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The cochlear nucleus (CN) transforms the spike trains of spiral ganglion cells into a set of sensory representations that are essential for auditory discriminations and perception. These transformations require the coordinated activity of different classes of neurons that are embryologically derived from distinct sets of precursors. Decades of investigation have shown that the neurons of the CN are differentiated by their morphology, neurotransmitter receptors, ion channel expression and intrinsic excitability. In the present study we have used linear discriminant analysis (LDA) to perform an unbiased analysis of measures of the responses of CN neurons to current injections to objectively categorize cells on the basis of both morphology and physiology. Recordings were made from cells in brain slices from CBA/CaJ mice and a transgenic mouse line, NF107, crossed against the Ai32 line. For each cell, responses to current injections were analyzed for spike rate, spike shape, input resistance, resting membrane potential, membrane time constant, hyperpolarization-activated sag and time constant. Cells were filled with dye for morphological classification, and visually classified according to published accounts. The different morphological classes of cells were separated with the LDA. Ventral cochlear nucleus (VCN) bushy cells, planar multipolar (T-stellate) cells, and radiate multipolar (D-stellate) cells were in separate clusters and separate from all of the neurons from the dorsal cochlear nucleus (DCN). Within the DCN, the pyramidal cells and tuberculoventral cells were largely separated from a distinct cluster of cartwheel cells. principal axes, whereas VCN cells were in 3 clouds approximately orthogonal to this plane. VCN neurons from the two mouse strains overlapped but were slightly separated, indicating either a strain dependence or differences in slice preparation methods. We conclude that cochlear nucleus neurons can be objectively distinguished based on their intrinsic electrical properties, but such distinctions are still best aided by morphological identification. [ABSTRACT FROM AUTHOR]

The profiles of polytraumatized patients in intensive care units were characterized. Serum and salivary markers were compared with normality between Classes I and II of APACHE II and between periods of hospitalization; these results were correlated. This was a prospective study on saliva charts and collection (n = 70). Profile: male, 27 years old, blunt traumas and collisions. Serum parameters with normality: decrease in pH, creatinine at admission to Class I, and at 48 and 72 hours in both classes; K+ at 48 h in Class II; Ca+ on admission in both classes and at 72 h in Class I. Increase in urea at 72 h in Class II, glucose at all times and in all classes, and Ca+ at 48 h in both classes. Class II had high Na+ at 48 and 72 h compared to Class I. In Class I, creatinine reduction occurred in 48 h and 72 h compared to admission and an increase of Ca+ at 48 h with admission. In Class II, pH and Na+ increased at 48 h and 72 h compared to admission. K+ decreased from admission to 48 h and increased from 48 h to 72 h. Urea increased from 48 to 72 hours. Creatinine decreased from admission to 48 and 72 hours. Ca+ increased from admission to 48 hours and decreased from 48 to 72 hours. There was an increase in the saliva levels in both classes and times in relation to normality. There was an increase in urea at admission, glucose at 72 h, and Ca+ at 48 h in Class II compared with Class I. Class I urea increased from admission to 48 h and Ca+ decreased from admission to 48 h. Class II urea decreased from 48 h to 72 h. Strong or very strong positive correlation was identified between blood and creatinine saliva at all times and regular and negative Ca+ at 72 h. This study provides evidence that salivary and serum biomarkers can be used together to monitor the evolution of the clinical symptoms of ICU patients. [ABSTRACT FROM AUTHOR]

Lutzomyia longipalpis is the main vector of Leishmania infantum, the causative agent of visceral leishmaniasis in the Neotropical realm. Its taxonomic status has been widely discussed once it encompasses a complex of species. The knowledge about the genetic structure of insect vector populations helps the elucidation of components and interactions of the disease ecoepidemiology. Thus, the objective of this study was to genotypically analyze populations of the Lu. longipalpis complex from a macrogeographic perspective using Next Generation Sequencing. Polymorphism analysis of three molecular markers was used to access the levels of population genetic structure among nine different populations of sand flies. Illumina Amplicon Sequencing Protocol® was used to identify possible polymorphic sites. The library was sequenced on paired-end Illumina MiSeq platform. Significant macrogeographical population differentiation was observed among Lu. longipalpis populations via PCA and DAPC analyses. Our results revealed that populations of Lu. longipalpis from the nine municipalities were grouped into three clusters. In addition, it was observed that the levels of Lu. longipalpis population structure could be associated with distance isolation. This new sequencing method allowed us to study different molecular markers after a single sequencing run, and to evaluate population and inter-species differences on a macrogeographic scale. [ABSTRACT FROM AUTHOR]

Visual hand gesture recognition systems are promising technologies for Human Computer Interaction, as they allow a more immersive and intuitive interaction. Most of these systems are based on the analysis of skeleton information, which is in turn inferred from color, depth, or near-infrared imagery. However, the robust extraction of skeleton information from images is only possible for a subset of hand poses, which restricts the range of gestures that can be recognized. In this paper, a real-time hand gesture recognition system based on a near-infrared device is presented, which directly analyzes the infrared imagery to infer static and dynamic gestures, without using skeleton information. Thus, a much wider range of hand gestures can be recognized in comparison with skeleton-based approaches. To validate the proposed system, a new dataset of near-infrared imagery has been created, from which good results that outperform other state-of-the-art strategies have been obtained. [ABSTRACT FROM AUTHOR]

Previous studies reported a significant association between postural control and lower-limb strength of several muscle groups, however, they were focused especially on knee muscles and ankle plantar and dorsal flexors. The aim of the present study is to examine the correlation between the muscle strength of ankle invertors, evertors, plantar flexors, and dorsal flexors and the control of bipedal stance in young and older adults. Thirty one young (aged 22.8 ± 2.6 years) and thirty one older adults (aged 70.5 ± 7.2 years) voluntarily participated in this study. Ankle muscle strength was evaluated by an isokinetic dynamometer. Normalized peak torque and work were averaged for four repetitions and for both lower limbs. The control of bipedal stance was evaluated by the sample entropy derived from an accelerometer placed on the lumbar spine while the subject stood on a foam pad with eyes open. Results showed significant age-related differences in ankle muscle strength and sample entropy in medial-lateral direction. More interestingly, the correlation between ankle muscle strength and the sample entropy was significantly different between young and older adults. Indeed, no significant correlation was observed in the younger adults. Conversely, in the older adults, the work of the ankle evertors positively correlated with sample entropy in the medial-lateral direction during bipedal stance (r = 0.36), whereas the peak torque and work of the dorsal flexors were significantly correlated with sample entropy in the anterior-posterior direction during bipedal stance (r = 0.44 for both variables). In the young adults, results suggest that, standing on foam with eyes open is a relatively easy postural task that does not require the full ankle muscle strength capacity. Taken together, the present findings suggest that older adults have a different association between ankle muscle strength and the sample entropy during bipedal stance. [ABSTRACT FROM AUTHOR]

Background: The high chances of getting latent tuberculosis infection (LTBI) among health care workers (HCWs) will an enormous problem in low and upper-middle-income countries. Method: Search strategies were done through both national and international databases include SID, Barakat knowledge network system, Irandoc, Magiran, Iranian national library, web of science, Scopus, PubMed/MEDLINE, OVID, EMBASE, the Cochrane library, and Google Scholar search engine. The Persian and the English languages were used as the filter in national and international databases, respectively. Medical Subject Headings (MeSH) terms was used to controlling comprehensive vocabulary. The search terms were conducted without time limitation till January 01, 2019. Results: The prevalence of LTBI in Iranian’s HCWs, based on the PPD test was 27.13% [CI95%: 18.64–37.7]. The highest prevalence of LTBI in Iranian’s HCWs were estimated 41.4% [CI95%: 25.4–59.5] in the north, and 33.8% [CI95%: 21.1–49.3] in the west. The lowest prevalence of LTBI was evaluated 18.2% [CI95%: 3.4–58.2] in the south of Iran. The prevalence of LTBI in Iranian’s HCWs who had work-experience more than 20 years old were estimated 20.49% [CI95%: 11–34.97]. In the PPD test, the prevalence of LTBI in Iranian’s HCWs who had received the Bacille Calmette–Guérin (BCG) was estimated 15% [CI95%: 3.6–47.73]. While, in the QFT, the prevalence of LTBI in Iranian’s HCWs in non-vaccinated was estimated 25.71% [CI95%: 13.96–42.49]. Conclusions: This meta-analysis shows the highest prevalence of LTBI in Iranian’s HCWs in the north and the west probably due to neighboring countries like Azerbaijan and Iraq, respectively. It seems that Iranian’s HCWs have not received the necessary training to prevent of TB. We also found that BCG was not able to protect Iranian’s HCWs from TB infections, completely. [ABSTRACT FROM AUTHOR]

