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Rapid identification of potentially life-threatening blood stream infections (BSI) improves clinical outcomes, yet conventional blood culture (BC) identification methods require ~24–72 hours of liquid culture, plus 24–48 hours to generate single colonies on solid media suitable for identification by mass spectrometry (MS). Newer rapid centrifugation techniques, such as the Bruker MBT-Sepsityper® IVD, replace culturing on solid media and expedite the diagnosis of BCs but frequently demonstrate reduced sensitivity for identifying clinically significant Gram-positive bacterial or fungal infections. This study introduces a protocol that utilises the broad-range binding properties of an engineered version of mannose-binding lectin linked to the Fc portion of immunoglobulin (FcMBL) to capture and enrich pathogens combined with matrix-assisted laser desorption-ionisation time-of-flight (MALDI-TOF) MS for enhanced infection identification in BCs. The FcMBL method identified 94.1% (64 of 68) of clinical BCs processed, with a high sensitivity for both Gram-negative and Gram-positive bacteria (94.7 and 93.2%, respectively). The FcMBL method identified more patient positive BCs than the Sepsityper® (25 of 25 vs 17 of 25), notably with 100% (3/3) sensitivity for clinical candidemia, compared to only 33% (1/3) for the Sepsityper®. Additionally, during inoculation experiments, the FcMBL method demonstrated a greater sensitivity, identifying 100% (24/24) of candida to genus level and 9/24 (37.5%) top species level compared to 70.8% (17/24) to genus and 6/24 to species (25%) using the Sepsityper®. This study demonstrates that capture and enrichment of samples using magnetic FcMBL-conjugated beads is superior to rapid centrifugation methods for identification of BCs by MALDI-TOF MS. Deploying the FcMBL method therefore offers potential clinical benefits in sensitivity and reduced turnaround times for BC diagnosis compared to the standard Sepsityper® kit, especially for fungal diagnosis. [ABSTRACT FROM AUTHOR]

Background: Indigenous peoples in high income countries are disproportionately affected by Type 2 Diabetes. Socioeconomic disadvantages and inadequate access to appropriate healthcare are important contributors. Objectives: This systematic review investigates effective designs of primary care management of Type 2 Diabetes for Indigenous adults in Australia, Canada, New Zealand, and the United States. Primary outcome was change in mean glycated haemoglobin. Secondary outcomes were diabetes-related hospital admission rates, treatment compliance, and change in weight or Body Mass Index. Methods: Included studies were critically appraised using Joanna Briggs Institute appraisal checklists. A mixed-method systematic review was undertaken. Quantitative findings were compared by narrative synthesis, meta-aggregation of qualitative factors was performed. Results: Seven studies were included. Three reported statistically significant reductions in means HbA1c following their intervention. Seven components of effective interventions were identified. These were: a need to reduce health system barriers to facilitate access to primary care (which the other six components work towards), an essential role for Indigenous community consultation in intervention planning and implementation, a need for primary care programs to account for and adapt to changes with time in barriers to primary care posed by the health system and community members, the key role of community-based health workers, Indigenous empowerment to facilitate community and self-management, benefit of short-intensive programs, and benefit of group-based programs. Conclusions: This study synthesises a decade of data from communities with a high burden of Type 2 Diabetes and limited research regarding health system approaches to improve diabetes-related outcomes. Policymakers should consider applying the seven identified components of effective primary care interventions when designing primary care approaches to mitigate the impact of Type 2 Diabetes in Indigenous populations. More robust and culturally appropriate studies of Type 2 Diabetes management in Indigenous groups are needed. Trail registration: Registered with PROSPERO (02/04/2021: CRD42021240098). [ABSTRACT FROM AUTHOR]

Synthetic biology has successfully advanced our ability to design and implement complex, time-varying genetic circuits to control the expression of recombinant proteins. However, these circuits typically require the production of regulatory genes whose only purpose is to coordinate expression of other genes. When designing very small genetic constructs, such as viral genomes, we may want to avoid introducing such auxiliary gene products while nevertheless encoding complex expression dynamics. To this end, here we demonstrate that varying only the placement and strengths of promoters, terminators, and RNase cleavage sites in a computational model of a bacteriophage genome is sufficient to achieve solutions to a variety of basic gene expression patterns. We discover these genetic solutions by computationally evolving genomes to reproduce desired gene expression time-course data. Our approach shows that non-trivial patterns can be evolved, including patterns where the relative ordering of genes by abundance changes over time. We find that some patterns are easier to evolve than others, and comparable expression patterns can be achieved via different genetic architectures. Our work opens up a novel avenue to genome engineering via fine-tuning the balance of gene expression and gene degradation rates. [ABSTRACT FROM AUTHOR]

