OI) is a heterogeneous disorder of connective tissue that manifests mainly as skeletal deformity and bone fragility. Dentinogenesis imperfecta (DI) is sometimes an accompanying symptom of OI. The treatment protocol of these patients varies according to the clinical appearance. The case report here describes complete mouth rehabilitation of an 18-year-old male patient with OI and DI using direct metal laser sintering (DMLS) technique of metal-ceramic restorations and zirconium all-ceramic crowns. DMLS is an additive metal fabrication technology that is simpler, more precise, and healthier than conventional manufacturing and can be remarkably cost effective. Moreover, the technique affords highly accurate production of fixed partial dentures with ideal marginal fit and excellent mechanical properties. The patient was treated using a multidisciplinary strategy that focused on controlling caries, protecting teeth from further wear, obtaining an appropriate vertical dimension, and providing soft tissue support to return the facial profile to a normal appearance using new technology in the field of prosthetics.


Noninvasive (1)H and (23)Na nuclear magnetic resonance imaging of ancient Egyptian human mummified tissue.
Historic mummies are a unique example of the human desire for immortality. Therefore, it is not surprising that modern diagnostic imaging has been widely applied to study them. Yet, magnetic resonance imaging (MRI) of such old remains has never been successfully achieved in a noninvasive way without rehydration. Furthermore, the impact of artificial mummification as done in ancient Egypt by natron (a blend of NaCl, Na(2)CO(3), NaHCO(3) and NaP(2)SO(4)) on human tissue with a particular focus on the sodium spatial distribution has never been addressed. Here, we show for the very first time completely noninvasive (1)H and (23)Na imaging of an ancient Egyptian mummified finger by nuclear magnetic resonance (NMR). Protons could be visualized by NMR only in the tissue close to surface and sodium primarily in the bone, while computer tomography images both, soft tissue and bone but does not distinguish between different chemical elements. The selective enrichment of sodium in the bone may by due to postmortem incorporation of (23)Na into the tissue by natron-based mummification because our reference measurement of a historical finger not subjected to artificial mummification showed no sodium signal at all. Our results demonstrate not only the general feasibility of nonclinical MRI to visualize historic dry human tissues but also shows the specific (1)H and (23)Na spatial distributions in such mummy tissue, which is particularly interesting for archeology and may open up a new application for MRI.


Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial.
Outcomes for patients with recurrent glioblastoma multiforme (GBM) are poor and may be improved by immunotherapy. We investigated the safety and efficacy of an autologous heat-shock protein peptide complex-96 (HSPPC-96) vaccine for patients with recurrent GBM. In this open-label, single-arm, phase II study, adult patients with surgically resectable recurrent GBM were given vaccine after gross total resection. The primary endpoint was overall survival at 6 months. Secondary endpoints included overall survival, progression-free survival, safety, and immune profiling. Outcome analyses were performed in the intention-to-treat and efficacy populations. Between October 3, 2007 and October 24, 2011, 41 patients underwent gross total resection of recurrent GBM and received a median of 6 doses of HSPPC-96 vaccine. Following treatment, 90.2% of patients were alive at 6 months (95% confidence interval [CI]: 75.9-96.8) and 29.3% were alive at 12 months (95% CI: 16.6-45.7). Median overall survival was 42.6 weeks (95% CI: 34.7-50.5). Twenty-seven (66%) patients were lymphopenic prior to therapy, and patients with lymphocyte counts below the cohort median demonstrated decreased overall survival (hazard ratio: 4.0; 95% CI: 1.4-11.8; P = .012). There were no treatment-related deaths. There were 37 serious (grades 3-5) adverse events reported, with 17 attributable to surgical resection and a single grade 3 constitutional event related to the vaccine. The HSPPC-96 vaccine is safe and warrants further study of efficacy for the treatment of recurrent GBM. Significant pretreatment lymphopenia may impact the outcomes of immunotherapy and deserves additional investigation.


The Global Burden of Disease Study and the Preventable Burden of NCD.
Noncommunicable diseases (NCD) now account for more than one-half of the global burden of disease. Cardiovascular diseases account for about one-half of NCD deaths, and the majority of cardiovascular disease deaths occur in low- and middle-income countries. The GBD (Global Burden of Disease) study measures and benchmarks health loss from death or disability from more than 300 diseases in over 100 countries. According to GBD analyses, the rise of NCD is in part due to increased life expectancy due to reduced premature mortality from communicable, child, and maternal illnesses, but preventable risk factors also contribute and present targets for NCD control efforts. In addition to traditional NCD risk factors, like tobacco smoking, high blood pressure, and unhealthful diet, nontraditional risk factors like air pollution and unhealthful alcohol consumption also play a role. The GBD study continues to grow by gathering more data from country partners than ever before, and by measuring health at the national and subnational levels and in smaller time increments. The GBD study will continue to provide the data to set priorities for and measure progress in the global effort to control the rising burden of NCD.