The need for a validated set of emotional clips to elicit emotions in more ecological experiments is increasing. Here we present the validation of a new database of emotional films, named E-MOVIE, which includes, in this first validation phase, 39 excerpts arranged in six categories, three negative (Fear, Sadness and Compassion), two positive (Erotic and Scenery) and a Neutral category. Notably, Compassion and Scenery are new in the field as they were not included in other databases. The clips in E-MOVIE are characterized by homogenous durations of approximately two minutes, which make them suitable for psychophysiological research. In order to study the affective profile prompted by each category 174 participants (112 women) rated the movies on multiple dimensions, namely valence and arousal, intensity and discreteness of the induction of one of the six basic emotions and, finally, intensity of the experience of the emotional states defined by a series of emotional adjectives. Erotic clips were effective in the elicitation of a positive emotional state, characterized by high levels of arousal and excitement. On the other hand, Fear clips (selected without blood to avoid disgust reaction) prompted an affect characterized by high arousal, low valence and high levels of reported fear and anxiety. Women reported greater unpleasantness, distress, anxiety and jittery than men to the three negative categories. Compassion clips, characterized by the depiction of crying characters, were able to induce an affective state dominated by sadness and feeling touched, consistent with an empathic reaction to emotional sufferance. Sadness clips, instead, elicited an affective state characterized by sadness together with distress and angst. We also demonstrated that clips depicting natural environments (i.e. Scenery) prompted in the viewer a surprised, inspired affective state, characterized by high valence and arousal (especially in males), a result which suggests that their past categorization as neutral stimuli was inaccurate and problematic. [ABSTRACT FROM AUTHOR]

We developed an automated 2-tiered Fuhrman’s grading system for clear cell renal cell carcinoma (ccRCC). Whole slide images (WSI) and clinical data were retrieved for 395 The Cancer Genome Atlas (TCGA) ccRCC cases. Pathologist 1 reviewed and selected regions of interests (ROIs). Nuclear segmentation was performed. Quantitative morphological, intensity, and texture features (n = 72) were extracted. Features associated with grade were identified by constructing a Lasso model using data from cases with concordant 2-tiered Fuhrman’s grades between TCGA and Pathologist 1 (training set n = 235; held-out test set n = 42). Discordant cases (n = 118) were additionally reviewed by Pathologist 2. Cox proportional hazard model evaluated the prognostic efficacy of the predicted grades in an extended test set which was created by combining the test set and discordant cases (n = 160). The Lasso model consisted of 26 features and predicted grade with 84.6% sensitivity and 81.3% specificity in the test set. In the extended test set, predicted grade was significantly associated with overall survival after adjusting for age and gender (Hazard Ratio 2.05; 95% CI 1.21–3.47); manual grades were not prognostic. Future work can adapt our computational system to predict WHO/ISUP grades, and validating this system on other ccRCC cohorts. [ABSTRACT FROM AUTHOR]

Concentrations of free amino acids and [K+] in human sweat can be many times higher than in plasma. Conversely, [Na+] and [Cl-] in sweat are hypotonic to plasma. It was hypothesised that the amino acids and K+ were directly or indirectly associated with the resorption of Na+ and Cl- in the sweat duct. The implication would be that, as resources of these components became limiting during prolonged exercise then the capacity to resorb [Na+] and [Cl-] would diminish, resulting in progressively higher levels in sweat. If this were the case, then [Na+] and [Cl-] in sweat would have inverse relationships with [K+] and the amino acids during exercise. Forearm sweat was collected from 11 recreational athletes at regular intervals during a prolonged period of cycling exercise after 15, 25, 35, 45, 55 and 65 minutes. The subjects also provided passive sweat samples via 15 minutes of thermal stimulation. The sweat samples were analysed for concentrations of amino acids, Na+, Cl-, K+, Mg2+ and Ca2+. The exercise sweat had a total amino acid concentration of 6.4 ± 1.2mM after 15 minutes which was lower than the passive sweat concentration at 11.6 ± 0.8mM (p<0.05) and showed an altered array of electrolytes, indicating that exercise stimulated a change in sweat composition. During the exercise period, [Na+] in sweat increased from 23.3 ± 3.0mM to 34.6 ± 2.4mM (p<0.01) over 65 minutes whilst the total concentrations of amino acids in sweat decreased from 6.4 ± 1.2mM to 3.6 ± 0.5mM. [Na+] showed significant negative correlations with the concentrations of total amino acids (r = -0.97, p<0.05), K+ (r = -0.93, p<0.05) and Ca2+ (r = -0.83, p<0.05) in sweat. The results supported the hypothesis that amino acids and K+, as well as Ca2+, were associated with resorption of Na+ and Cl-. [ABSTRACT FROM AUTHOR]

The transport and distribution of charged molecules in polyelectrolyte solutions are of both fundamental and practical importance. A practical example, which is the specific subject addressed in the present paper, is the transport and distribution of charged species into cartilage. The charged species could be a contrast agent or a drug molecule involved in diagnosis or treatment of the widespread degenerative disease osteoarthritis, which leads to degradation of articular cartilage. Associated scientific issues include the rate of transport and the equilibrium concentrations of the charged species in the cartilage and the synovial fluid. To address these questions, we present results from magnetic resonance micro-imaging experiments on a model system of articular cartilage. The experiments yield temporally and spatially resolved data on the transport of a negatively charged contrast agent (charge = -2), used in medical examinations of cartilage, into a polyelectrolyte solution, which is designed to capture the electrostatic interactions in cartilage. Also presented is a theoretical analysis of the transport where the relevant differential equations are solved using finite element techniques as well as treated with approximate analytical expressions. In the analysis, non-ideal effects are included in the treatment of the mobile species in the system. This is made possible by using results from previous Monte Carlo simulations. The results demonstrate the importance of taking non-idealities into account when data from measurements of transport of charged solutes in a system with fixed charges from biological polyelectrolytes are analyzed. [ABSTRACT FROM AUTHOR]

Background and objective: To take full advantage of decision support, machine learning, and patient-level prediction models, it is important that models are not only created, but also deployed in a clinical setting. The KETOS platform demonstrated in this work implements a tool for researchers allowing them to perform statistical analyses and deploy resulting models in a secure environment. Methods: The proposed system uses Docker virtualization to provide researchers with reproducible data analysis and development environments, accessible via Jupyter Notebook, to perform statistical analysis and develop, train and deploy models based on standardized input data. The platform is built in a modular fashion and interfaces with web services using the Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) standard to access patient data. In our prototypical implementation we use an OMOP common data model (OMOP-CDM) database. The architecture supports the entire research lifecycle from creating a data analysis environment, retrieving data, and training to final deployment in a hospital setting. Results: We evaluated the platform by establishing and deploying an analysis and end user application for hemoglobin reference intervals within the University Hospital Erlangen. To demonstrate the potential of the system to deploy arbitrary models, we loaded a colorectal cancer dataset into an OMOP database and built machine learning models to predict patient outcomes and made them available via a web service. We demonstrated both the integration with FHIR as well as an example end user application. Finally, we integrated the platform with the open source DataSHIELD architecture to allow for distributed privacy preserving data analysis and training across networks of hospitals. Conclusion: The KETOS platform takes a novel approach to data analysis, training and deploying decision support models in a hospital or healthcare setting. It does so in a secure and privacy-preserving manner, combining the flexibility of Docker virtualization with the advantages of standardized vocabularies, a widely applied database schema (OMOP-CDM), and a standardized way to exchange medical data (FHIR). [ABSTRACT FROM AUTHOR]