The biggest nationwide COVID-19 pandemic lockdown worldwide was enforced in India for an initial period of 21-days. Emerging evidence suggests that pandemic situations and associated lockdowns have an adverse impact on sleep and mental health. However, prediction of sleep health from sociodemographic characteristics and the public's worry during the initial stages of the COVID-19 pandemic has not been extensively explored so far. It's also unclear whether sleep outcomes mediate the association between worry and mental health during pandemic situations. A web-survey (N = 391) on sociodemographic characteristics, COVID-19 related worry, sleep health (insomnia and daytime sleepiness), and depression was conducted during the initial 21-days of the COVID-19 stringent lockdown in India. Multiple regression analyses showed that variables, including sex, age, income level, and worry score, contributed to the significant regression equation for insomnia but not for daytime sleepiness. Specifically, the female, younger, lower income, and highly worried populations contributed significantly more than the male, elderly, higher income, and less worried populations, respectively, to the prediction of insomnia. Mediation analyses showed that insomnia, but not daytime sleepiness, fully mediated the relationship between worry score and severity of depressive symptoms. We provide evidence that the female, younger, lower income, and worried populations may be at higher risk for insomnia during pandemic situations. Current evidence gives hope that improving sleep may reduce depressive symptoms during a pandemic situation. This underscores the importance of the implementation of effective public health policies in conjunction with strategical responses to the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Adaptation of weeds to water stress could result in the broader distribution, and make weed control task increasingly difficult. Therefore, a clear understanding of the biology of weeds under water stress could assist in the development of sustainable weed management strategies. Avena fatua (wild oat) and A. ludoviciana (sterile oat) are problematic weeds in Australian winter crops. The objectives of this study were to determine the growth and reproductive behaviour of A. fatua and A. ludoviciana at different soil moisture levels [20, 40, 60, 80, and 100% water holding capacity (WHC)]. Results revealed that A. fatua did not survive and failed to produce seeds at 20 and 40% WHC. However, A. ludoviciana survived at 40% WHC and produced 54 seeds plant-1. A. fatua produced a higher number of seeds per plant than A. ludoviciana at 80 (474 vs 406 seeds plant-1) and 100% WHC (480 vs 417 seeds plant-1). Seed production for both species remained similar at 80 and 100% WHC; however, higher than 60% WHC. Seed production of A. fatua and A. ludoviciana was 235 and 282 seeds plant-1, respectively, at 60% WHC. The 60% WHC reduced seed production of A. fatua and A. ludoviciana by 51 and 32% respectively, compared to 100% WHC. The plant height, leaf weight, stem weight, and root weight per plant of A. fatua at 60% WHC reduced by 45, 27, 32, and 59%, respectively, as compared with 100% WHC. Similarly, the plant height, leaf weight, stem weight, and root weight per plant of A. ludoviciana at 60% WHC reduced by 45, 35, 47 and 76%, respectively, as compared with 100% WHC. Results indicate that A. ludoviciana can survive and produce seeds at 40% of WHC, indicating the adaptation of the species to dryland conditions. The results also suggest that A. ludoviciana is likely to be robust under water stress conditions, potentially reducing crop yield. The ability of A. fatua and A. ludoviciana to produce seeds under water-stressed conditions (60% WHC) necessitates integrated weed management strategies that suppress these weeds whilst taking into account the efficient utilization of stored moisture for winter crops. [ABSTRACT FROM AUTHOR]

Melanopsin is a visual pigment expressed in a small subset of ganglion cells in the mammalian retina known as intrinsically photosensitive retinal ganglion cells (ipRGCs) and is implicated in regulating non-image forming functions such as circadian photoentrainment and pupil constriction and contrast sensitivity in image formation. Mouse melanopsin's Carboxy-terminus (C-terminus) possesses 38 serine and threonine residues, which can potentially serve as phosphorylation sites for a G-protein Receptor Kinase (GRK) and be involved in the deactivation of signal transduction. Previous studies suggest that S388, T389, S391, S392, S394, S395 on the proximal region of the C-terminus of mouse melanopsin are necessary for melanopsin deactivation. We expressed a series of mouse melanopsin C-terminal mutants in HEK293 cells and using calcium imaging, and we found that the necessary cluster of six serine and threonine residues, while being critical, are insufficient for proper melanopsin deactivation. Interestingly, the additional six serine and threonine residues adjacent to the required six sites, in either proximal or distal direction, are capable of restoring wild-type deactivation of melanopsin. These findings suggest an element of plasticity in the molecular basis of melanopsin phosphorylation and deactivation. In addition, C-terminal chimeric mutants and molecular modeling studies support the idea that the initial steps of deactivation and β-arrestin binding are centered around these critical phosphorylation sites (S388-S395). The degree of functional versatility described in this study, along with ipRGC biophysical heterogeneity and the possible use of multiple signal transduction cascades, might contribute to the diverse ipRGC light responses for use in non-image and image forming behaviors, even though all six sub types of ipRGCs express the same melanopsin gene OPN4. [ABSTRACT FROM AUTHOR]