Erosive Potential of 1% Phytic Acid on Radicular Dentine at Different Time Intervals.
The objective of this in-vitro study was to compare the erosive potential and smear layer removal ability of 1% Phytic acid (IP6) and 17% Ethylenediaminetetaacetic acid (EDTA). Canal preparation of 225 single rooted extracted human teeth was performed with Protaper NiTi rotary instruments. Teeth were divided into three groups according to the final irrigation protocol. Group 1: Saline irrigation (n=75), Group 2: 17% EDTA (n=75), Group 3: 1% Phytic Acid (n=75). Roots were splitted and observed under Scanning Electron Microscope (SEM) for erosion and smear layer removal. Mean differences between the groups for smear layer removal and erosion were assessed using the Kruskal Wallis and Mann Whitney U test. (P≤0.05) Friedman and Willcoxon Signed Rank tests were used to make comparisons within the groups. Group 3 was significantly less erosive than Group 2 at all root portions (P<0.001). With regards to smear layer removal, group 2 (EDTA) removed more smear layer compared to group 3 (Phytic acid) at all root portions (P<0.001). Both 17% EDTA and 1% IP6 removed significantly less smear layer in the apical root portion. Intra group comparisons revealed no significant differences at any root level. There was a time dependent increase in erosion and smear layer removal in Group 2, with severe erosion at 5 minutes time interval. In Group 3, however, there was moderate erosion and smear removal at 3 and 5 minutes interval. IP6 at the concentration of 1% and pH 3 was less erosive than 17% EDTA. It exhibited moderate smear layer removal ability.


Long-term results of tumor necrosis factor alpha- and melphalan-based isolated limb perfusion in locally advanced extremity soft tissue sarcomas.
Because there is no survival benefit of amputation for extremity soft tissue sarcomas (STSs), limb-sparing surgery has become the gold standard. Tumor size reduction by induction therapy to render nonresectable tumors resectable or facilitate function-preserving surgery can be achieved by tumor necrosis factor α (TNF) -based and melphalan-based isolated limb perfusion (TM-ILP). This study reports the long-term results of 231 TM-ILPs for locally advanced extremity STS. We analyzed 231 TM-ILPs in 208 consecutive patients (1991 to 2005), who were all candidates for functional or anatomic amputation for locally advanced extremity STS. All patients had a potential follow-up of up to 5 years. TM-ILP was performed under mild hyperthermic conditions with 1 to 4 mg of TNF and 10 to 13 mg/L of limb-volume melphalan. Almost all patients (85%) had intermediate- or high-grade tumors. The overall response rate (ORR) was 71% (complete response, 18%; partial response, 53%). Multifocal sarcomas had a significantly better ORR of 83% (P = .008). The local recurrence rate was 30% (n = 70); local recurrence rates were highest for multifocal tumors (54%; P = .001) and after previous radiotherapy (54%; P < .001). Five-year overall survival rate was 42%. Survival was poorest in patients with large tumors (P = .01) and with leiomyosarcomas (P < .001). Limb salvage rate was 81%. We demonstrated that TM-ILP results in a limb salvage rate of 81% in patients with locally advanced extremity STS who would otherwise have undergone amputation. Whenever an amputation is deemed necessary to obtain local control of an extremity STS, TM-ILP should be considered.


Suppression by enhanced RpoE activity of the temperature-sensitive phenotype of a degP ssrA double mutant in Escherichia coli.
SsrA is a small RNA playing a crucial role in trans-translation, which leads to rescue of stalled ribosomes on or at the end of mRNA and addition of the degradation tag to a growing polypeptide. The lack of SsrA has been shown to enhance the temperature-sensitive (ts) phenotype of an E. coli strain defective in the degP gene, which encodes one of the periplasmic proteases. This severe ts phenotype was relieved only partially by an SsrADD variant, which can lead to ribosome rescue but adds a protease-resistant tag instead of the degradation tag, suggesting that accumulation of polypeptides programmed by truncated mRNAs is responsible for growth defect of the ssrA degP mutant. Expression of an S210A-mutant DegP protein, which lacks the protease activity but retains the chaperone activity, could relieve the ts phenotype of the double mutant, suggesting that the chaperone activity but not the protease activity of DegP is required for growth of the ssrA-deficient cells at high temperature. Overexpression of the rpoE gene, which encodes sigmaE responsible for the expression of factors involved in extracellular stress response, also suppressed the ts phenotype of the ssrA degP mutant. This suggests that the stress-responsing pathway(s) may be involved in the enhancement of ts phenotype of degP mutant in the absence of SsrA.


