Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacodynamic Profiling of Piperacillin in the Presence of Tazobactam in Patients through the Use of Population Pharmacokinetic Models and Monte Carlo Simulation

ABSTRACT The primary objectives of this analysis were to determine which pharmacokinetic model most accurately describes the elimination pathways for piperacillin in the presence of tazobactam through population pharmacokinetic modeling and to characterize its pharmacodynamic profile. Once the optimal pharmacokinetic model was identified, Monte Carlo simulation of 10,000 subjects with ADAPT II was performed to estimate the probability of attaining a target free-piperacillin concentration greater than the MIC for 50% of the dosing interval for 3.375 g every 6 h or every 4 h given as a 0.5-h infusion at each MIC between 0.25 and 32 μg/ml. In the population pharmacokinetic analysis, measurements of bias and precision, observed-predicted plots, and r2 values were highly acceptable for all three models and all three models were appropriate candidates for the Monte Carlo simulation evaluation. Visual comparison of the distribution of the piperacillin concentrations at the pharmacodynamic endpoint—h 3 concentrations of a 6-h dosing interval—between the simulated populations and raw data revealed that the linear model was most reflective of the raw data at the pharmacodynamic endpoint, and the linear model was therefore selected for the target attainment analysis. In the target attainment analysis, administration of 3 g of piperacillin every 6 h resulted in a robust target attainment rate that exceeded 95% for MICs of ≤8 mg/liter. The 4-h piperacillin administration interval had a superior pharmacodynamic profile and provided target attainment rates exceeding 95% for MICs of ≤16 mg/liter. This study indicates that piperacillin-tazobactam should have utility for empirical therapy of hospital-onset infections.
Effect of Erica sp. Honey against Microorganisms of Clinical Importance: Study of the Factors Underlying this Biological Activity

This study aimed to determine the factors (phenolic compounds, flavonoids, sugars or H2O2) that contribute the most to the antimicrobial activity of heather honey samples against four yeasts and four bacteria with medical importance. To discard the effect of H2O2 in the antimicrobial activity, catalase was added. To evaluate the osmotic pressure’s effect, artificial honey was also used. Phenolic compounds and flavonoids were determined and Pearson’s correlation analysis was performed to assess whether these correlated with antimicrobial activity. The amount of phenolic compounds ranged from 630.89 ± 5.21 GAE kg−1 to 718.92 ± 4.41 GAE kg−1, while the flavonoids varied between 450.72 ± 5.67 CAE kg−1 and 673.98 ± 4.33 CAE kg−1. For the bacteria, the minimum inhibitory concentration (MIC) of the honey without catalase ranged from 1.01 ± 0.50% to 10.00 ± 4.72% and was between 2.00 ± 0.94% and 13.27 ± 5.23% for honey with catalase. Concerning the yeasts, the MICs was between 13.16 ± 4.08% and 20.00 ± 5.09% for honey without catalase and between 14.95 ± 4.16% and 25.67 ± 5.50% for honey with catalase. The elucidation of the antimicrobial factors and action mechanisms is essential for the correct use of honey in therapeutic applications.
Strontium ranelate: ready for clinical use as disease-modifying osteoarthritis drug?