The general population is exposed to bisphenol A (BPA) orally, parenterally, transdermally, and environmentally as a result of the use of BPA in food packaging, plastics, and personal care products. The majority of the population nowadays (91–99%) has detectable levels of BPA inside their body. In this study, we successfully performed an inexpensive, rapid, and simple protein precipitation procedure for extraction of BPA from human plasma, followed by analysis by LC-MS/MS. This method was specifically developed for handling large numbers of samples with minimum cost and volume of sample. The developed method was accurate, precise, and reproducible for quantification of BPA from human plasma samples in the concentration range of 10–2000 ng/mL. The method was performed on samples from 150 healthy volunteers who were enrolled in the study. The mean of observed BPA level was 2.22 ± 9.91 ng/mL. Higher BPA levels were observed for females compare to that of males (p-value = 0.002), the BPA levels were higher in participants 33 years of age and older compared to those less than 33 years of age (p-value = 0.000), then the BPA levels higher in subjects with tap water as source of drinking (p-value = 0.005). This method may be valuable for general risk assessment of BPA for a large and varied population because of its efficiency and economical aspects. [ABSTRACT FROM AUTHOR]

Background: Physical therapy can prevent functional impairments and improve the quality of life of patients after hospital discharge. However, the effect of early mobilization on patients with a critical illness remains unclear. This study was performed to assess the evidence available regarding the effect of early mobilization on critically ill patients in the intensive care unit (ICU). Methods: Electronic databases were searched from their inception to March 21, 2019. Randomized controlled trials (RCTs) comprising critically ill patients who received early mobilization were included. The methodological quality and risk of bias of each eligible trial were assessed using the Cochrane Collaboration tool. Data were extracted using a standard collection form each included study, and processed using the Mantel-Haenszel (M-H) or inverse-variance (I-V) test in the STATA v12.0 statistical software. Results: A total of 1,898 records were screened. Twenty-three RCTs comprising 2,308 critically ill patients were ultimately included. Early mobilization decreased the incidence of ICU-acquired weakness (ICU-AW) at hospital discharge (three studies, 190 patients, relative risk (RR): 0.60, 95% confidence interval (CI) [0.40, 0.90]; p = 0.013, I2 = 0.0%), increased the number of patients who were able to stand (one study, 50 patients, 90% vs. 62%, p = 0.02), increased the number of ventilator-free days (six studies, 745 patients, standardized mean difference (SMD): 0.17, 95% CI [0.02, 0.31]; p = 0.023, I2 = 35.5%) during hospitalization, increased the distance the patient was able to walk unassisted (one study, 104 patients, 33.4 (0–91.4) meters vs. 0 (0–30.4) meters, p = 0.004) at hospital discharge, and increased the discharged-to-home rate (seven studies, 793 patients, RR: 1.16, 95% CI [1.00, 1.34]; p = 0.046). The mortality (28-day, ICU and hospital) and adverse event rates were moderately increased by early mobilization, but the differences were statistically non-significant. However, due to the substantial heterogeneity among the included studies, and the low quality of the evidence, the results of this study should be interpreted with caution. Publication bias was not identified. Conclusions: Early mobilization appears to decrease the incidence of ICU-AW, improve the functional capacity, and increase the number of ventilator-free days and the discharged-to-home rate for patients with a critical illness in the ICU setting. [ABSTRACT FROM AUTHOR]

Background: It remains unknown which is the optimal first-line treatment regimen for patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). We performed a network meta-analysis to address this important issue. Methods: PubMed, Embase, Cochrane Library, Web of Science and major international scientific meetings were searched for relevant randomized controlled trials (RCTs). Progression-free survival (PFS) data was the primary outcome of interest, and overall survival (OS) and serious adverse events (SAEs) were the secondary outcomes of interests, reported as hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (CIs). Results: 25 RCTs with a total of 5005 patients randomized to receive seven treatments were included in the meta-analysis. Third-generation tyrosine kinase inhibitor (TKI) (osimertinib) and first-generation TKIs (F-TKIs) in combination with chemotherapy (F-TKIs+CT) were more effective than F-TKIs alone in terms of PFS (HR = 0.46, 95% CI: 0.22–0.93; P = 0.031 and HR = 0.62, 95% CI: 0.39–0.98; P = 0.041) and OS (HR = 0.63, 95% CI: 0.43–0.91; P = 0.014 and HR = 0.73, 95% CI: 0.57–0.92; P = 0.008). Second-generation TKIs (S-TKIs) showed significant OS advantage over F-TKIs (HR = 0.83, 95% CI: 0.70–0.99; P = 0.04). Based on treatment ranking in terms of PFS and OS, osimertinib had the highest probability of being the most effective treatment (89% and 86%) and with the best tolerability. F-TKIs+CT was ranked the second-most effective regimen, but with relatively high risk of SAEs. Conclusions: Osimertinib seemed to be the most preferable first-line treatment in advanced EGFR-mutated NSCLC. However, limitations of the study including a single RCT investigating osimertinib and immature OS data need to be considered. [ABSTRACT FROM AUTHOR]

Background: Diabetes is the most common comorbidity of necrotizing fasciitis (NF), but the effect of stress-induced hyperglycemia (SIH) on diabetic patients with NF has never been investigated. The aim of this study was to assess whether SIH, as determined by the glycemic gap between admission glucose levels and A1C-derived average glucose levels, predicts adverse outcomes in diabetic patients hospitalized with NF. Methods: We retrospectively reviewed the glycemic gap and clinical outcomes in 252 diabetic patients hospitalized due to NF from 2011 to 2018 in a single medical center in Taiwan. A receiver operating characteristic (ROC) curve was used to analyze the optimal cutoff values for predicting adverse outcomes. Univariate and multivariate logistic regression analyses were employed to identify significant predictors of adverse outcomes. Results: In total, 194 diabetic NF patients were enrolled. Compared with patients without adverse outcomes, patients with adverse outcomes had significantly higher glycemic gaps, Acute Physiology and Chronic Health Evaluation (APACHE) II scores and C-reactive protein (CRP) levels; lower albumin and hemoglobin levels; greater incidence of limb loss; and longer hospital and intensive care unit stays. The glycemic gap positively correlates with the laboratory risk indicator for NF scores, APACHE II scores and CRP levels. A glycemic gap of 146 mg/dL was the optimal cutoff value for predicting adverse outcomes using the ROC curve. Compared with patients with glycemic gaps ≤146 mg/dL, those with glycemic gaps >146 mg/dL had higher APACHE II scores and incidence rates of adverse outcomes, especially bacteremia and acute kidney injury. Multivariate analysis revealed that a glycemic gap >146 mg/dL and APACHE II score >15 were independent predictors of adverse outcomes, while the presence of hyperglycemia at admission was not. Conclusions: An elevated glycemic gap was significantly independently associated with adverse outcomes in diabetic NF patients. Further prospective studies are warranted to validate the role of the glycemic gap in NF patients with diabetes. [ABSTRACT FROM AUTHOR]

Introduction: The earliest changes in the brain due to Alzheimer’s disease are associated with the neural networks related to memory function. We investigated changes in functional and structural connectivity among regions that support memory function in prodromal Alzheimer’s disease, i.e., during the mild cognitive impairment (MCI) stage. Methods: Twenty-three older healthy controls and 25 adults with MCI underwent multimodal MRI scanning. Limbic white matter tracts–the fornix, parahippocampal cingulum, retrosplenial cingulum, subgenual cingulum and uncinate fasciculus–were reconstructed in ExploreDTI using constrained spherical deconvolution-based tractography. Using a network-of-interest approach, resting-state functional connectivity time-series correlations among sub-parcellations of the default mode and limbic networks, the hippocampus and the thalamus were calculated in Conn. Analysis: Controlling for age, education, and gender between group linear regressions of five diffusion-weighted measures and of resting state connectivity measures were performed per hemisphere. FDR-corrections were performed within each class of measures. Correlations of within-network Fisher Z-transformed correlation coefficients and the mean diffusivity per tract were performed. Whole-brain graph theory measures of cluster coefficient and average path length were inspecting using the resting state data. Results & conclusion: MCI-related changes in white matter structure were found in the fornix, left parahippocampal cingulum, left retrosplenial cingulum and left subgenual cingulum. Functional connectivity decreases were observed in the MCI group within the DMN-a sub-network, between the hippocampus and sub-areas -a and -c of the DMN, between DMN-c and DMN-a, and, in the right hemisphere only between DMN-c and both the thalamus and limbic-a. No relationships between white matter tract ‘integrity’ (mean diffusivity) and within sub-network functional connectivity were found. Graph theory revealed that changes in the MCI group was mostly restricted to diminished between-neighbour connections of the hippocampi and of nodes within DMN-a and DMN-b. [ABSTRACT FROM AUTHOR]