Objective: The passive leg raising (PLR) maneuver has become standard practice in fluid resuscitation. We aim to investigate the precision and consistency of the PLR for determining fluid responsiveness in critically ill patients and healthy volunteers using bioreactance non-invasive cardiac output monitoring (NiCOM™, Cheetah Medical, Inc., Newton Center, Massachusetts, USA). Methods: This study is prospective, single-center, observational cohort with repeated measures in critically ill patients admitted to the medical intensive care unit and healthy volunteers at a tertiary academic medical center. Three cycles of PLR were performed, each at 20–30 minutes apart. Fluid responsiveness was defined as a change in stroke volume index (ΔSVI) > 10% with each PLR as determined by NiCOM™. Precision was the variability in ΔSVI after the 3 PLR’s, and determined by range, average deviation and standard deviation. Consistency was the same fluid responsiveness determination of “Yes” (ΔSVI > 10%) or “No” (ΔSVI ≤ 10%) for all 3 PLR’s. Results: Seventy-five patients and 25 volunteers were enrolled. In patients, the precision was range of 17.2±13.3%, average deviation 6.5±4.0% and standard deviation 9.0±5.2%; and for volunteers, 17.4±10.3%, 6.6±3.8% and 9.0±6.7%, respectively. There was no statistical difference in the precision measurements between patients and volunteers. Forty-nine (65.3%) patients vs. twenty-four (96.0%) volunteers had consistent results, p < 0.01. Among those with consistent results, twenty-four (49.0%) patients and 24 (100%) volunteers were fluid responsive. Conclusions: The precision and consistency of determining ΔSVI with NiCOM™ after PLR may have clinical implication if ΔSVI > 10% is the absolute cutoff to determine fluid responsiveness. [ABSTRACT FROM AUTHOR]

The N-isopropylammelide isopropylaminohydrolase from Pseudomonas sp. strain ADP, AtzC, provides the third hydrolytic step in the mineralization of s-triazine herbicides, such as atrazine. We obtained the X-ray crystal structure of AtzC at 1.84 Å with a weak inhibitor bound in the active site and then used a combination of in silico docking and site-directed mutagenesis to understand the interactions between AtzC and its substrate, isopropylammelide. The substitution of an active site histidine residue (His249) for an alanine abolished the enzyme’s catalytic activity. We propose a plausible catalytic mechanism, consistent with the biochemical and crystallographic data obtained that is similar to that found in carbonic anhydrase and other members of subtype III of the amidohydrolase family [ABSTRACT FROM AUTHOR]

Pedestrian crowds often have been modeled as many-particle system including microscopic multi-agent simulators. One of the key challenges is to unearth governing principles that can model pedestrian movement, and use them to reproduce paths and behaviors that are frequently observed in human crowds. To that effect, we present a novel crowd simulation algorithm that generates pedestrian trajectories that exhibit the speed-density relationships expressed by the Fundamental Diagram. Our approach is based on biomechanical principles and psychological factors. The overall formulation results in better utilization of free space by the pedestrians and can be easily combined with well-known multi-agent simulation techniques with little computational overhead. We are able to generate human-like dense crowd behaviors in large indoor and outdoor environments and validate the results with captured real-world crowd trajectories. [ABSTRACT FROM AUTHOR]

The brain remains electrically and metabolically active during resting conditions. The low-frequency oscillations (LFO) of the blood oxygen level-dependent (BOLD) signal of functional magnetic resonance imaging (fMRI) coherent across distributed brain regions are known to exhibit features of this activity. However, these intrinsic oscillations may undergo dynamic changes in time scales of seconds to minutes during resting conditions. Here, using wavelet-transform based time-frequency analysis techniques, we investigated the dynamic nature of default-mode networks from intrinsic BOLD signals recorded from participants maintaining visual fixation during resting conditions. We focused on the default-mode network consisting of the posterior cingulate cortex (PCC), the medial prefrontal cortex (mPFC), left middle temporal cortex (LMTC) and left angular gyrus (LAG). The analysis of the spectral power and causal flow patterns revealed that the intrinsic LFO undergo significant dynamic changes over time. Dividing the frequency interval 0 to 0.25 Hz of LFO into four intervals slow-5 (0.01–0.027 Hz), slow-4 (0.027–0.073 Hz), slow-3 (0.073–0.198 Hz) and slow-2 (0.198–0.25 Hz), we further observed significant positive linear relationships of slow-4 in-out flow of network activity with slow-5 node activity, and slow-3 in-out flow of network activity with slow-4 node activity. The network activity associated with respiratory related frequency (slow-2) was found to have no relationship with the node activity in any of the frequency intervals. We found that the net causal flow towards a node in slow-3 band was correlated with the number of fibers, obtained from diffusion tensor imaging (DTI) data, from the other nodes connecting to that node. These findings imply that so-called resting state is not ‘entirely’ at rest, the higher frequency network activity flow can predict the lower frequency node activity, and the network activity flow can reflect underlying structural connectivity. [ABSTRACT FROM AUTHOR]