In the past decade, clinical practice in rheumatology has been transformed by the advent of ‘biologicals’. The use of these new drugs has significantly improved the outcome of patients with rheumatoid arthritis especially for those refractory to (patient-tailored) conventional disease-modifying antirheumatic drug (DMARD) therapy. The question is, is it now time for a gap-bridging, large step forward in the treatment of an even more commonly seen rheumatic disease, osteoarthritis? Has the era of the disease-modifying osteoarthritis drug (DMOAD) begun? Is ‘OA the new RA’ (quote from Professor P Conaghan, 2012 annual meeting of the British Society of Rheumatology (BSR)), or is this still wishful thinking? It no longer needs proclamation of worldwide numbers of patients who suffer from non-attendance and decreased productivity at work and unemployment, or costs of medical and paramedical care, medication use, and surgical treatments with joint replacement in the end, to recognise that osteoarthritis is a huge socioeconomic problem.1 Osteoarthritis is the most common disabling joint disease worldwide. Moreover, its incidence and prevalence are increasing because of ageing, higher life expectancy, and lifestyle changes, leading to a growing population of patients with osteoarthritis.2 Osteoarthritis is clinically characterised primarily by joint pain and consequently functional limitations. Cartilage degradation is still considered pivotal in its pathology. This might be considered surprising, since cartilage is not innervated, so osteoarthritic pain must arise from other tissues involved. Changes in periarticular bone, synovial tissue and other periarticular soft tissue structures such as ligaments and muscles are inextricably related to the osteoarthritic process. Obviously, all these structural changes are part of a cascade that eventually leads to overt osteoarthritis, and they need to be considered in unison when related to clinical symptoms. The sequence and relative importance of each of these processes may differ between individuals, between joints, between disease …
Association mapping for yield and grain quality traits in rice (Oryza sativa L.)

Association analysis was applied to a panel of accessions of Embrapa Rice Core Collection (ERiCC) with 86 SSR and field data from two experiments. A clear subdivision between lowland and upland accessions was apparent, thereby indicating the presence of population structure. Thirty-two accessions with admixed ancestry were identified through structure analysis, these being discarded from association analysis, thus leaving 210 accessions subdivided into two panels. The association of yield and grain-quality traits with SSR was undertaken with a mixed linear model, with markers and subpopulation as fixed factors, and kinship matrix as a random factor. Eight markers from the two appraised panels showed significant association with four different traits, although only one (RM190) maintained the marker-trait association across years and cultivation. The significant association detected between amylose content and RM190 was in agreement with previous QTL analyses in the literature. Herein, the feasibility of undertaking association analysis in conjunction with germplasm characterization was demonstrated, even when considering low marker density. The high linkage disequilibrium expected in rice lines and cultivars facilitates the detection of marker-trait associations for implementing marker assisted selection, and the mining of alleles related to important traits in germplasm.
Prediction of Freezing and Thawing Durability of Concrete Paving Blocks

This paper presents experimental results regarding freezing and thawing performance of various concrete paving blocks using a standard accelerated laboratory test, ASTM C 666, procedure A. A total of 124 paving blocks having eight different mixture proportions, prepared at optimum moisture content and fabricated at a commercial plant site, were used. The parameters investigated included bulk characteristics (density, absorption, and compressive and splitting tensile strength) and mass loss under various freezing and thawing cycles. It was found that ASTM C 666 can be utilized successfully to evaluate the relative performance of various paving blocks. Mass loss correlated well with the cement content (aggregate-cement ratio) and the bulk properties of the paving block samples. Minimum cement content, instead of minimum strength or maximum absorption, is the most suitable requirement for ensuring a reasonable freezing and thawing resistance for concrete paving blocks.
Enlargement of the Receptive Field Size to Low Intensity Mechanical Stimulation in the Rat Spinal Nerve Ligation Model of Neuropathy

One characteristic of plasticity after peripheral tissue or nerve damage is receptive field reorganization, and enlargement of receptive field size has been suggested to occur in certain models of neuropathic pain. The aim of the present study was to explore whether enlargement of neuronal receptive fields could contribute to the mechanical allodynia found on the ipsilateral paw in the spinal nerve ligation model of neuropathy. After ligation of L(5)-L(6) spinal nerves, all rats developed behavioral signs of mechanical allodynia, while the sham-operated control group displayed no such changes. The characteristics of the evoked responses of the neurones recorded in the dorsal horn of the rats were similar between the spinal nerve ligation, the sham operated control group, and the nonoperated control group, except for spontaneous activity, which was significantly increased in the spinal nerve ligation group. The mean size of the receptive field on the ipsilateral hindpaw, mapped using low-intensity stimulation with 9-g von Frey hair, was significantly increased in the spinal nerve ligation group, as compared to the sham-operated group. No significant difference was seen with 15- or 75-g von Frey hairs. The distribution of the receptive fields over the plantar surface of the paw was similar between the study groups. The enlargement of receptive field for non-noxious touch could be an indication of central sensitization in this model.
J C A P 0 9 ( 2 0 1 5 ) 0 0 7 ournal of C osmology and A stroparticle P hysics

