Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroprotective Efficacy and Pharmacokinetic Behavior of Novel Anti-Inflammatory Para-Phenyl Substituted Diindolylmethanes in a Mouse Model of Parkinson’s Disease

There are currently no registered drugs that slow the progression of neurodegenerative diseases, in part because translation from animal models to the clinic has been hampered by poor distribution to the brain. The present studies examined a selected series of para-phenyl–substituted diindolylmethane (C-DIM) compounds that display anti-inflammatory and neuroprotective efficacy in vitro. We postulated that the pharmacokinetic behavior of C-DIM compounds after oral administration would correlate with neuroprotective efficacy in vivo in a mouse model of Parkinson’s disease. Pharmacokinetics and metabolism of 1,1-bis(3′-indolyl)-1-(p-methoxyphenyl)methane (C-DIM5), 1,1-bis(3′-indolyl)-1-(phenyl)methane, 1,1-bis(3′-indolyl)-1-(p-hydroxyphenyl)methane (C-DIM8), and 1,1-bis(3′-indolyl)-1-(p-chlorophenyl)methane (C-DIM12) were determined in plasma and brain of C57Bl/6 mice after oral and intravenous administration at 10 and 1 mg/Kg, respectively. Putative metabolites were measured in plasma, liver, and urine. C-DIM compounds given orally displayed the highest area under the curve, Cmax, and Tmax levels, and C-DIM12 exhibited the most favorable pharmacokinetics of the compounds tested. Oral bioavailability of each compound ranged from 6% (C-DIM8) to 42% (C-DIM12). After pharmacokinetic studies, the neuroprotective efficacy of C-DIM5, C-DIM8, and C-DIM12 (50 mg/Kg per oral) was examined in mice exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and probenecid for 14 days, a model of progressive neurodegeneration with a strong neuroinflammatory component. C-DIM5 and C-DIM12 given orally once daily after one week of exposure to MPTP and probenecid prevented further loss of dopaminergic neurons in the substantia nigra pars compacta and striatal dopamine terminals, indicating that these compounds could be effective therapeutic agents to prevent neurodegeneration.
Producción y calidad nutrimental de forrajes en condiciones del Trópico Húmedo de México* Production and nutritional quality of forages in conditions Humid Tropics of Mexico

In aim to determine the nutritional quality of forages in a production system of dual purpose bovines in southeastern Mexico, forage samples were taken using exclusion cages and forage available in the meadow by Hand Plucking to determine: content crude protein (PC), neutral detergent fiber (FDN), acid detergent fiber (FDA) and the minerals copper (Cu), iron (Fe), zinc (Zn), calcium (Ca), magnesium (Mg), sodium (Na ), potassium (K) and phosphorus (P) in five cattle ranches in the humid tropics of Chiapas, throughout the year. The data analysis considered the fixed effects ranch month of the year, time of year, forage species and sampling technique used. There were differences ( p< 0.05) between seasons ranches and content PC, FDN, FDA and between ranches in mineral content; there were differences ( p< 0.05) between the months of the year and between forage species in the content of FDN and FDA, and differences ( p< 0.05) in the contents of PC, FDN, FDA, Cu, Zn, Mg, Na and K between sampling techniques used. It is concluded that the nutritional quality of forages is affected by the season, being the rainy season and norths where there is the greatest FDN, but with lower contents of PC and FDA. The 100, 28 and 72% of samples of fodder had values below the minimum
Pyrosequencing cut‐off value identifying BRAFV600E mutation in fine needle aspiration samples of thyroid nodules

Context Recently, tremendous efforts have been made towards the development of sensitive techniques to detect the BRAFV600E mutation in fine needle aspiration biopsy (FNAB) samples. However, newly developed quantitative and semi‐quantitative methods, such as dual‐priming oligonucleotide (DPO)‐based multiplex polymerase chain reaction (PCR), have the potential to generate false‐positive (FP) results.
Diversifying Selection in Human Papillomavirus Type 16 Lineages Based on Complete Genome Analyses