Chitosan/hydroxyapatite composite bone tissue engineering scaffolds with dual and decoupled therapeutic ion delivery: copper and strontium.
Therapeutic metal ions are a family of metal ions characterized by specific biological properties that could be exploited in bone tissue engineering, avoiding the use of expensive and potentially problematic growth factors and other sensitive biomolecules. In this work, we report the successful preparation and characterization of two material platforms containing therapeutic ions: a copper(ii)-chitosan derivative and a strontium-substituted hydroxyapatite. These biomaterials showed ideal ion release profiles, offering burst release of an antibacterial agent together with a more sustained release of strontium in order to achieve long-term osteogenesis. We combined copper(ii)-chitosan and strontium-hydroxyapatite into freeze-dried composite scaffolds. These scaffolds were characterized in terms of morphology, mechanical properties and bioactivity, defined here as the ability to trigger the deposition of novel calcium phosphate in contact with biological fluids. In addition, a preliminary biological characterization using cell line osteoblasts was performed. Our results highlighted that the combination of chitosan and hydroxyapatite in conjunction with copper and strontium has great potential in the design of novel scaffolds. Chitosan/HA composites can be an ideal technology for the development of tissue engineering scaffolds that deliver a complex arrays of therapeutic ions in both components of the composite, leading to tailored biological effects, from antibacterial activity, to osteogenesis and angiogenesis.


Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators.
The human thyroid hormone receptor-associated protein (TRAP) complex, an earlier described coactivator for nuclear receptors, and an SRB- and MED-containing cofactor complex (SMCC) that mediates activation by Gal4-p53 are shown to be virtually the same with respect to specific polypeptide subunits, coactivator functions, and mechanisms of action (activator interactions). In parallel with ligand-dependent interactions of nuclear receptors with the TRAP220 subunit, p53 and VP16 activation domains interact directly with a newly cloned TRAP80 subunit. These results indicate novel pathways for the function of nuclear receptors and other activators (p53 and VP16) through a common coactivator complex that is likely to target RNA polymerase II. Identification of the TRAP230 subunit as a previously predicted gene product also suggests a coactivator-related transcription defect in certain disease states.


Risk factors for left ventricular dysfunction in adulthood: role of low birth weight.
This study aimed to determine the relationship of low birth weight (LBW) with adult cardiac structure and function and investigate potential causal pathways. A population-based sample of 925 Australians (41.3% male) were followed from childhood (aged 7-15 years) to young adulthood (aged 26-36 years) and mid-adulthood (aged 36-50 years). Left ventricular (LV) global longitudinal strain (GLS, %), LV mass index (LVMi, g/m2.7 ), LV filling pressure (E/e'), and left atrial volume index (g/m2 ) were measured by transthoracic echocardiography in mid-adulthood. Birth weight category was self-reported in young adulthood and classified as low (≤5 lb or ≤2270 g), normal (5-8 lb or 2271-3630 g), and high (>8 lb or >3630 g). Of the 925 participants, 7.5% (n = 69) were classified as LBW. Compared with participants with normal birth weight, those with LBW had 2.01-fold (95% confidence interval: 1.19, 3.41, P = 0.009) higher risks of impaired GLS (GLS > -18%) and 2.63-fold (95% confidence interval: 0.89, 7.81, P = 0.08) higher risks of LV hypertrophy (LVMi > 48 g/m2.7 in men or >44 g/m2.7 in women) in adulthood, independent of age, sex, and any socio-economic factors. Participants with LBW significantly increased body fat from childhood to adulthood relative to their peers and had greater levels of triglycerides, fasting glucose, and arterial stiffness in adulthood. These risk factors were the strongest mediators and explained 54% of the LBW effect size on adult GLS and 33% of the LBW effect size on LVMi. The remaining of these associations was independent of any of the measured risk factors. Low birth weight was associated with impaired cardiac structure and function in mid-adulthood. This association was only partially explained by known risk factors.


Microfluidic chip-based detection and intraspecies strain discrimination of Salmonella serovars derived from whole blood of septic mice.
Salmonella is a zoonotic pathogen that poses a considerable public health and economic burden in the United States and worldwide. Resultant human diseases range from enterocolitis to bacteremia to sepsis and are acutely dependent on the particular serovar of Salmonella enterica subsp. enterica, which comprises over 99% of human-pathogenic S. enterica isolates. Point-of-care methods for detection and strain discrimination of Salmonella serovars would thus have considerable benefit to medical, veterinary, and field applications that safeguard public health and reduce industry-associated losses. Here we describe a single, disposable microfluidic chip that supports isothermal amplification and sequence-specific detection and discrimination of Salmonella serovars derived from whole blood of septic mice. The integrated microfluidic electrochemical DNA (IMED) chip consists of an amplification chamber that supports loop-mediated isothermal amplification (LAMP), a rapid, single-temperature amplification method as an alternative to PCR that offers advantages in terms of sensitivity, reaction speed, and amplicon yield. The amplification chamber is connected via a microchannel to a detection chamber containing a reagentless, multiplexed (here biplex) sensing array for sequence-specific electrochemical DNA (E-DNA) detection of the LAMP products. Validation of the IMED device was assessed by the detection and discrimination of S. enterica subsp. enterica serovars Typhimurium and Choleraesuis, the causative agents of enterocolitis and sepsis in humans, respectively. IMED chips conferred rapid (under 2 h) detection and discrimination of these strains at clinically relevant levels (<1,000 CFU/ml) from whole, unprocessed blood collected from septic animals. The IMED-based chip assay shows considerable promise as a rapid, inexpensive, and portable point-of-care diagnostic platform for the detection and strain-specific discrimination of microbial pathogens.