Ion channels are involved in many physiological processes and are attractive targets for therapeutic intervention. Their functional properties vary according to their subunit composition, which in turn varies in a developmental and tissue-specific manner and as a consequence of pathophysiological events. Understanding this diversity requires functional analysis of ion channel properties in large numbers of individual cells. Functional characterisation of ligand-gated channels involves quantitating agonist and drug dose-response relationships using electrophysiological or fluorescence-based techniques. Electrophysiology is limited by low throughput and high-throughput fluorescence-based functional evaluation generally does not enable the characterization of the functional properties of each individual cell. Here we describe a fluorescence-based assay that characterizes functional channel properties at single cell resolution in high throughput mode. It is based on progressive receptor activation and iterative fluorescence imaging and delivers >100 dose-responses in a single well of a 384-well plate, using α1-3 homomeric and αβ heteromeric glycine receptor (GlyR) chloride channels as a model system. We applied this assay with transiently transfected HEK293 cells co-expressing halide-sensitive yellow fluorescent protein and different GlyR subunit combinations. Glycine EC50 values of different GlyR isoforms were highly correlated with published electrophysiological data and confirm previously reported pharmacological profiles for the GlyR inhibitors, picrotoxin, strychnine and lindane. We show that inter and intra well variability is low and that clustering of functional phenotypes permits identification of drugs with subunit-specific pharmacological profiles. As this method dramatically improves the efficiency with which ion channel populations can be characterized in the context of cellular heterogeneity, it should facilitate systems-level analysis of ion channel properties in health and disease and the discovery of therapeutics to reverse pathological alterations. [ABSTRACT FROM AUTHOR]

Background: The global pandemic of Coronavirus infectious disease 2019 (COVID-19), caused by SARS-CoV-2, has plunged the world into both social and economic disarray, with vaccines still emerging and a continued paucity of personal protective equipment; the pandemic has also highlighted the potential for rapid emergence of aggressive respiratory pathogens and the need for preparedness. Avian immunoglobulins (IgY) have been previously shown in animal models to protect against new infection and mitigate established infection when applied intranasally. We carried out a proof-of-concept study to address the feasibility of using such antibodies as mucosally-applied prophylaxis against SARS-CoV-2. Methods: Hens were immunized with recombinant S1 spike glycoprotein of the virus, and the resulting IgY was evaluated for binding specificity, inhibition of glycoprotein binding to angiotensin converting enzyme-2 (ACE2) protein (the requisite binding site for the virus), and inhibition of viral replication in Vero cell culture. Results: Titers of anti-S1 glycoprotein IgY were evident in yolks at 14 days post-immunization, peaking at 21 days, and at peak concentrations of 16.8 mg/ml. IgY showed strong and significant inhibition of S1/ACE2 binding interactions, and significantly inhibited viral replication at a concentration of 16.8 mg/ml. Four weeks' collection from eggs of two hens produced a total of 1.55 grams of IgY. Conclusions: In this proof-of-concept study we showed that avian immunoglobulins (IgY) raised against a key virulence factor of the SARS-CoV-2 virus successfully inhibited the critical initial adhesion of viral spike glycoproteins to human ACE2 protein receptors and inhibited viral replication in vitro, in a short period using only two laying hens. We conclude that production of large amounts of IgY inhibiting viral binding and replication of SARS-CoV-2 is feasible, and that incorporation of this or similar material into an intranasal spray and/or other mucosal protecting products may be effective at reducing infection and spread of COVID-19. [ABSTRACT FROM AUTHOR]

Compression at a very low bit rate(≤0.5bpp) causes degradation in video frames with standard decoding algorithms like H.261, H.262, H.264, and MPEG-1 and MPEG-4, which itself produces lots of artifacts. This paper focuses on an efficient pre-and post-processing technique (PP-AFT) to address and rectify the problems of quantization error, ringing, blocking artifact, and flickering effect, which significantly degrade the visual quality of video frames. The PP-AFT method differentiates the blocked images or frames using activity function into different regions and developed adaptive filters as per the classified region. The designed process also introduces an adaptive flicker extraction and removal method and a 2-D filter to remove ringing effects in edge regions. The PP-AFT technique is implemented on various videos, and results are compared with different existing techniques using performance metrics like PSNR-B, MSSIM, and GBIM. Simulation results show significant improvement in the subjective quality of different video frames. The proposed method outperforms state-of-the-art de-blocking methods in terms of PSNR-B with average value lying between (0.7–1.9db) while (35.83–47.7%) reduced average GBIM keeping MSSIM values very close to the original sequence statistically 0.978. [ABSTRACT FROM AUTHOR]