Effective theories of a scalar φ invariant under the internal galileon symmetry φ→ φ+ bμx μ have been extensively studied due to their special theoretical and phenomenological properties. In this paper, we introduce the notion of weakly broken galileon invariance, which characterizes the unique class of couplings of such theories to gravity that maximally retain their defining symmetry. The curved-space remnant of the galileon’s quantum properties allows to construct (quasi) de Sitter backgrounds largely insensitive to loop corrections. We exploit this fact to build novel cosmological models with interesting phenomenology, relevant for both inflation and late-time acceleration of the universe.
X Radiation Causes a Persistent Induction of Reactive Oxygen Species and a Delayed Reinduction of TP53 in Normal Human Diploid Fibroblasts

Abstract Rugo, R. E. , Secretan, M. B. and Schiestl, R. H. X Radiation Causes a Persistent Induction of Reactive Oxygen Species and a Delayed Reinduction of TP53 in Normal Human Diploid Fibroblasts. Radiat. Res. 158, 210–219 (2002). Multiple genetic changes are required for the development of a malignant cell. The frequency of such changes in cancer cells is higher than can be explained through random mutation, and it was proposed that a subpopulation of cells develop a persistent mutator phenotype. Evidence for such a phenotype has been observed in mammalian cells after treatment with ionizing radiation. The mechanism that promotes this effect has not been defined, but proposed explanations include increased levels of reactive oxygen species (ROS) in irradiated cells and their progeny. The tumor suppressor TP53 is of prime importance in coordinating the cellular response to damage, and it has been suggested to have a role in regulating the cellular redox state. We investigated the persistence of induced levels of ROS in normal diploid human cells for 1 month after X-ray exposure and the role of TP53 in this oxidant response. X radiation induced an oxidant response that persisted for 2 weeks after exposure in cells with normal TP53 function. ROS levels in cells with abrogated TP53 function were decreased in magnitude and duration. X radiation caused a primary transient induction of TP53 followed by a reinduction of TP53 5 days after irradiation. This reinduction persisted for at least 2 days and coincided with the largest induction of apoptosis. The persistently elevated levels of ROS and delayed reinduction of TP53 reported here are further evidence of the delayed effects of ionizing radiation and add to the growing number of such observations.
Piecewise Disassembly of a Large-Herbivore Community across a Rainfall Gradient: The UHURU Experiment

Large mammalian herbivores (LMH) strongly influence plant communities, and these effects can propagate indirectly throughout food webs. Most existing large-scale manipulations of LMH presence/absence consist of a single exclusion treatment, and few are replicated across environmental gradients. Thus, important questions remain about the functional roles of different LMH, and how these roles depend on abiotic context. In September 2008, we constructed a series of 1-ha herbivore-exclusion plots across a 20-km rainfall gradient in central Kenya. Dubbed "UHURU" (Ungulate Herbivory Under Rainfall Uncertainty), this experiment aims to illuminate the ecological effects of three size classes of LMH, and how rainfall regimes shape the direction and magnitude of these effects. UHURU consists of four treatments: total-exclusion (all ungulate herbivores), mesoherbivore-exclusion (LMH >120-cm tall), megaherbivore-exclusion (elephants and giraffes), and unfenced open plots. Each treatment is replicated three times at three locations (“sites”) along the rainfall gradient: low (440 mm/year), intermediate (580 mm/year), and high (640 mm/year). There was limited variation across sites in soil attributes and LMH activity levels. Understory-plant cover was greater in plots without mesoherbivores, but did not respond strongly to the exclusion of megaherbivores, or to the additional exclusion of dik-dik and warthog. Eleven of the thirteen understory plant species that responded significantly to exclusion treatment were more common in exclusion plots than open ones. Significant interactions between site and treatment on plant communities, although uncommon, suggested that differences between treatments may be greater at sites with lower rainfall. Browsers reduced densities of several common overstory species, along with growth rates of the three dominant Acacia species. Small-mammal densities were 2–3 times greater in total-exclusion than in open plots at all sites. Although we expect patterns to become clearer with time, results from 2008–2012 show that the effects of excluding successively smaller-bodied subsets of the LMH community are generally non-additive for a given response variable, and inconsistent across response variables, indicating that the different LMH size classes are not functionally redundant. Several response variables showed significant treatment-by-site interactions, suggesting that the nature of plant-herbivore interactions can vary across restricted spatial scales.
Open-Door Laminoplasty for Cervical Myelopathy Resulting From Adjacent-Segment Disease in Patients With Previous Anterior Cervical Decompression and Fusion