Agricultural activity, urban development and habitat alteration have caused the disappearance of the western spadefoot (Spea hammondii) from 80% of its geographic range in southern California. Despite the western spadefoot’s continuing decline, little research has been conducted on its natural history. The home range of adult spadefoots is unknown, and their use of upland habitat is poorly understood. Both factors are important for the long-term conservation of the species because adult spadefoots spend the majority of their lives away from breeding pools in self-excavated burrows. Between January 2012 and January 2013, we surgically implanted radio transmitters in 15 spadefoots at two locations and recorded their movements and habitat use. The mean distance moved between burrow locations was 18 m (SD ± 24.1 m, range1–204 m). The mean distance of burrows from the breeding pools was 40 m (SD ± 37.42 m, range 1–262 m). Rain was a significant predictor of spadefoot movement, with more rain predicting higher probability of movement and larger distances moved. At remote sensing scale (1 m) spadefoots selected grassland habitat for their burrow locations. At the microsite scale (< 1 m) spadefoots strongly selected duff over grass or shrub cover. Spadefoots burrowed in friable, sandy/loam soil with significantly less clay than random pseudoabsence points. This research enhances our understanding of a little-studied species and will contribute to the development of effective management plans for the western spadefoot. [ABSTRACT FROM AUTHOR]

HIV-1 gene expression is regulated by host and viral factors that interact with viral motifs and is influenced by proviral integration sites. Here, expression variation among integrants was followed for hundreds of individual proviral clones within polyclonal populations throughout successive rounds of virus and cultured cell replication, with limited findings using CD4+ cells from donor blood consistent with observations in immortalized cells. Tracking clonal behavior by proviral “zip codes” indicated that mutational inactivation during reverse transcription was rare, while clonal expansion and proviral expression states varied widely. By sorting for provirus expression using a GFP reporter in the nef open reading frame, distinct clone-specific variation in on/off proportions were observed that spanned three orders of magnitude. Tracking GFP phenotypes over time revealed that as cells divided, their progeny alternated between HIV transcriptional activity and non-activity. Despite these phenotypic oscillations, the overall GFP+ population within each clone was remarkably stable, with clones maintaining clone-specific equilibrium mixtures of GFP+ and GFP- cells. Integration sites were analyzed for correlations between genomic features and the epigenetic phenomena described here. Integrants inserted in the sense orientation of genes were more frequently found to be GFP negative than those in the antisense orientation, and clones with high GFP+ proportions were more distal to repressive H3K9me3 peaks than low GFP+ clones. Clones with low frequencies of GFP positivity appeared to expand more rapidly than clones for which most cells were GFP+, even though the tested proviruses were Vpr-. Thus, much of the increase in the GFP- population in these polyclonal pools over time reflected differential clonal expansion. Together, these results underscore the temporal and quantitative variability in HIV-1 gene expression among proviral clones that are conferred in the absence of metabolic or cell-type dependent variability, and shed light on cell-intrinsic layers of regulation that affect HIV-1 population dynamics. [ABSTRACT FROM AUTHOR]

The influenza A virus RNA-dependent RNA polymerase complex consists in three subunits, PB2, PB1 and PA, that perform transcription and replication of the viral genome through very distinct mechanisms. Biochemical and structural studies have revealed that the polymerase can adopt multiple conformations and form oligomers. However so far it remained unclear whether the available oligomeric crystal structures represent a functional state of the polymerase. Here we gained new insights into this question, by investigating the incompatibility between non-cognate subunits of influenza polymerase brought together through genetic reassortment. We observed that a 7:1 reassortant virus whose PB2 segment derives from the A/WSN/33 (WSN) virus in an otherwise A/PR/8/34 (PR8) backbone is attenuated, despite a 97% identity between the PR8-PB2 and WSN-PB2 proteins. Independent serial passages led to the selection of phenotypic revertants bearing distinct second-site mutations on PA, PB1 and/or PB2. The constellation of mutations present on one revertant virus was studied extensively using reverse genetics and cell-based reconstitution of the viral polymerase. The PA-E349K mutation appeared to play a major role in correcting the initial defect in replication (cRNA -> vRNA) of the PR8xWSN-PB2 reassortant. Strikingly the PA-E349K mutation, and also the PB2-G74R and PB1-K577G mutations present on other revertants, are located at a dimerization interface of the polymerase. All three restore wild-type-like polymerase activity in a minigenome assay while decreasing the level of polymerase dimerization. Overall, our data show that the polymerase subunits co-evolve to ensure not only optimal inter-subunit interactions within the heterotrimer, but also proper levels of dimerization of the heterotrimer which appears to be essential for efficient viral RNA replication. Our findings point to influenza polymerase dimerization as a feature that is controlled by a complex interplay of genetic determinants, can restrict genetic reassortment, and could become a target for antiviral drug development. [ABSTRACT FROM AUTHOR]

Predictive processing (e.g., predictive coding) is a predominant paradigm in cognitive neuroscience. This Primer considers the various levels of commitment neuroscientists have to the neuronal process theories that accompany the principles of predictive processing. Specifically, it reviews and contextualises a recent PLOS Biology study of alpha oscillations and travelling waves. We will see that alpha oscillations emerge naturally under the computational architectures implied by predictive coding-and may tell us something profound about recurrent message passing in brain hierarchies. Specifically, the bidirectional nature of forward and backward waves speaks to opportunities to understand attention and how it nuances bottom-up and top-down influences. [ABSTRACT FROM AUTHOR]

Predictive coding is a key mechanism to understand the computational processes underlying brain functioning: in a hierarchical network, higher levels predict the activity of lower levels, and the unexplained residuals (i.e., prediction errors) are passed back to higher layers. Because of its recursive nature, we wondered whether predictive coding could be related to brain oscillatory dynamics. First, we show that a simple 2-level predictive coding model of visual cortex, with physiological communication delays between levels, naturally gives rise to alpha-band rhythms, similar to experimental observations. Then, we demonstrate that a multilevel version of the same model can explain the occurrence of oscillatory traveling waves across levels, both forward (during visual stimulation) and backward (during rest). Remarkably, the predictions of our model are matched by the analysis of 2 independent electroencephalography (EEG) datasets, in which we observed oscillatory traveling waves in both directions. [ABSTRACT FROM AUTHOR]

Seasonal influenza is a sometimes surprisingly impactful disease, causing thousands of deaths per year along with much additional morbidity. Timely knowledge of the outbreak state is valuable for managing an effective response. The current state of the art is to gather this knowledge using in-person patient contact. While accurate, this is time-consuming and expensive. This has motivated inquiry into new approaches using internet activity traces, based on the theory that lay observations of health status lead to informative features in internet data. These approaches risk being deceived by activity traces having a coincidental, rather than informative, relationship to disease incidence; to our knowledge, this risk has not yet been quantitatively explored. We evaluated both simulated and real activity traces of varying deceptiveness for influenza incidence estimation using linear regression. We found that deceptiveness knowledge does reduce error in such estimates, that it may help automatically-selected features perform as well or better than features that require human curation, and that a semantic distance measure derived from the Wikipedia article category tree serves as a useful proxy for deceptiveness. This suggests that disease incidence estimation models should incorporate not only data about how internet features map to incidence but also additional data to estimate feature deceptiveness. By doing so, we may gain one more step along the path to accurate, reliable disease incidence estimation using internet data. This capability would improve public health by decreasing the cost and increasing the timeliness of such estimates. [ABSTRACT FROM AUTHOR]