In conservation agriculture systems, farmers gain many advantages from retaining crop residue on the soil surface, but crop residue retention in these systems may intervene with the activity of pre-emergence herbicides. A pot study was conducted to evaluate the effect of different rates of pre-emergence herbicides [imazethapyr (100 and 150 g a. i. ha-1), isoxaflutole (100 and 200 g a. i. ha-1), metolachlor (1.5 and 2.25 kg a. i. ha-1), pendimethalin (2.25 and 3.38 kg a. i. ha-1) and prosulfocarb + metolachlor (2.5 and 3.75 kg a. i. ha-1)] on seedling emergence and biomass of Echinochloa colona and Chloris virgata when applied in the presence of sorghum residue at rates equivalent to (0, 3 and 6 t ha-1). When seeds of E. colona and C. virgata were not covered with sorghum residue, the seedling emergence and biomass of both weeds was inhibited by 93–100% and 56–100%, respectively, with the application (both rates) of isoxaflutole, metolachlor, pendimethalin and prosulfocarb + metolachlor. Using sorghum residue resulted in lower herbicide efficacy on both weeds. At 3 t ha-1 sorghum residue, E. colona emergence and biomass reduced by 38–100% and 30–100%, respectively, with application of isoxaflutole, metolachlor and pendimethalin (both rates) in comparison with the no-herbicide treatment. Similarly, the emergence and biomass of C. virgata was also reduced by 92–100% and 25–100%, respectively. The results of this study suggest that crop residue may influence efficacy of commonly used pre-emergence herbicides and that the amount of crop residue on the soil surface should be adjusted according to the nature of the pre-emergence herbicides to achieve adequate weed control. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a long-term immune-mediated inflammatory disorder mainly, but not only, affecting skin, and is associated with significant medical and psychological morbidity. Evidence suggests that sleep is disrupted in psoriasis, however high quality empirical evidence is lacking. Given the importance of sleep for health, characterisation of sleep disruption in psoriasis is an important goal. We therefore conducted a systematic review of the sleep-psoriasis literature. Methods: Searches were conducted in Pubmed, SCOPUS and Web of Science from inception to May 2016. Studies were compared against inclusion/exclusion criteria and underwent a quality evaluation. Given the heterogeneity of studies, we conducted a narrative synthesis of the findings. Results: Searches revealed 32 studies which met our predetermined inclusion/exclusion criteria. Whilst 93.7% of studies reported sleep disruption in this population, ranging from 0.05% to 85.4%, many had important methodological shortcomings. Over half of all quantitative studies (54.8%; 17/31) relied on non-validated measures, contributing to heterogeneity in study findings. In those that employed valid measures, assessing sleep was often not the primary objective. We frequently found the absence of adequate sample size calculations and poor statistical reporting. Conclusion: This review showed that in psoriasis, reported sleep rates of sleep disturbance varied substantially. Most studies lacked a hypothesis driven research question and/or failed to use validated measures of sleep. We were unable to draw firm conclusions about the precise prevalence and nature of sleep disturbance within the psoriasis population. We offer suggestions to help advance understanding of sleep disturbance in psoriasis. [ABSTRACT FROM AUTHOR]

Protein interaction networks are a promising type of data for studying complex biological systems. However, despite the rich information embedded in these networks, these networks face important data quality challenges of noise and incompleteness that adversely affect the results obtained from their analysis. Here, we apply a robust measure of local network structure called common neighborhood similarity (CNS) to address these challenges. Although several CNS measures have been proposed in the literature, an understanding of their relative efficacies for the analysis of interaction networks has been lacking. We follow the framework of graph transformation to convert the given interaction network into a transformed network corresponding to a variety of CNS measures evaluated. The effectiveness of each measure is then estimated by comparing the quality of protein function predictions obtained from its corresponding transformed network with those from the original network. Using a large set of human and fly protein interactions, and a set of over GO terms for both, we find that several of the transformed networks produce more accurate predictions than those obtained from the original network. In particular, the measure and other continuous CNS measures perform well this task, especially for large networks. Further investigation reveals that the two major factors contributing to this improvement are the abilities of CNS measures to prune out noisy edges and enhance functional coherence in the transformed networks. [ABSTRACT FROM AUTHOR]

Loss of retinal ganglion cells (RGCs) in optic neuropathies results in permanent partial or complete blindness. Myocyte enhancer factor 2 (MEF2) transcription factors have been shown to play a pivotal role in neuronal systems, and in particular MEF2A knockout was shown to enhance RGC survival after optic nerve crush injury. Here we expanded these prior data to study bi-allelic, tri-allelic and heterozygous allele deletion. We observed that deletion of all MEF2A, MEF2C, and MEF2D alleles had no effect on RGC survival during development. Our extended experiments suggest that the majority of the neuroprotective effect was conferred by complete deletion of MEF2A but that MEF2D knockout, although not sufficient to increase RGC survival on its own, increased the positive effect of MEF2A knockout. Conversely, MEF2A over-expression in wildtype mice worsened RGC survival after optic nerve crush. Interestingly, MEF2 transcription factors are regulated by post-translational modification, including by calcineurin-catalyzed dephosphorylation of MEF2A Ser-408 known to increase MEF2A-dependent transactivation in neurons. However, neither phospho-mimetic nor phospho-ablative mutation of MEF2A Ser-408 affected the ability of MEF2A to promote RGC death in vivo after optic nerve injury. Together these findings demonstrate that MEF2 gene expression opposes RGC survival following axon injury in a complex hierarchy, and further support the hypothesis that loss of or interference with MEF2A expression might be beneficial for RGC neuroprotection in diseases such as glaucoma and other optic neuropathies. [ABSTRACT FROM AUTHOR]