Nuclear localization and functional characteristics of voltage-gated potassium channel Kv1.3.
It is widely known that ion channels are expressed in the plasma membrane. However, a few studies have suggested that several ion channels including voltage-gated K(+) (Kv) channels also exist in intracellular organelles where they are involved in the biochemical events associated with cell signaling. In the present study, Western blot analysis using fractionated protein clearly indicates that Kv1.3 channels are expressed in the nuclei of MCF7, A549, and SNU-484 cancer cells and human brain tissues. In addition, Kv1.3 is located in the plasma membrane and the nucleus of Jurkat T cells. Nuclear membrane hyperpolarization after treatment with margatoxin (MgTX), a specific blocker of Kv1.3 channels, provides evidence for functional channels at the nuclear membrane of A549 cells. MgTX-induced hyperpolarization is abolished in the nuclei of Kv1.3 silenced cells, and the effects of MgTX are dependent on the magnitude of the K(+) gradient across the nuclear membrane. Selective Kv1.3 blockers induce the phosphorylation of cAMP response element-binding protein (CREB) and c-Fos activation. Moreover, Kv1.3 is shown to form a complex with the upstream binding factor 1 in the nucleus. Chromatin immunoprecipitation assay reveals that Sp1 transcription factor is directly bound to the promoter region of the Kv1.3 gene, and the Sp1 regulates Kv1.3 expression in the nucleus of A549 cells. These results demonstrate that Kv1.3 channels are primarily localized in the nucleus of several types of cancer cells and human brain tissues where they are capable of regulating nuclear membrane potential and activation of transcription factors, such as phosphorylated CREB and c-Fos.


Progressive nonfluent aphasia and its characteristic motor speech deficits.
Progressive nonfluent aphasia (PNFA) is a clinical syndrome characterized by motor speech impairment and agrammatism, with relative sparing of single word comprehension and semantic memory. PNFA has been associated with the characteristic pattern of left anterior insular and posterior frontal atrophy, including the motor and premotor regions and Broca's area. Postmortem histopathologic evidence has shown that PNFA is usually associated with tau pathology, although focal Alzheimer disease pathology and tau-negative, ubiquitin-TDP-43 inclusions also have been reported in association with this clinical syndrome. We performed a detailed analysis of motor speech errors in 18 patients with PNFA and investigated their neural correlates using voxel-based morphometry on magnetic resonance imaging scans. Seven patients demonstrated only apraxia of speech (AOS) errors, whereas 11 showed AOS along with dysarthria. Slow rate of speech, effortful articulation with groping, and consonant distortions were the most common AOS errors. Hypernasality was the most represented dysarthric feature and dysarthria was most often classified as spastic, hypokinetic, or mixed spastic-hypokinetic. Neuroimaging results demonstrated that patients with AOS-only and AOS plus dysarthria showed atrophy in the left posterior frontal, anterior insular, and basal ganglia regions when compared with controls. Patients with AOS plus dysarthria showed greater damage than patients with AOS-only in the left face portion of primary motor cortex and left caudate. PNFA is a distinct frontotemporal lobar degeneration clinical syndrome associated with characteristic clinical, neuroimaging, and pathologic features. The clinical features are driven by the severity of left frontal and caudate damage.