ABSTRACT Human papillomavirus type 16 (HPV16) is the primary etiological agent of cervical cancer, the second most common cancer in women worldwide. Complete genomes of 12 isolates representing the major lineages of HPV16 were cloned and sequenced from cervicovaginal cells. The sequence variations within the open reading frames (ORFs) and noncoding regions were identified and compared with the HPV16R reference sequence (50). This whole-genome approach gives us unprecedented precision in detailing sequence-level changes that are under selection on a whole-viral-genome scale. Of 7,908 base pair nucleotide positions, 313 (4.0%) were variable. Within the 2,452 amino acids (aa) comprising 8 ORFs, 243 (9.9%) amino acid positions were variable. In order to investigate the molecular evolution of HPV16 variants, maximum likelihood models of codon substitution were used to identify lineages and amino acid sites under selective pressure. Five codon sites in the E5 (aa 48, 65) and E6 (aa 10, 14, 83) ORFs were demonstrated to be under diversifying selective pressure. The E5 ORF had the overall highest nonsynonymous/synonymous substitution rate (ω) ratio (M3 = 0.7965). The E2 gene had the next-highest ω ratio (M3 = 0.5611); however, no specific codons were under positive selection. These data indicate that the E6 and E5 ORFs are evolving under positive Darwinian selection and have done so in a relatively short time period. Whether response to selective pressure upon the E5 and E6 ORFs contributes to the biological success of HPV16, its specific biological niche, and/or its oncogenic potential remains to be established.
Secretogranins I and II: two tyrosine-sulfated secretory proteins common to a variety of cells secreting peptides by the regulated pathway

We report on the biochemical and immunological properties as well as on the cellular and subcellular distribution of two proteins, called secretogranins I and II. These proteins specifically occur in a wide variety of endocrine and neuronal cells that package and sort regulatory peptides into secretory granules. Both secretogranins take the same intracellular route as the peptides and are also sorted into secretory granules. Secretogranins I and II are biochemically and immunologically distinct proteins and differ from chromogranin A. Yet, these three proteins are similar to each other in many respects and therefore constitute one class of proteins. A remarkable feature of this protein class is a very acidic pI, brought about by a high content of acidic amino acids as well as by phosphorylation on serine and sulfation on tyrosine and O-linked carbohydrate. As a result, this class of proteins has a high net negative charge even at the acidic pH of the trans Golgi cisternae. We discuss the possibility that this property of the proteins may point to a role in the packaging of regulatory peptides into secretory granules.
Cluster-Randomized Clinical Trial Examining the Impact of Platelet Function Testing on Practice: The Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome Prospective Open Label Antiplatelet Therapy Study

Background—Little is known about how clinicians use platelet function testing to guide choice and dosing of adenosine diphosphate receptor inhibitor (ADPri) therapy in routine community practice. Methods and Results—The Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (ACS)—Prospective, Open Label, Antiplatelet Therapy Study (TRANSLATE-POPS) was a cluster-randomized trial in which 100 hospitals were assigned access to no-cost platelet function testing versus usual care for acute myocardial infarction patients treated with percutaneous coronary intervention. In both arms, ADPri treatment decisions were left up to the care team. The primary end point was the frequency of ADPri therapy adjustment before discharge. Secondary end points included 30-day rates of major adverse cardiovascular events and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries–defined bleeding events. Platelet function testing was performed in 66.9% of patients treated in intervention sites versus 1.4% of patients in usual care sites. Intervention arm patients were more likely to have ADPri therapy adjustment than usual care patients (14.8% versus 10.5%, P=0.004; odds ratio 1.68, 95% confidence interval 1.18–2.40); however, there were no significant differences in 30-day major adverse cardiovascular events (4.8% versus 5.4%, P=0.73; odds ratio 0.94, 95% confidence interval 0.66–1.34) or bleeding (4.3% versus 4.2%, P=0.33; odds ratio 0.86, 95% confidence interval 0.55–1.34). One-year outcomes were also not significantly different between groups. An as-treated analysis showed higher incidence of ADPri therapy adjustment among intervention arm patients who received platelet function testing than untested usual care arm (16.4% versus 10.2%, P<0.0001), but no significant differences in major adverse cardiovascular events or bleeding. Conclusions—TRANSLATE-POPS found that when clinicians routinely used platelet function testing, they were more likely to adjust their choice or dosing of ADPri therapy; yet with few changes in therapy overall, significant differences in clinical outcomes were not seen. Clinical Trial Registration—URL: http://www.clinicaltrials. gov. Unique identifier: NCT01088503.
The impact of PACS on clinician work practices in the intensive care unit: a systematic review of the literature