Cognitive models suggest that social anxiety disorder (SAD) is maintained through the use of safety behaviours. Previous reports propose that these safety behaviours can be subdivided into two main categories: avoidance and impression management. Study 1 investigates whether certain safety behaviours are specific to SAD. The social behaviour questionnaire was administered to individuals with SAD (N = 106), post-traumatic stress disorder (N = 28) and non-patient controls (N = 59). A factor analysis (N = 164) replicated the previously reported avoidance and impression management subtypes. Scores for both subtypes were significantly higher in individuals with SAD than in individuals with post-traumatic stress disorder or non-patient controls. Study 2 investigated the causal role of such safety behaviours using an experimental design in a non-clinical population (N = 96). Pairs of participants each engaged in two conversations. In one of the conversations, a randomly selected participant performed either avoidance or impression management safety behaviours. In the other conversation, neither participant was instructed to use safety behaviours. Each participant rated their own anxiety and performance as well as rating the other person. Videos of the conversations were also rated. Both types of safety behaviour increased anxiety in the person performing the safety behaviour. The avoidance subtype also had broader effects on the other person that were largely absent from the impression management subtype. Taken together the studies provide support for the distinction between safety behaviour subtypes and have implications for the treatment of SAD. [ABSTRACT FROM AUTHOR]

Background: Patients with diabetes are at high risk of drug therapy problems (DTPs), as they are receiving multiple medications. To date, studies regarding DTPs in patients with diabetes in Ethiopia are limited. The aim of this study was to assess prevalence of DTPs, medication adherence and treatment satisfaction of patients with diabetes at Tikur Anbessa Specialized Hospital (TASH). Method: A cross-sectional study was conducted on randomly selected 418 participants who fulfilled the inclusion criteria. Data were collected using structured questionnaire and patients’ chart review. Cipolle’s classification system was used to determine DTPs. Modified Morisky’s Adherence Scale (MMAS-8) was used to measure patients’ adherence to their medication. Treatment Satisfaction with Medicines Questionnaire (SATMED-Q) patient satisfaction assessment questionnaire was used to assess patients’ treatment satisfaction. Results: A total of 207 DTPs in 177 (42.3%) of participants were identified. Commonly identified DTPs were dosage too low (58, 28.0%), ineffective drug therapy (54, 26.1%), and need additional drug therapy (52, 25.1%). Factors associated with DTPs were female gender (Adjusted Odds Ratio [AOR] = 2.31,95% CI:1.30–4.12); ≥3comorbidities (AOR = 3.61, 95% CI:1.19–10.96); ever married (AOR = 2.58,95% CI:1.23–5.48); type 2 diabetes (AOR = 5.62, 95% CI:1.21–26.04); non-adherence (AOR = 5.26,95% CI:2.51–11.04) and residence out of Addis Ababa (AOR = 0.30, 95% CI:0.12–0.73). Twenty four percent of participants were non-adherent to their drug therapies. Factors associated with non-adherence were diabetes complications (AOR = 2.00, 95% CI: 1.2–3.32), the female gender (AOR = 1.67, 95%CI: 1.01–2.8) and level of education (AOR = 0.42, 95%CI: 0.18–0.96). Eighty one percent of participants were satisfied with the current treatment. Conclusion: A significant proportion of patients were satisfied with their treatment and a quarter of the study participants were non-adherent to their medications at TASH diabetic clinic. However, DTPs were considerably higher among the study participants. Hence, future interventions targeting prevention and resolution of DTPs deemed to be necessary. [ABSTRACT FROM AUTHOR]

There is a vivid research on securely deliver a secret message by using a data hiding technique in digital images. However, most existing solutions of data-hiding need to encrypt secret data first, and embed the encrypt message into cover image, which is not promising any security once the embedding algorithm is leaked. In this paper, an efficient and adaptive data hiding scheme is presented which is based on a new reference matrix named secure reference matrix. The scheme is flexible enough to meet different data hiding capacities and image quality as needed, and we allow the reference matrix to be more secure since it is randomly generated each time and make it much harder for being attack with exhaustive manner by extending the possible solution. We give the detail protocol for our scheme and provide the practical test and performance analysis. Experimental results show that our scheme has a better flexibility and efficiency in embedding process, and the average value of Peak Signal to Noise Ratio (PSNR) for the stego-images which are generated by our scheme have a higher visual quality for different embedding capacities, and our scheme is more efficient compared with related work. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) were obtained from human bone marrow and amplified in cultures supplemented with human platelet lysate in order to generate myofibroblasts. When MSCs were seeded in solid collagen scaffolds, they differentiated into myofibroblasts that were observed to strongly bind to the substrate, forming a 3D cell scaffold network that developed tension and shortening after KCl stimulation. Moreover, MSC-laden scaffolds recapitulated the Frank-Starling mechanism so that active tension increased in response to increases in the initial length of the contractile system. This constituted a bioengineering tissue that exhibited the contractile properties observed in both striated and smooth muscles. By using the A. F. Huxley formalism, we determined the myosin crossbridge (CB) kinetics of attachment (f1) and detachment (g1 and g2), maximum myosin ATPase activity, molar myosin concentration, unitary CB force and maximum CB efficiency. CB kinetics were dramatically slow, characterizing the non-muscle myosin type IIA (NMMIIA) present in myofibroblasts. When MSCs were seeded in solid collagen scaffolds functionalized with Arg-Gly-Asp (RGD), contractility increased and CB kinetics were modified, whereas the unitary NMMIIA-CB force and maximum CB efficiency did not change. In conclusion, we provided a non-muscle bioengineering tissue whose molecular mechanical characteristics of NMMIIA were very close to those of a non-muscle contractile tissue such as the human placenta. [ABSTRACT FROM AUTHOR]

Research on pro-social rat behaviour is growing within the fields of comparative psychology and social neuroscience. However, much work remains on mapping important variables influencing this behaviour, and there is even disagreement on whether this behaviour is empathetically motivated and correctly labelled pro-social, or whether the behaviour is motivated by social contact. The present study used the helping behaviour paradigm where a rat can release a familiar cagemate from a restrainer. Prior to testing with a trapped cagemate, restrainer door opening was trained and baseline opening latencies when the restrainer was empty or baited with food were established. The findings show that the first-time release occurred sooner than in previous research and that rats used a previously demonstrated response to release the trapped cagemate. Further, rats opened the restrainer door more often and with shorter latencies when the restrainer contained a cagemate than when the restrainer was empty, but less often and with longer latencies than when the restrainer contained food. The test of whether illumination levels affect door-opening included in the study showed no effects. [ABSTRACT FROM AUTHOR]

Various methods have been devised to dissolve hydrogen gas in organ preservation solutions, including use of a hydrogen gas cylinder, electrolysis, or a hydrogen-generating agent. However, these methods require considerable time and effort for preparation. We investigated a practical technique for rapidly dissolving hydrogen gas in organ preservation solutions by using a canister containing hydrogen-absorbing alloy. The efficacy of hydrogen-containing organ preservation solution created by this method was tested in a miniature pig model of kidney transplantation from donors with circulatory arrest. The time required for dissolution of hydrogen gas was only 2–3 minutes. When hydrogen gas was infused into a bag containing cold ETK organ preservation solution at a pressure of 0.06 MPa and the bag was subsequently opened to the air, the dissolved hydrogen concentration remained at 1.0 mg/L or more for 4 hours. After warm ischemic injury was induced by circulatory arrest for 30 minutes, donor kidneys were harvested and perfused for 5 minutes with hydrogen-containing cold ETK solution or hydrogen-free cold ETK solution. The perfusion rate was faster from the initial stage with hydrogen-containing cold ETK solution than with hydrogen-free ETK solution. After storage of the kidney in hydrogen-free preservation solution for 1 hour before transplantation, no urine production was observed and blood flow was not detected in the transplanted kidney at sacrifice on postoperative day 6. In contrast, after storage in hydrogen-containing preservation solution for either 1 or 4 hours, urine was detected in the bladder and blood flow was confirmed in the transplanted kidney. This method of dissolving hydrogen gas in organ preservation solution is a practical technique for potentially converting damaged organs to transplantable organs that can be used safely in any clinical setting where organs are removed from donors. [ABSTRACT FROM AUTHOR]