Effect of Transition Metal Cations on Stability Enhancement for Molybdate-Based Hybrid Supercapacitor.
The race for better electrochemical energy storage systems has prompted examination of the stability in the molybdate framework (MMoO4; M = Mn, Co, or Ni) based on a range of transition metal cations from both computational and experimental approaches. Molybdate materials synthesized with controlled nanoscale morphologies (such as nanorods, agglomerated nanostructures, and nanoneedles for Mn, Co, and Ni elements, respectively) have been used as a cathode in hybrid energy storage systems. The computational and experimental data confirms that the MnMoO4 crystallized in β-form with α-MnMoO4 type whereas Co and Ni cations crystallized in α-form with α-CoMoO4 type structure. Among the various transition metal cations studied, hybrid device comprising NiMoO4 vs activated carbon exhibited excellent electrochemical performance having the specific capacitance 82 F g-1 at a current density of 0.1 A g-1 but the cycling stability needed to be significantly improved. The specific capacitance of the NiMoO4 electrode material is shown to be directly related to the surface area of the electrode/electrolyte interface, but the CoMoO4 and MnMoO4 favored a bulk formation that could be suitable for structural stability. The useful insights from the electronic structure analysis and effective mass have been provided to demonstrate the role of cations in the molybdate structure and its influence in electrochemical energy storage. With improved cycling stability, NiMoO4 can be suitable for renewable energy storage. Overall, this study will enable the development of next generation molybdate materials with multiple cation substitution resulting in better cycling stability and higher specific capacitance.


Current Status of MRI and PET in the NCCN Guidelines for Prostate Cancer.
Prostate cancer (PCa) represents a significant source of morbidity and mortality for men in the United States, with approximately 1 in 9 being diagnosed with PCa in their lifetime. The role of imaging in the evaluation of men with PCa has evolved and currently plays a central role in diagnosis, treatment planning, and evaluation of recurrence. Appropriate use of multiparametric MRI (mpMRI) and MRI-guided transrectal ultrasound (MR-TRUS) biopsy increases the detection of clinically significant PCa while decreasing the detection of clinically insignificant PCa. This process may help patients with clinically insignificant PCa avoid the adverse effects of unnecessary therapy. In the setting of a known PCa, patients with low-grade disease can be observed using active surveillance, which often includes a combination of prostate-specific antigen (PSA) testing, serial mpMRI, and, if indicated, follow-up systematic and targeted TRUS-guided tissue sampling. mpMRI can provide important information in the posttreatment setting, but PET/CT is creating a paradigm shift in imaging standards for patients with locally recurrent and metastatic PCa. This article examines the strengths and limitations of mpMRI for initial PCa diagnosis, active surveillance, recurrent disease evaluation, and image-guided biopsies, and the use of PET/CT imaging in men with recurrent PCa. The goal of this review is to provide a rational basis for current NCCN Clinical Practice Guidelines in Oncology for PCa as they pertain to the use of these advanced imaging modalities.


Patterns of alcohol consumption and alcohol-impaired driving in the United States.
Alcohol-related motor vehicle crashes kill approximately 17,000 Americans annually and were associated with more than $51 billion in total costs in 2000. Relatively little is known about the drinking patterns of alcohol-impaired (AI) drivers in the United States. 2006 Behavioral Risk Factor Surveillance System (BRFSS) was analyzed for alcohol consumption and self-reported AI driving among U.S. adults aged > or =18 years for all states. Alcohol consumption was divided into 4 categories: binge/heavy, binge/nonheavy, nonbinge/heavy, and nonbinge/nonheavy. Binge drinking was defined as > or =5 drinks for men or > or =4 drinks for women on one or more occasions in the past month, and heavy drinking was defined as average daily consumption of >2 drinks/day (men) or >1 drink/day (women). The prevalence of AI driving was examined by drinking pattern and by demographic characteristics. Logistic regression analysis was used to assess the association between drinking patterns and AI driving. Five percent of drinkers were engaged in AI driving during the past 30 days. Overall, 84% of AI drivers were binge drinkers and 88% of AI driving episodes involved binge drinkers. By drinking category, binge/nonheavy drinkers accounted for the largest percentage of AI drivers (49.4%), while binge/heavy drinkers accounted for the most episodes of AI driving (51.3%). The adjusted odds of AI driving were 20.1 (95% CI: 16.7, 24.3) for binge/heavy, 8.2 (6.9, 9.7) for binge/nonheavy, and 3.9 (2.4, 6.3) for nonbinge/heavy drinkers, respectively. There is a strong association between binge drinking and AI driving. Most AI drivers and almost half of all AI driving episodes involve persons who are not heavy drinkers (based on average daily consumption). Implementing effective interventions to prevent binge drinking could substantially reduce AI driving.


Relationships in couples treated with sperm donation - a national prospective follow-up study.
Long-term follow-up on relationship quality in couples who use sperm donation is scarce. Therefore, this study aimed to analyse changes over time in satisfaction with relationship in heterosexual couples who were scheduled for treatment with sperm donation and IVF couples treated with their own gametes and to compare the two groups undergoing different treatment for infertility. A prospective follow-up study in which data were collected twice on two groups; couples receiving sperm donation and IVF couples using their own gametes. The ENRICH instrument was used to gain information about the individuals' subjective experience of their relationship at the time of acceptance for treatment and again 2-5 years later. At the time of acceptance for treatment the men and women in the two groups assessed their relationships as being very solid on all dimensions and that there were no differences between the two groups. At the second assessment there was a decline in the satisfaction scores on the dimensions "Children and parenting" and "Egalitarian", while an increase in scores was observed on "Conception of life" and "Conflict resolution" both for men and woman and also for the two groups. For the couples that had a successful treatment and gave birth to a child/children there was a decrease in satisfaction of the relation in the sperm donation group as well as in the group of couples having IVF with own gametes. In conclusion, the overall quality of relationship is stable in couples receiving donated sperm and does not differ from couples undergoing IVF-treatment with own gametes.