Study Design. This is a retrospective study of patients with cervical myelopathy resulting from adjacent-segment disease who were treated by open-door expansive laminoplasty. Objectives. The purpose of this study was to evaluate the effectiveness of laminoplasty for cervical myelopathy resulting from adjacent-segment disease. Summary of Background Data. Adjacent-segment disease is one of the problems associated with anterior cervical decompression and fusion. However, the optimal surgical management strategy is still controversial. Methods. Thirty-one patients who underwent open-door expansive laminoplasty for cervical myelopathy resulting from adjacent-segment disease and age- and sex-matched 31 patients with myelopathy who underwent laminoplasty as the initial surgery were enrolled in the study. The pre- and postoperative Japanese Orthopedic Association scores (JOA scores) and the recovery rate were compared between the two groups. Results. The average JOA scores in the patients with adjacent-segment disease and the controls were 9.2 ± 2.6 and 9.4 ± 2.3 before the expansive laminoplasty and 11.9 ± 2.8 and 13.3 ± 1.7 at the follow-up examination, respectively; the average recovery rates in the two groups were 37.1 ± 22.4% and 50.0 ± 21.3%, respectively (P = 0.04). The mean number of segments covered by the high-intensity lesions on the T2-weighted magnetic resonance images was 1.87 and 0.9, respectively (P = 0.001). Conclusions. Moderate neurologic recovery was obtained after open-door laminoplasty in patients with cervical myelopathy resulting from adjacent-segment disc disease, although the results were not as satisfactory as those in the control group. This may be attributed to the irreversible damage of the spinal cord caused by persistent compression at the adjacent segments.
Post-traumatic stress disorder in occupational settings: anticipating and managing the risk.

BACKGROUND Post-traumatic stress disorder has had a substantial impact on employer liability for workplace psychological injury. The emergency services are an example of high-risk workforces that demand clear policies and procedures within an organization. The challenge is to minimize the injury to individuals and lessen the cost to organizations through the optimal application of preventative strategies. METHODS This field is not well represented in standard keyword searches and Medline was examined with linked fields of practice and research. Consensus guidelines that refer to this domain were also utilized. Few conclusions can be reached from the literature which directly examined occupational settings. RESULTS Organizations need to anticipate the possible traumatic exposures that may affect the workforce and have strategies to deal with the effects in the workplace, particularly the negative mental health outcomes in some personnel. This domain is relevant to all employers as accidents and violence are possible in most workplaces. Screening should be considered for high-risk individuals, particularly following a major traumatic event or cumulative exposure, such as in the emergency services. While psychological debriefing has no demonstrated benefit, the benefits of early intervention necessitate ready access to evidence-based treatments that have minimum barriers to care. Employers should be aware that distress may present indirectly in a similar way as conflict with management, poor performance and poor general health. CONCLUSION The knowledge about the impact of traumatic events obliges employers to have an active strategy to anticipate and manage the aftermath of such events as well as cumulative traumatic exposures.
Cell Origins and Diagnostic Accuracy of Interleukin 27 in Pleural Effusions