Introduction: Advances in surgical techniques have improved clinical outcomes and decreased complications. At the same time, heightened attention to care quality has resulted in increased identification of hospital-acquired adverse events. We evaluated these divergent effects on the reported safety of lung cancer resection. Methods and materials: We analyzed hospital-acquired adverse events in patients undergoing lung cancer resection using the National Hospital Discharge Survey (NHDS) database from 2001–2010. Demographics, diagnoses, and procedures data were abstracted using ICD-9 codes. We used the Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicators (PSI) to identify hospital-acquired adverse events. Weighted analyses were performed using t-tests and chi-square. Results: A total of 302,444 hospitalizations for lung cancer resection and were included in the analysis. Incidence of PSI increased over time (28% in 2001–2002 vs 34% in 2009–2010; P<0.001). Those with one or more PSI had increased in-hospital mortality (aOR = 11.1; 95% CI, 4.7–26.1; P<0.001) and prolonged hospitalization (12.5 vs 7.8 days; P<0.001). However, among those with PSI, in-hospital mortality decreased over time, from 17% in 2001–2002 to 2% in 2009–2010. Conclusions: In a recent ten-year period, documented rates of adverse events associated with lung cancer resection increased. Despite this increase in safety events, we observed that mortality decreased. Because such metrics may be incorporated into hospital rankings and reimbursement considerations, adverse event coding consistency and content merit further evaluation. [ABSTRACT FROM AUTHOR]

Peanut (Arachis hypogaea L.) is an important nutrient-rich food legume and valued for its good quality cooking oil. The fatty acid content is the major determinant of the quality of the edible oil. The oils containing higher monounsaturated fatty acid are preferred for improved shelf life and potential health benefits. Therefore, a high oleic/linoleic fatty acid ratio is the target trait in an advanced breeding program. The two mutant alleles, ahFAD2A (on linkage group a09) and ahFAD2B (on linkage group b09) control fatty acid composition for higher oleic/linoleic ratio in peanut. In the present study, marker-assisted backcrossing was employed for the introgression of two FAD2 mutant alleles from SunOleic95R into the chromosome of ICGV06100, a high oil content peanut breeding line. In the marker-assisted backcrossing-introgression lines, a 97% increase in oleic acid, and a 92% reduction in linoleic acid content was observed in comparison to the recurrent parent. Besides, the oleic/linoleic ratio was increased to 25 with respect to the recurrent parent, which was only 1.2. The most significant outcome was the stable expression of oil-content, oleic acid, linoleic acid, and palmitic acid in the marker-assisted backcrossing-introgression lines over the locations. No significant difference was observed between high oleic and normal oleic in peanuts for seedling traits except germination percentage. In addition, marker-assisted backcrossing-introgression lines exhibited higher yield and resistance to foliar fungal diseases, i.e., late leaf spot and rust. [ABSTRACT FROM AUTHOR]

Calcium is the key macromineral having a role in skeletal structure and function, muscle contraction, and neurotransmission. Bone remodeling is maintained through a constant balance between calcium resorption and deposition. Calcium deficiency is resolved through calcium supplementation, and among the supplements, water-soluble organic molecules attracted great pharmaceutical interest. Calcium glucoheptonate is a highly water-soluble organic calcium salt having clinical use; however, detailed investigations on its biological effects are limited. We assessed the effects of calcium glucoheptonate on cell viability and proliferation of osteoblast-like MG-63 cells. Calcium uptake and mineralization were evaluated using Alizarin red staining of osteoblast-like MG-63 cells treated with calcium glucoheptonate. Expression of osteogenic markers were monitored by western blotting, immunofluorescence, and qRT-PCR assays. Increased proliferation and calcium uptake were observed in the MG-63 cells treated with calcium glucoheptonate. The treatment also increased the expression of osteopontin and osteogenic genes such as collagen-1, secreted protein acidic and cysteine rich (SPARC), and osteocalcin. Calcium glucoheptonate treatment did not exert any cytotoxicity on colorectal and renal epithelial cells, indicating the safety of the treatment. This is the first report with evidence for its beneficial effect for pharmaceutical use in addressing calcium deficiency conditions. [ABSTRACT FROM AUTHOR]

Interfacing anatomically conformal electronic components, such as sensors, with biology is central to the creation of next-generation wearable systems for health care and human augmentation applications. Thus, there is a need to establish computer-aided design and manufacturing methods for producing personalized anatomically conformal systems, such as wearable devices and human-machine interfaces (HMIs). Here, we show that a three-dimensional (3D) scanning and 3D printing process enabled the design and fabrication of a sensor-integrated anatomical human-machine interface (AHMI) in the form of personalized prosthetic hands that contain anatomically conformal electrode arrays for children affected by amniotic band syndrome, a common birth defect. A methodology for identifying optimal scanning parameters was identified based on local and global metrics of registered point cloud data quality. This method identified an optimal rotational angle step size between adjacent 3D scans. The sensitivity of the optimization process to variations in organic shape (i.e., geometry) was examined by testing other anatomical structures, including a foot, an ear, and a porcine kidney. We found that personalization of the prosthetic interface increased the tissue-prosthesis contact area by 408% relative to the non-personalized devices. Conformal 3D printing of carbon nanotube-based polymer inks across the personalized AHMI facilitated the integration of electronic components, specifically, conformal sensor arrays for measuring the pressure distribution across the AHMI (i.e., the tissue-prosthesis interface). We found that the pressure across the AHMI exhibited a non-uniform distribution and became redistributed upon activation of the prosthetic hand’s grasping action. Overall, this work shows that the integration of 3D scanning and 3D printing processes offers the ability to design and fabricate wearable systems that contain sensor-integrated AHMIs. [ABSTRACT FROM AUTHOR]