Behavioral thermoregulation is highly repeatable and unaffected by digestive status in Agama atra.
The precision and the extent of behavioral thermoregulation are likely to provide fitness benefits to ectotherms. Yet the factors driving variation in selected or preferred body temperature (Tset ) and its usefulness as a proxy for optimal physiological temperature (Topt ) are still debated. Although Tset is often conserved among closely related species, substantial variation at the individual, population and species level has also been reported. However, the repeatability (calculated as the intra-class correlation coefficient) of Tset is generally low. One factor that influences Tset is feeding status, with fed reptiles typically showing higher Tset , a process thought to aid meal digestion. Here, using experiments simulating realistic feeding and fasting regimes in Agama atra, a heliothermic lizard from southern Africa, we test if Tset and its repeatability under these 2 states significantly differ. Daily Tset ranged from 33.7 to 38.4 °C, with a mean (± SE) of 36.7 ± 0.1 °C for fed and 36.6 ± 0.1 °C for unfed individuals. Comparisons of repeatability showed that females tend to be more consistent in the selection of body temperature than males, but not significantly so regardless of feeding status. We report some of the highest repeatability estimates of Tset to date (full range: 0.229-0.642), and that the weak positive effects of feeding status on Tset did not increase its repeatability. In conclusion, one of the major prerequisites for natural selection, consistent among-individual variation, is present, making the adaptive significance of Tset considerably more plausible.


Lack of clinically significant gross structural abnormalities in MRIs of older patients with schizophrenia and related psychoses.
The authors examined the reports of MRI brain studies of 69 patients with DSM-III-R-diagnosed psychotic disorders (30 early-onset and 24 late-onset schizophrenia patients and 15 with other psychoses) and 41 normal comparison subjects. Participants' ages ranged from 45 to 87 years. A qualitative rating scheme determined type and severity of clinically detectable abnormalities, including volume loss, infarcts, lacunae, and white matter hyperintensities. In this clinically well-characterized sample, the vast majority of the MRIs were within normal limits. There were no significant differences between psychosis patients and normal comparison subjects or between early-onset and late-onset schizophrenia patients in frequency, type, or severity of gross structural abnormalities. The results indicate that late-onset schizophrenia and related disorders can exist without clinically significant gross structural abnormalities in the brain.


The association between neonatal vitamin D status and risk of schizophrenia.
Clues from the epidemiology of schizophrenia, such as the increased risk in those born in winter/spring, have led to the hypothesis that prenatal vitamin D deficiency may increase the risk of later schizophrenia. We wish to explore this hypothesis in a large Danish case-control study (n = 2602). The concentration of 25 hydroxyvitamin D (25OHD) was assessed from neonatal dried blood samples. Incidence rate ratios (IRR) were calculated when examined for quintiles of 25OHD concentration. In addition, we examined statistical models that combined 25OHD concentration and the schizophrenia polygenic risk score (PRS) in a sample that combined the new sample with a previous study (total n = 3464; samples assayed and genotyped between 2008-2013). Compared to the reference (fourth) quintile, those in the lowest quintile (<20.4 nmol/L) had a significantly increased risk of schizophrenia (IRR = 1.44, 95%CI: 1.12-1.85). None of the other quintile comparisons were significantly different. There was no significant interaction between 25OHD and the PRS. Neonatal vitamin D deficiency was associated with an increased risk for schizophrenia in later life. These findings could have important public health implications related to the primary prevention of schizophrenia.


Duty, Honor, Country, Disparity: Race/Ethnic Differences in Health and Disability among Male Veterans.
Given their unique occupational hazards and sizable population, military veterans are an important population for the study of health. Yet veterans are by no means homogeneous, and there are unanswered questions regarding the extent of, and explanations for, racial and ethnic differences in veterans' health. Using the 2010 National Survey of Veterans, we first documented race/ethnic differences in self-rated health and limitations in Activities of Daily Living among male veterans aged 30-84. Second, we examined potential explanations for the disparities, including socioeconomic and behavioral differences, as well as differences in specific military experiences. We found that Black, Hispanic, and other/multiple race veterans reported much worse health than White veterans. Using progressively adjusted regression models, we uncovered that the poorer self-rated health and higher levels of activity limitations among minority veterans compared to Whites was partially explained by differences in their socioeconomic status and by their military experiences. Minority veterans are a vulnerable population for poor health; future research and policy efforts should attempt to better understand and ameliorate their health disadvantages relative to White veterans.