Happiness, or Subjective Well-Being (SWB), is generally considered as a peaceful and satisfied state accompanied by consistent and optimistic mood. Due to its subjective and elusive nature, however, wellbeing has only been scarcely investigated in the neuroimaging literature. In this study, we investigated its neural substrates by characterizing two different perspectives: self- or other-concerned wellbeing. In the present study, 22 participants evaluated the subjective happiness (with button presses 1 to 4) to 3 categories (intra- and inter-personal and neutral) of pre-rated pictures in a slow event-related fMRI. Because wellbeing is constantly featured by pleasure feelings after self-inspection, we predict that happier conditions, featured by “intra-personal vs. neutral” and “inter-personal vs. neutral” conditions, should yield higher BOLD activities in overlapping reward- and self-related regions. Indeed, medial prefrontal (mPFC), pregenual ACC (pACC), precuneus and posterior cingulate cortex (PCC) were revealed both by General Linear Model (GLM) (categorical contrasts) and parametric modulations (correlations with rating 1-4s), specifically, more connectivity between nucleus accumbens (NAcc) and mPFC, via additional psychophysiological interaction, or PPI, analyses. More interestingly, GLM and multivariate searchlight analyses jointly reveal the subdivision of mPFC and the PCC/precuneus, with anterior mPFC and dorsal PCC/precuneus more for interpersonal, posterior mPFC and ventral PCC/precuneus more for intrapersonal, SWB, respectively. Taken together, these results are not only consistent with the “cortical midline hypothesis of the self”, but also extending the “spatial gradients of self-to-other-concerned processing” from mPFC to including both mPFC and PCC/precuneus, making them two “hubs” of self-to-other-concerned wellbeing network. [ABSTRACT FROM AUTHOR]

In order to support decision making on how to most effectively improve broiler welfare an innovative expert survey was conducted based on principles derived from semantic modelling. Twenty-seven experts, mainly broiler welfare scientists (n = 20; and 7 veterinarians), responded (response rate 38%) by giving welfare scores (GWS, scale 0–10) to 14 benchmarking housing systems (HSs), and explaining these overall scores by selecting, weighing and scoring main welfare parameters, including both input and output measures. Data exploration followed by REML (Linear Mixed Model) and ALM (Automatic Linear Modelling) analyses revealed 6 clusters of HSs, sorted from high to low welfare, i.e. mean GWS (with superscripts indicating significant differences): 1. (semi-natural backyard) Flock (8.8a); 2. Nature (7.7ab), Label Rouge II (7.4ab), Free range EU (7.2ab), Better Life (7.2ab); 3. Organic EU (7.0bc), Freedom Food (6.2bc); 4. Organic US (5.8bcd), Concepts NL (5.6abcdef), GAP 2 (4.9bcd); 5. Conventional EU (3.7de), Conventional US (2.9ef), Modern cage (2.9abcdef); 6. Battery cage (1.3f). Mean weighting factors (WF, scale 0–10) of frequently (n> = 15) scored parameters were: Lameness (8.8), Health status (8.6), Litter (8.3), Density (8.2), Air quality (8.1), Breed (8.0), Enrichment (7.0) and Outdoor (6.6). These did not differ significantly, and did not have much added value in explaining GWS. Effects of Role (Scientist/Vet), Gender (M/F) and Region (EU/non-EU) did not significantly affect GWS or WF, except that women provided higher WF than men (7.2 vs 6.4, p<0.001). The contribution of welfare components to overall welfare has been quantified in two ways: a) using the beta-coefficients of statistical regression (ALM) analyses, and b) using a semantic-modelling type (weighted average) calculation of overall scores (CalcWS) from parameter level scores (PLS) and WF. GWS and CalcWS were highly correlated (R = ~0.85). CalcWS identified Lameness, Health status, Density, Breed, Air quality and Litter as main parameters contributing to welfare. ALM showed that the main parameters which significantly explained the variance in GWS based on all PLS, were the output parameter Health status (with a beta-coefficient of 0.38), and the input parameters (stocking) Density (0.42), Litter (0.14) and Enrichment (0.27). The beta-coefficients indicated how much GWS would improve from 1 unit improvement in PLS for each parameter, thus the potential impact on GWS ranged from 1.4 welfare points for Litter to 4.2 points for Density. When all parameters were included, 81% of the variance in GWS was explained (77% for inputs alone; 39% for outputs alone). From this, it appears that experts use both input and output parameters to explain overall welfare, and that both are important. The major conventional systems and modern cages for broilers received low welfare scores (2.9–3.7), well below scores that may be considered acceptable (5.5). Also, several alternatives like GAP 2 (4.9), Concepts NL (5.6), Organic US (5.8) and Freedom Food (6.2) are unacceptable, or at risk of being unacceptable due to individual variation between experts and farms. Thus, this expert survey provides a preliminary semi-quantified decision-support tool to help determine how to most effectively improve broiler welfare in a wide range of HSs. [ABSTRACT FROM AUTHOR]

Purpose: Development of a supervised machine-learning model capable of predicting clinically relevant molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) from diffusion-weighted-imaging-derived radiomic features. Methods: The retrospective observational study assessed 55 surgical PDAC patients. Molecular subtypes were defined by immunohistochemical staining of KRT81. Tumors were manually segmented and 1606 radiomic features were extracted with PyRadiomics. A gradient-boosted-tree algorithm was trained on 70% of the patients (N = 28) and tested on 30% (N = 17) to predict KRT81+ vs. KRT81- tumor subtypes. A gradient-boosted survival regression model was fit to the disease-free and overall survival data. Chemotherapy response and survival were assessed stratified by subtype and radiomic signature. Radiomic feature importance was ranked. Results: The mean±STDEV sensitivity, specificity and ROC-AUC were 0.90±0.07, 0.92±0.11, and 0.93±0.07, respectively. The mean±STDEV concordance indices between the disease-free and overall survival predicted by the model based on the radiomic parameters and actual patient survival were 0.76±0.05 and 0.71±0.06, respectively. Patients with a KRT81+ subtype experienced significantly diminished median overall survival compared to KRT81- patients (7.0 vs. 22.6 months, HR 4.03, log-rank-test P = <0.001) and a significantly improved response to gemcitabine-based chemotherapy over FOLFIRINOX (10.14 vs. 3.8 months median overall survival, HR 2.33, P = 0.037) compared to KRT81- patients, who responded significantly better to FOLFIRINOX over gemcitabine-based treatment (30.8 vs. 13.4 months median overall survival, HR 2.41, P = 0.027). Entropy was ranked as the most important radiomic feature. Conclusions: The machine-learning based analysis of radiomic features enables the prediction of subtypes of PDAC, which are highly relevant for disease-free and overall patient survival and response to chemotherapy. [ABSTRACT FROM AUTHOR]

Background: In this research, an meta-analysis was performed for assessment of the associations between O6-methyguanine-DNA methyltransferase (MGMT) promoter hypermethylation possessing low-grade intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL), cervical cancer (CC), and clinicopathological characters of CC. Methods: Literature selection were conducted through searching PubMed, Web of science, EMBASE, China National Knowledge Infrastructure and Wanfang databases (up to November 2018). An assessment of associations between MGMT methylation and LSIL, HSIL, CC risk and clinicopathological characteristics was performed through pooled odds ratios (ORs) with relevant 95% confidence intervals (CIs). Subgroup analyses, meta-regressions and Galbraith plots were conducted to conduct an exploration on the possible sources of heterogeneity. The genome-wide DNA methylation array studies were extracted from Gene Expression Omnibus (GEO) databases for validation of these outcomes. Results: In this meta-analysis of 25 published articles, MGMT hypermethylation gradually elevated the rates among control group (12.16%), LSIL (20.92%), HSIL (36.33%) and CC (41.50%) specimens. MGMT promoter methylation was significant associated with the increased risk of LSIL by 1.74-fold (P<0.001), HSIL by 3.71-fold (P<0.001) and CC by 7.08-fold (P<0.001) compared with control. A significant association between MGMT promoter methylation with FIGO stage was also found (OR = 2.81, 95% CI: 1.79–4.41, p<0.001). The results of GEO datasets showed that 5 CpG sites in MGMT with a great diagnostic value for the screening of cervical cancer. Conclusion: The meta-analysis indicated the association between MGMT promoter hypermethylation and squamous intraepithelial lesion and cervical cancer. MGMT methylation detection might have a potential value to be an epigenetic marker for the clinical diagnosis of cervical cancer. [ABSTRACT FROM AUTHOR]