Acute exposure to light within the blue wavelengths has been shown to enhance alertness and vigilance, and lead to improved speed on reaction time tasks, possibly due to activation of the noradrenergic system. It remains unclear, however, whether the effects of blue light extend beyond simple alertness processes to also enhance other aspects of cognition, such as memory performance. The aim of this study was to investigate the effects of a thirty minute pulse of blue light versus placebo (amber light) exposure in healthy normally rested individuals in the morning during verbal memory consolidation (i.e., 1.5 hours after memory acquisition) using an abbreviated version of the California Verbal Learning Test (CVLT-II). At delayed recall, individuals who received blue light (n = 12) during the consolidation period showed significantly better long-delay verbal recall than individuals who received amber light exposure (n = 18), while controlling for the effects of general intelligence, depressive symptoms and habitual wake time. These findings extend previous work demonstrating the effect of blue light on brain activation and alertness to further demonstrate its effectiveness at facilitating better memory consolidation and subsequent retention of verbal material. Although preliminary, these findings point to a potential application of blue wavelength light to optimize memory performance in healthy populations. It remains to be determined whether blue light exposure may also enhance performance in clinical populations with memory deficits. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the ability of the glycolytic enzyme alpha-enolase (ENO1) or its immunodominant peptide (pEP1) to reduce the severity of CIA in DBA/1 mice when injected in a prophylactic way. Methods: Mice were treated with mouse ENO1 or pEP1 one day prior to collagen II immunization. Clinical assessment was evaluated using 4 parameters (global and articular scores, ankle thickness and weight). Titers of serum anti-ENO1, anti-cyclic citrullinated peptides (anti-CCP) and anti-CII (total IgG and IgG1/IgG2a isotypes) antibodies were measured by ELISA at different time-points. Disease activity was assessed by histological analysis of both anterior and hind paws at the end of experimentation. Results: Prophylactic injection of 100 μg of ENO1 reduced severity of CIA. Serum levels of anti-CII antibodies were reduced in ENO1-treated mice. Concordantly, ENO1-treated mice joints presented less severe histological signs of arthritis. ENO1 did not induce a shift toward a Th2 response since IgG1/IgG2a ratio of anti-CII antibodies remained unchanged and IL-4 serum levels were similar to those measured in the control group. Conclusions: Pre-immunization with ENO1 or its immunodominant peptide pEP1 reduces CIA severity at the clinical, immunological and histological levels. Effects of pEP1 were less pronounced. This immunomodulatory effect is associated with a reduction in anti-CII antibodies production but is not due to a Th1/Th2 shift. [ABSTRACT FROM AUTHOR]

Introduction: Optimizing methods for genital specimen collection to accurately characterize mucosal immune responses is a priority for the HIV prevention field. The menstrual cup (MC) has been proposed as an alternative to other methods including cervicovaginal lavage (CVL), but no study has yet formally compared these two methods. Methods: Forty HIV-infected, antiretroviral therapy-naïve women from the CAPRISA 002 acute HIV infection cohort study were randomized to have genital fluid collected using the MC with subsequent CVL, or by CVL alone. Qualitative data, which assessed levels of comfort and acceptability of MC using a 5-point Likert scale, was collected. Luminex multiplex assays were used to measure HIV-specific IgG against multiple gene products and 48 cytokines. Results: The majority (94%) of participants indicated that insertion, wearing and removal of the MC was comfortable. Nineteen MCs with 18 matching, subsequent CVLs and 20 randomized CVLs were available for analysis. Mucosal IgG responses against four HIV-antigens were detected in 99% of MCs compared to only 80% of randomized CVLs (p = 0.029). Higher specific antibody activity and total antibodies were observed in MCs compared to CVL (all p<0.001). In MCs, 42/48 (88%) cytokines were in the detectable range in all participants compared to 27/48 (54%) in CVL (p<0.001). Concentrations of 22/41 cytokines (53.7%) were significantly higher in fluid collected by MC. Both total IgG (r = 0.63; p = 0.005) and cytokine concentrations (r = 0.90; p<0.001) correlated strongly between MC and corresponding post-MC CVL. Conclusions: MC sampling improves the detection of mucosal cytokines and antibodies, particularly those present at low concentrations. MC may therefore represent an ideal tool to assess immunological parameters in genital secretions, without interfering with concurrent collection of conventional CVL samples. [ABSTRACT FROM AUTHOR]