A double blind randomized controlled trial of a probiotic combination in 100 patients with irritable bowel syndrome.
The purpose of this study was to evaluate the effects of a probiotic combination on symptoms in patients with irritable bowel syndrome (IBS). We investigated the efficiency of a probiotic dietary supplement, containing four strains of lactic acid bacteria, on symptoms of IBS. One hundred and sixteen patients with IBS fulfilling the Rome II criteria were randomized in a parallel group, double-blind study to receive a placebo or a probiotic combination (1 x 10(10) cfu once daily) for four weeks. The symptoms that were monitored weekly included discomfort, abdominal pain, and stool frequency and quality. Quality of life was assessed before and at the end of the treatment using the SF36 and FDD-quality-of-life questionnaires. One hundred subjects completed the study (48 probiotic combination, 52 placebo). The probiotic combination was not superior to the placebo in relieving symptoms of IBS (42.6 versus 42.3% improvement). However, the decrease of abdominal pain between the first and the fourth week of treatment was significantly higher in probiotic treated patients (-41.9 versus -24.2%, P=0.048). Interesting findings from the IBS sub-groups were also observed such as a lower pain score at end point in patients with alternating bowel habits (P=0.023) and an increase of stool frequency in the constipated sub-group from the first week of probiotic treatment (P=0.043). The probiotic combination was not significantly superior to the placebo in relieving symptoms of IBS. Despite the apparent high placebo response, interesting findings from IBS sub-groups were observed in the field of abdominal pain and stool frequency.


Toxicity of sediment pore water in Puget Sound (Washington, USA): a review of spatial status and temporal trends.
Data from toxicity tests of the pore water extracted from Puget Sound sediments were compiled from surveys conducted from 1997 to 2009. Tests were performed on 664 samples collected throughout all of the eight monitoring regions in the Sound, an area encompassing 2,294.1 km(2). Tests were performed with the gametes of the Pacific purple sea urchin, Strongylocentrotus purpuratus, to measure percent fertilization success as an indicator of relative sediment quality. Data were evaluated to determine the incidence, degree of response, geographic patterns, spatial extent, and temporal changes in toxicity. This is the first survey of this kind and magnitude in Puget Sound. In the initial round of surveys of the eight regions, 40 of 381 samples were toxic for an incidence of 10.5 %. Stations classified as toxic represented an estimated total of 107.1 km(2), equivalent to 4.7 % of the total area. Percent sea urchin fertilization ranged from >100 % of the nontoxic, negative controls to 0 %. Toxicity was most prevalent and pervasive in the industrialized harbors and lowest in the deep basins. Conditions were intermediate in deep-water passages, urban bays, and rural bays. A second round of testing in four regions and three selected urban bays was completed 5-10 years following the first round. The incidence and spatial extent of toxicity decreased in two of the regions and two of the bays and increased in the other two regions and the third bay; however, only the latter change was statistically significant. Both the incidence and spatial extent of toxicity were lower in the Sound than in most other US estuaries and marine bays.


Biocomputing based on particle disassembly.
Nanoparticles with biocomputing capabilities could potentially be used to create sophisticated robotic devices with a variety of biomedical applications, including intelligent sensors and theranostic agents. DNA/RNA-based computing techniques have already been developed that can offer a complete set of Boolean logic functions and have been used, for example, to analyse cells and deliver molecular payloads. However, the computing potential of particle-based systems remains relatively unexplored. Here, we show that almost any type of nanoparticle or microparticle can be transformed into autonomous biocomputing structures that are capable of implementing a functionally complete set of Boolean logic gates (YES, NOT, AND and OR) and binding to a target as result of a computation. The logic-gating functionality is incorporated into self-assembled particle/biomolecule interfaces (demonstrated here with proteins) and the logic gating is achieved through input-induced disassembly of the structures. To illustrate the capabilities of the approach, we show that the structures can be used for logic-gated cell targeting and advanced immunoassays.