The objective was to evaluate vaginal temperature as a thermoregulatory response of Nellore heifers under different microclimatic conditions. The study was conducted during one year in an experimental area located at 54°37′W, 20°27′S, and 530 m of altitude in Brazil. Twenty-four Nellore females were reared in integrated crop-livestock-forestry systems with different shading patterns. The randomized complete block experimental design was utilized with a sub subdivided plots scheme, with plot corresponding to the production systems, the subplot to the season of the year, and the sub subplot, the hours of the day. To characterize the microclimate, data regarding air and black globe temperatures, and air relative humidity were collected and from them, temperature-humidity index was calculated. Vaginal temperature was obtained by using a bottom-type temperature logger (i-button) attached to an adapted intravaginal device. The black-globe temperature explained the variation on vaginal temperature. Increases on vaginal temperature were only observed, on average, two hours after the increase of black-globe temperature. The microclimatic conditions found in the systems, resulting from the various tree densities, modify the vaginal temperature in different degrees, demonstrating that the shading effect is not always accompanied by improvements in thermal comfort. The system with intermediate density showed a better microclimatic condition and, consequently, a lower increase in vaginal temperature. The interaction between air temperature, humidity and solar radiation resulted in adverse environmental conditions, however, Nellore heifers showed good adaptation to the environment. In conclusion, vaginal temperature is a good indicator to evaluate the thermoregulatory response in Nellore heifers. [ABSTRACT FROM AUTHOR]

Inertial measurement unit (IMU)-based gait analysis can be used to quantitatively analyze the bilateral coordination and gait asymmetry (GA). The purpose of this study was to investigate changes in bilateral coordination and GA due to gait speed using an IMU based gait analysis and identify spatiotemporal factors affecting bilateral coordination and GA. Eighty healthy adults (40 men and 40 women) participated in the study. The mean age was 26.2 years, and the mean body mass index was 22.8 kg/m2. Three different walking speeds (80%, 100%, and 120% of preferred walking speed) on a treadmill were applied for 1 min of continuous level walking using a shoe-type IMU-based gait analysis system. The phase coordination index (PCI) and GA were calculated on three different walking speeds. Several variables (gait speed, height, body mass index, cadence, and step length) were analyzed as possible factors affecting the PCI and GA. Bilateral coordination and GA improved during fast walking (p = 0.005 and p = 0.019, respectively) and deteriorated during slow walking (p<0.001 and p = 0.008, respectively), compared with the participants’ preferred walking speeds. The correlation analysis revealed that PCI was negatively correlated with step length at each walking condition and lower gait speed was negatively correlated with PCI and GA during slow walking. Both bilateral coordination and GA had a negative linear relationship with gait speed, showing an improvement in the fast walking condition and deterioration in the slow walking condition. Step length was the factor associated with the change in the bilateral coordination. [ABSTRACT FROM AUTHOR]

Objective: To identify risk factors associated with unfavorable outcomes in children with IgA vasculitis with nephritis (Henoch-Schőnlein purpura nephritis)(IgA-VN) Methods: PubMed, Embase, and Web of Science databases were searched for studies, published in English through February 2019. The data were extracted to perform pooled analysis, heterogeneity testing, subgroup analysis, sensitivity analysis, and publication bias analysis. Results: This meta-analysis showed that, older age at onset (WMD 1.77, 95% CI 0.35–3.18, p = 0.014), lower glomerular filtration rate (GFR; WMD -23.93, 95% CI -33.78- -14.09, p<0.0001), initial renal manifestations with nephrotic syndrome (OR 1.74, 95% CI 1.12–2.70, p = 0.013), with nephritic-nephrotic syndrome (OR 4.55, 95% CI 2.89–7.15, p<0.0001) and renal biopsy with crescentic nephritis (International Study of Kidney Disease in Children [ISKDC] grades III-V) (OR 3.85, 95% CI 2.37–6.28, p<0.0001) were significant risk factors associated with poor outcomes in IgA-VN, whereas initial clinical features with hematuria (OR 0.33, 95% CI 0.16–0.69, p = 0.003) and mild proteinuria±hematuria (OR 0.46, 95% CI 0.28–0.75, p<0.0001) were associated with progression to good outcomes. By contrast, gender, hypertension and initial renal manifestations of acute nephritic syndrome were not significantly associated with poor outcomes in IgA-VN. Conclusion: This meta-analysis showed that older age at onset, lower GFR, initial renal features of nephrotic syndrome and nephritic-nephrotic syndrome and renal biopsy with crescentic nephritis (ISKDC grades III-V) were predictive of poor prognosis in children with IgA-VN. [ABSTRACT FROM AUTHOR]

Electrical impedance myography (EIM) is a technique for the assessment of muscle health and composition and has been shown to be sensitive to a variety of muscle pathologies including neurogenic atrophy and connective tissue deposition. However, it has been minimally studied in pure inflammation. In this study, we sought to assess EIM sensitivity to experimental inflammation induced by the localized intramuscular injection of λ-carrageenan. A total of 91 mice underwent 1–1000 kHz EIM measurements of gastrocnemius using a needle array, followed by injection of either 0.3% λ-carrageenan in phosphate-buffered saline (PBS) or PBS alone. Animals were then remeasured with EIM at 4, 24, 48, or 72 hours and euthanized and quantitative assessment of muscle histology was performed. Parallel alterations in both 5 and 50 kHz EIM values were identified at 4 and 24 hours, including reductions in phase, reactance, and resistance. In PBS-treated animals these values normalized by 48 hours, whereas substantial reductions in phase and reactance in 5 kHz EIM values persisted at 48 and 72 hours (i.e., values of phase 72 hours post-injection were 6.51 ± 0.40 degrees for λ-carrageenan versus 8.44 ± 0.35 degrees for PBS p<0.001, n = 11 per group). The degree of basophilic area observed in muscle sections by histology correlated to the degree of phase change at these two time points (Rspearman = -0.51, p = 0.0029). Changes in low frequency EIM parameters are sensitive to the presence of inflammatory infiltrates, and have the potential of serving as a simple means of quantifying the presence and extent of muscle inflammation without the need for biopsy. [ABSTRACT FROM AUTHOR]

Background: Toxigenic Vibrio cholerae resides in aquatic reservoirs of cholera-endemic areas mostly in a dormant form known as conditionally viable environmental cells (CVEC) in which the bacteria remain embedded in an exopolysaccharide matrix, and fail to grow in routine bacteriological culture. The CVEC can be resuscitated by supplementing culture media with either of two autoinducers CAI-1 and AI-2, which are signal molecules controlling quorum sensing, a regulatory network of bacterial gene expression dependent on cell density. This study investigated possible existence of variant strains that overproduce AIs, sufficient to resuscitate CVEC in environmental waters. Methods: Environmental V. cholerae isolates and Tn insertion mutants of a V. cholerae strain C6706 were screened for production of AIs using bioluminescent reporter strains. Relevant mutations in environmental strains which overproduced AI-2 were characterized by nucleotide sequencing and genetic complementation studies. Effect of AIs produced in culture supernatants of relevant strains on reactivation of CVEC in water was determined by resuscitation assays. Results: Two of 54 environmental V. cholerae isolates were found to overproduce AI-2. Screening of a Tn-insertion library of V. cholerae strain C6706, identified a mutant which overproduced AI-2, and carried Tn insertion in the cqsS gene. Nucleotide sequencing also revealed mutations inactivating the cqsS gene in environmental isolates which overproduced AI-2, and this property was reversed when complemented with a wild type cqsS gene. Culture of river water samples supplemented with spent medium of these mutants resuscitated dormant V. cholerae cells in water. Significance: V. cholerae strains with inactivated cqsS gene may offer a convenient source of AI-2 in enhanced assays for monitoring bacteriological quality of water. The results also suggest a potential role of naturally occurring cqsS mutants in the environmental biology of V. cholerae. Furthermore, similar phenomenon may have relevance in the ecology of other waterborne bacterial pathogens beyond V. cholerae. [ABSTRACT FROM AUTHOR]