A 6-chloronicotinic acid mineralizing bacterium was isolated from enrichment cultures originating from imidacloprid-contaminated soil samples. This Bradyrhizobiaceae, designated strain SG-6C, hydrolytically dechlorinated 6-chloronicotinic acid to 6-hydroxynicotinic acid, which was then further metabolised via the nicotinic acid pathway. This metabolic pathway was confirmed by growth and resting cell assays using HPLC and LC-MS studies. A candidate for the gene encoding the initial dechlorination step, named cch2 (for 6-̱chloronicotinic acid ̱chloro̱hydrolase), was identified using genome sequencing and its function was confirmed using resting cell assays on E. coli heterologously expressing this gene. The 464 amino acid enzyme was found to be a member of the metal dependent hydrolase superfamily with similarities to the TRZ/ ATZ family of chlorohydrolases. We also provide evidence that cch2 was mobilized into this bacterium by an Integrative and Conjugative Element (ICE) that feeds 6-hydroxynicotinic acid into the existing nicotinic acid mineralization pathway. [ABSTRACT FROM AUTHOR]

P2X7 is a homotrimeric ion channel with two transmembrane domains and a large extracellular ATP-binding domain. It plays a key role in the response of immune cells to danger signals released from cells at sites of inflammation. Gating of murine P2X7 can be induced by the soluble ligand ATP, as well as by NAD+-dependent ADP-ribosylation of arginine 125, a posttranslational protein modification catalyzed by the toxin-related ecto-enzymes ART2.1 and ART2.2. R125 is located at the edge of the ligand-binding crevice. Recently, an alternative splice variant of P2X7, designated P2X7(k), was discovered that differs from the previously described variant P2X7(a) in the N-terminal 42 amino acid residues composing the first cytosolic domain and most of the Tm1 domain. Here we compare the two splice variants of murine P2X7 with respect to their sensitivities to gating by ADP-ribosylation in transfected HEK cells. Our results show that the P2X7(k) variant is sensitive to activation by ADP-ribosylation whereas the P2X7(a) variant is insensitive, despite higher cell surface expression levels. Interestingly, a single point mutation (R276K) renders the P2X7(a) variant sensitive to activation by ADP-ribosylation. Residue 276 is located at the interface of neighboring subunits approximately halfway between the ADP-ribosylation site and the transmembrane domains. Moreover, we show that naive and regulatory T cells preferentially express the more sensitive P2X7(k) variant, while macrophages preferentially express the P2X7(a) variant. Our results indicate that differential splicing of alternative exons encoding the N-terminal cytosolic and transmembrane domains of P2X7 control the sensitivity of different immune cells to extracellular NAD+ and ATP. [ABSTRACT FROM AUTHOR]

Muscle potentially represents the most abundant source of autoantigens of the body and can be targeted by a variety of severe autoimmune diseases. Yet, the mechanisms of immunological tolerance toward muscle autoantigens remain mostly unknown. We investigated this issue in transgenic SM-Ova mice that express an ovalbumin (Ova) neo-autoantigen specifically in skeletal muscle. We previously reported that antigen specific CD4+ T cell are immunologically ignorant to endogenous Ova in this model but can be stimulated upon immunization. In contrast, Ova-specific CD8+ T cells were suspected to be either unresponsive to Ova challenge or functionally defective. We now extend our investigations on the mechanisms governing CD8+ tolerance in SM-Ova mice. We show herein that Ova-specific CD8+ T cells are not detected upon challenge with strongly immunogenic Ova vaccines even after depletion of regulatory T cells. Ova-specific CD8+ T cells from OT-I mice adoptively transferred to SM-Ova mice started to proliferate in vivo, acquired CD69 and PD-1 but subsequently down-regulated Bcl-2 and disappeared from the periphery, suggesting a mechanism of peripheral deletion. Peripheral deletion of endogenous Ova-specific cells was formally demonstrated in chimeric SM-Ova mice engrafted with bone marrow cells containing T cell precursors from OT-I TCR-transgenic mice. Thus, the present findings demonstrate that immunological tolerance to muscle autoantigens involves peripheral deletion of autoreactive CD8+ T cells. [ABSTRACT FROM AUTHOR]

Recent studies in patients suffering from inflammatory autoimmune myopathies suggested that moderate exercise training improves or at least stabilizes muscle strength and function without inducing disease flares. However, the precise mechanisms involved in this beneficial effect have not been extensively studied. Here we used a model of in vitro stretched C2C12 myoblasts to investigate whether mechanical stretch could influence myoblast proliferation or the expression of proinflammatory genes. Our results demonstrated that cyclic mechanical stretch stimulated C2C12 cell cycling and early up-regulation of the molecules related to mechanical-stretch pathway in muscle (calmodulin, nNOS, MMP-2, HGF and c-Met). Unexpectedly, mechanical stretch also reduced the expression of TLR3 and of proteins known to represent autoantigens in inflammatory autoimmune myopathies (Mi-2, HRS, DNA-PKcs, U1-70). Interestingly, stimulation or inhibition of calmodulin, NOS, HGF or c-Met molecules in vitro affected the expression of autoantigens and TLR3 proteins confirming their role in the inhibition of autoantigens and TLR3 during mechanical stretch. Overall, this study demonstrates for the first time that mechanical stretch could be beneficial by reducing expression of muscle autoantigens and of pro-inflammatory TLR3 and may provide new insight to understand how resistance training can reduce the symptoms associated with myositis. [ABSTRACT FROM AUTHOR]