Facts and fictions: Characters seeking abortion on American television, 2005-2014.
We aim to describe how women who seek abortions are portrayed on television, recognizing that onscreen fictional stories can shape the public's beliefs. Drawing on a comprehensive online search, we identified all fictional representations of abortion decision making on U.S. television from 2005 through 2014. Characters who considered abortion in these plotlines were quantitatively content coded for their demographic details and reasons for abortion, with 95% intercoder reliability. Seventy-eight plotlines were identified, including 40 plotlines (51%) wherein a character obtained an abortion. Characters who considered abortion were mostly white, young, in committed relationships and not parenting. Comparing all abortion-considering characters to the subset of abortion-obtaining characters, the higher rates of abortion were found for characters who were white, of lower socioeconomic status and not in committed relationships. Compared to statistics on real women, characters who obtained abortions were disproportionately white, young, wealthy and not parenting. Compared to reports on real women's reasons for abortion, immaturity or interference with future opportunities was overrepresented; financial hardship or pregnancy mistiming was underrepresented. Taken in aggregate, televised abortion stories misrepresent the demographics of women obtaining abortion and their reasons for doing so, overrepresenting younger white women and underrepresenting women of color, poor women and mothers. Overrepresented reasons were more often self-focused rather than other-focused, contributing to a perception that abortion is a want rather than a need. Findings hint at the politics of onscreen abortions, suggesting that it is easier to portray with peripheral characters and among some demographics (e.g., teens). Onscreen representations may influence public understandings, contributing to the production of abortion stigma and judgments about appropriate restrictions on abortion care. Understanding the particular shape of inaccuracies around abortion portrayals can enable advocates and healthcare practitioners to identify and respond to popular misperceptions.


Modeling host genetic regulation of influenza pathogenesis in the collaborative cross.
Genetic variation contributes to host responses and outcomes following infection by influenza A virus or other viral infections. Yet narrow windows of disease symptoms and confounding environmental factors have made it difficult to identify polymorphic genes that contribute to differential disease outcomes in human populations. Therefore, to control for these confounding environmental variables in a system that models the levels of genetic diversity found in outbred populations such as humans, we used incipient lines of the highly genetically diverse Collaborative Cross (CC) recombinant inbred (RI) panel (the pre-CC population) to study how genetic variation impacts influenza associated disease across a genetically diverse population. A wide range of variation in influenza disease related phenotypes including virus replication, virus-induced inflammation, and weight loss was observed. Many of the disease associated phenotypes were correlated, with viral replication and virus-induced inflammation being predictors of virus-induced weight loss. Despite these correlations, pre-CC mice with unique and novel disease phenotype combinations were observed. We also identified sets of transcripts (modules) that were correlated with aspects of disease. In order to identify how host genetic polymorphisms contribute to the observed variation in disease, we conducted quantitative trait loci (QTL) mapping. We identified several QTL contributing to specific aspects of the host response including virus-induced weight loss, titer, pulmonary edema, neutrophil recruitment to the airways, and transcriptional expression. Existing whole-genome sequence data was applied to identify high priority candidate genes within QTL regions. A key host response QTL was located at the site of the known anti-influenza Mx1 gene. We sequenced the coding regions of Mx1 in the eight CC founder strains, and identified a novel Mx1 allele that showed reduced ability to inhibit viral replication, while maintaining protection from weight loss.


Cancer risk of anti-TNF-α at recommended doses in adult rheumatoid arthritis: a meta-analysis with intention to treat and per protocol analyses.
The risk of malignancies on TNF-α antagonists is controversial. The aim of this survey was to assess cancer risk on TNF-α antagonists in adult rheumatoid arthritis patients, including the five marketed drugs (infliximab, etanercept, adalimumab, golimumab and certolizumab) used in line with the New Drug Application. Furthermore, the relative interest of modified intention to treat or per protocol analyses to assess such sparse events remains unknown. Data sources were MEDLINE, CENTRAL, ISI Web of Science, ACR and EULAR meeting abstracts, scientific evaluation of the drugs leading to their marketing approval, and clinicaltrials.gov, until 31 December 2012.We selected double-blind randomized controlled trials in adult rheumatoid arthritis patients, including at least one treatment arm in line with New Drug Application. We performed random effect meta-analysis, with modified intention to treat and per protocol analyses. Thirty-three trials were included. There was no excess risk of malignancies on anti-TNF-α administered in line with New Drug Application in the per protocol model (OR, 0.93 95%CI[0.59-1.44]), as well as in the modified intention to treat model (OR, 1.27 95%CI[0.82-1.98]). There was a non-significant tendency for an excess non-melanoma skin cancer risk in both models (respectively, 1.37 [0.71-2.66] and 1.90 [0.98-3.67]). With fixed effect Peto model restricting to trials during at least 52 weeks, the overall cancer risk was respectively 1.60 [0.97-2.64] and 1.22 [0.72-2.08]. Whatever the model, modified intention to treat analysis led to higher estimations than per protocol analysis. The later may underestimate the treatment effect when assessing very sparse events and when many patients dropped out in placebo arms. In metaregression, there was no differential risk among the five drugs. This study did not find any evidence for an excess cancer risk on TNF-α antagonists in adult rheumatoid arthritis patients, but an excess cancer risk after several years of exposure cannot be ruled out. Both modified intention to treat and per protocol analyses should be presented in such safety analyses.