The objective of the present study was to investigate the presence of interleukin (IL)-27 in pleural effusions and to evaluate the diagnostic significance of pleural IL-27. The concentrations of IL-27 were determined in pleural fluids and sera from 68 patients with tuberculous pleural effusion, 63 malignant pleural effusion, 22 infectious pleural effusion, and 21 transudative pleural effusion. Flow cytometry was used to identify which pleural cell types expressed IL-27. It was found that the concentrations of pleural IL-27 in tuberculous group were significantly higher than those in malignant, infectious, and transudative groups, respectively. Pleural CD4+ T cells, CD8+ T cells, NK cells, NKT cells, B cells, monocytes, macrophages, and mesothelial cells might be the cell sources for IL-27. IL-27 levels could be used for diagnostic purpose for tuberculous pleural effusion, with the cut off value of 1,007 ng/L, IL-27 had a sensitivity of 92.7% and specificity of 99.1% for differential diagnosing tuberculous pleural effusion from non-tuberculous pleural effusions. Therefore, compared to non-tuberculous pleural effusions, IL-27 appeared to be increased in tuberculous pleural effusion. IL-27 in pleural fluid is a sensitive and specific biomarker for the differential diagnosing tuberculous pleural effusion from pleural effusions with the other causes.
Bone Morphogenetic Protein 2 Signaling Negatively Modulates Lymphatic Development in Vertebrate Embryos

Rationale: The emergence of lymphatic endothelial cells (LECs) seems to be highly regulated during development. Although several factors that promote the differentiation of LECs in embryonic development have been identified, those that negatively regulate this process are largely unknown. Objective: Our aim was to delineate the role of bone morphogenetic protein (BMP) 2 signaling in lymphatic development. Methods and Results: BMP2 signaling negatively regulates the formation of LECs. Developing LECs lack any detectable BMP signaling activity in both zebrafish and mouse embryos, and excess BMP2 signaling in zebrafish embryos and mouse embryonic stem cell–derived embryoid bodies substantially decrease the emergence of LECs. Mechanistically, BMP2 signaling induces expression of miR-31 and miR-181a in a SMAD-dependent mechanism, which in turn results in attenuated expression of prospero homeobox protein 1 during development. Conclusions: Our data identify BMP2 as a key negative regulator for the emergence of the lymphatic lineage during vertebrate development.
Acute renal response to LPS: impaired arginine production and inducible nitric oxide synthase activity.

We have previously shown in rats that lipopolysaccharide (LPS) causes both decreased renal perfusion and kidney arginine production before nitric oxide (NO) synthesis, resulting in a >30% reduction in plasma arginine. To clarify the early phase effects of LPS, we asked the following two questions: 1) is the rapid change in renal arginine production after LPS simply the result of decreased substrate (i.e., citrulline) delivery to the kidney or due to impaired uptake and conversion and 2) is the systemic production of NO limited by plasma arginine availability after LPS? Arterial and renal vein plasma was sampled at 30-min intervals from anesthetized rats with or without citrulline or arginine (2 micromol.min(-1). kg(-1) iv) a dose with no effect on MAP, renal function, or NO production. Exogenous citrulline was quickly converted to arginine by the kidney, resulting in plasma levels similar to equimolar arginine infusion. Also, the increase in citrulline uptake resulted primarily from increased filtered load and reabsorption. In a separate series, citrulline was infused after LPS administration, verifying that citrulline uptake and conversion persists during impaired kidney function. Last, in rats given LPS, the elevation of plasma arginine had no discernable impact on mean arterial pressure, kidney function, or systemic NO production. This work demonstrates how arginine synthesis is normally "substrate limited" and explains how impaired kidney perfusion quickly results in decreased plasma arginine. However, contrary to in vitro studies, the significant reduction in extracellular arginine during the early phase response to LPS in vivo is not functionally rate limiting for NO production.