Background and objectives: The construction of whole-body magnetic resonance (MR) imaging atlases allows to perform statistical analysis with applications in anomaly detection, longitudinal, and correlation studies. Atlas-based methods require a common coordinate system to which all the subjects are mapped through image registration. Optimisation of the reference space is an important aspect that affects the subsequent analysis of the registered data, and having a reference space that is neutral with respect to local tissue volume is valuable in correlation studies. The purpose of this work is to generate a reference space for whole-body imaging that has zero voxel-wise average volume change when mapped to a cohort. Methods: This work proposes an approach to register multiple whole-body images to a common template using volume changes to generate a synthetic reference space, starting with an initial reference and refining it by warping it with a deformation that brings the voxel-wise average volume change associated to the mappings of all the images in the cohort to zero. Results: Experiments on fat/water separated whole-body MR images show how the method effectively generates a reference space neutral with respect to volume changes, without reducing the quality of the registration nor introducing artefacts in the anatomy, while providing better alignment when compared to an implicit reference groupwise approach. Conclusions: The proposed method allows to quickly generate a reference space neutral with respect to local volume changes, that retains the registration quality of a sharp template, and that can be used for statistical analysis of voxel-wise correlations in large datasets of whole-body image data. [ABSTRACT FROM AUTHOR]

Many animals are able to sense the earth’s magnetic field, including varieties of arthropods and members of all major vertebrate groups. While the existence of this magnetic sense is widely accepted, the mechanism of action remains unknown. Building from recent work on synthetic magnetoreceptors, we propose a new model for natural magnetosensation based on the rotating magnetocaloric effect (RME), which predicts that heat generated by magnetic nanoparticles may allow animals to detect features of the earth’s magnetic field. Using this model, we identify the conditions for the RME to produce physiological signals in response to the earth’s magnetic field and suggest experiments to distinguish between candidate mechanisms of magnetoreception. [ABSTRACT FROM AUTHOR]

Tight junctions (TJs) are cellular junctions within the mammalian epithelial cell sheet that function as a physical barrier to molecular transport within the intercellular space. Dysregulation of TJs leads to various diseases. Tricellular TJs (tTJs), specialized structural variants of TJs, are formed by multiple transmembrane proteins (e.g., lipolysis-stimulated lipoprotein receptor [LSR] and tricellulin) within tricellular contacts in the mammalian epithelial cell sheet. However, the mechanism for recruiting LSR and tricellulin to tTJs is largely unknown. Previous studies have identified that tyrphostin 9, the dual inhibitor of Pyk2 (a nonreceptor tyrosine kinase) and receptor tyrosine kinase platelet-derived growth factor receptor (PDGFR), suppresses LSR and tricellulin recruitment to tTJs in EpH4 (a mouse mammary epithelial cell line) cells. In this study, we investigated the effect of Pyk2 inhibition on LSR and tricellulin localization to tTJs. Pyk2 inactivation by its specific inhibitor or repression by RNAi inhibited the localization of LSR and downstream tricellulin to tTJs without changing their expression level in EpH4 cells. Pyk2-dependent changes in subcellular LSR and tricellulin localization were independent of c-Jun N-terminal kinase (JNK) activation and expression. Additionally, Pyk2-dependent LSR phosphorylation at Tyr-237 was required for LSR and tricellulin localization to tTJs and decreased epithelial barrier function. Our findings indicated a novel mechanism by which Pyk2 regulates tTJ assembly and epithelial barrier function in the mammalian epithelial cell sheet. [ABSTRACT FROM AUTHOR]

Background: Delirium is the most common postoperative complication of the central nervous system (CNS) that can trigger long-term cognitive impairment. Its underlying mechanism is not fully understood, but the dysfunction of the blood-brain barrier (BBB) has been implicated. The serum levels of the axonal damage biomarker, phosphorylated neurofilament heavy subunit (pNF-H) increase in moderate to severe delirium patients, indicating that postoperative delirium can induce irreversible CNS damage. Here, we investigated the relationship among postoperative delirium, CNS damage and BBB dysfunction, using pNF-H as reference. Methods: Blood samples were collected from 117 patients within 3 postoperative days. These patients were clinically diagnosed with postoperative delirium using the Confusion Assessment Method for the Intensive Care Unit. We measured intercellular adhesion molecule-1, platelet and endothelial cell adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and P-selectin as biomarkers for BBB disruption, pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6), and pNF-H. We conducted logistic regression analysis including all participants to identify independent biomarkers contributing to serum pNF-H detection. Next, by multiple regression analysis with a stepwise method we sought to determine which biomarkers influence serum pNF-H levels, in pNF-H positive patients. Results: Of the 117 subjects, 41 were clinically diagnosed with postoperative delirium, and 30 were positive for serum pNF-H. Sensitivity and specificity of serum pNF-H detection in the patients with postoperative delirium were 56% and 90%, respectively. P-selectin was the only independent variable to associate with pNF-H detection (P < 0.0001) in all 117 patients. In pNF-H positive patients, only PECAM-1 was associated with serum pNF-H levels (P = 0.02). Conclusions: Serum pNF-H could be an objective delirium biomarker, superior to conventional tools in clinical settings. In reference to pNF-H, P-selectin may be involved in the development of delirium-related CNS damage and PECAM-1 may contribute to the progression of delirium- related CNS damage. [ABSTRACT FROM AUTHOR]

Aim: To assess the effect of Lactobacillus supplementation on Helicobacter pylori eradication rates and side effects of the triple therapy. Methods: PubMed, Embase, Web of Science and Cochrane Library were searched for articles published up to July, 2019. Review Manager 5.3 and Stata 12.0 were used for statistical analyses. Results: The initial database search resulted in 852 articles. Through exclusion and screening, 11 randomized controlled trials involving a total of 724 patients were finally included in this meta-analysis. The H. pylori elimination rate in the Lactobacillus supplement group was significantly higher than that in the control group (RR 1.16, 95% CI 1.08–1.25, P<0.0001). Subgroup analysis showed that the eradication rates were significantly enhanced in both adults and children group, and no significant difference was detected between Asia and Europe group. In addition, sub-analysis based on duration of Lactobacillus supplementation showed the pooled RRs in the long-term and short-term groups were 1.17 (95%CI 1.06–1.30) and 1.16 (95% CI 1.04–1.30), respectively. Regarding the Lactobacillus strains, the pooled RR was 1.33 (95% CI 1.10–1.62) in the L. casei group, 1.18 (95% CI 1.03–1.34) in the L. reuteri group while 1.02 (95% CI 0.87–1.21) in the Lactobacillus GG group. As for the total side effects, Lactobacillus supplementation significantly reduced the incidence of taste disturbance (RR = 0.36, 95% CI 0.17–0.74, P = 0.005). Conclusions: Lactobacillus supplementation during the treatment of Helicobacter pylori infection can effectively improve the eradication rates, and reduce the incidence of therapy-related taste disturbance. [ABSTRACT FROM AUTHOR]

Humans and other animals effortlessly identify natural sounds and categorize them into behaviorally relevant categories. Yet, the acoustic features and neural transformations that enable sound recognition and the formation of perceptual categories are largely unknown. Here, using multichannel neural recordings in the auditory midbrain of unanesthetized female rabbits, we first demonstrate that neural ensemble activity in the auditory midbrain displays highly structured correlations that vary with distinct natural sound stimuli. These stimulus-driven correlations can be used to accurately identify individual sounds using single-response trials, even when the sounds do not differ in their spectral content. Combining neural recordings and an auditory model, we then show how correlations between frequency-organized auditory channels can contribute to discrimination of not just individual sounds but sound categories. For both the model and neural data, spectral and temporal correlations achieved similar categorization performance and appear to contribute equally. Moreover, both the neural and model classifiers achieve their best task performance when they accumulate evidence over a time frame of approximately 1–2 seconds, mirroring human perceptual trends. These results together suggest that time-frequency correlations in sounds may be reflected in the correlations between auditory midbrain ensembles and that these correlations may play an important role in the identification and categorization of natural sounds. [ABSTRACT FROM AUTHOR]