Objective To assess evidence of the impact of Picture Archiving and Communication Systems (PACS) on clinicians' work practices in the intensive care unit (ICU). Methods We searched Medline, Pre-Medline, CINAHL, Embase, and the SPIE Digital Library databases for English-language publications between 1980 and September 2010 using Medical Subject Headings terms and keywords. Results Eleven studies from the USA and UK were included. All studies measured aspects of time associated with the introduction of PACS, namely the availability of images, the time a physician took to review an image, and changes in viewing patterns. Seven studies examined the impact on clinical decision-making, with the majority measuring the time to image-based clinical action. The effect of PACS on communication modes was reported in five studies. Discussion PACS can impact on clinician work practices in three main areas. Most of the evidence suggests an improvement in the efficiency of work practices. Quick image availability can impact on work associated with clinical decision-making, although the results were inconsistent. PACS can change communication practices, particularly between the ICU and radiology; however, the evidence base is insufficient to draw firm conclusions in this area. Conclusion The potential for PACS to impact positively on clinician work practices in the ICU and improve patient care is great. However, the evidence base is limited and does not reflect aspects of contemporary PACS technology. Performance measures developed in previous studies remain relevant, with much left to investigate to understand how PACS can support new and improved ways of delivering care in the intensive care setting.
Spectra of Stimulated Emission in the Hydrogen-Fluorine Reaction Process and Energy Transfer from DF to CO(2).

The spectra of stimulated emission, observed in the process of the H(2) + F(2) ? HF and D(2) + F(2) F(2)? DF reactions, were investigated and compared. The stimulated emission in the vibrational transitions up to 6-5 for the HF molecule and up to 9-8 for the DF molecule was discovered. It was found that the emission energy in the transitions of 2-1 and 5-4 bands in the H(2) + F(2) mixture was the highest possible. In the D(2) + F(2) mixture the emission energy maxima correspond to the 3-2 and 8-7 bands. The presence of the two maxima reflects the fact that the two types of chemical reactions contribute to the population inversion creation. One is a F + H(2)(D(2)) reaction, the other is a H(D) + F(2) reaction. By analyzing the characteristics of the chemical laser in which the energy exchange between the DF and CO(2) molecules takes place, the energy-transfer rate constant was estimated with the value being equal to (1.5 +/- 0.5) x 10(-12) cm(3) sec(-1).
Macroeconomics: A Survey of Laboratory Research

This chapter surveys laboratory experiments addressing macroeconomic phenomena. The first part focuses on experimental tests of the microfoundations of macroeconomic models discussing laboratory studies of intertemporal consumption/savings decisions, time (in)consistency of preferences and rational expectations. Part two explores coordination problems of interest to macroeconomists and mechanisms for resolving these problems. Part three looks at experiments in specific macroeconomic sectors including monetary economics, labor economics, international economics as well-as large scale, multi-sector models that combine several sectors simultaneously. The final section addresses experimental tests of macroeconomic policy issues.
Measurement of Glutathionylated Haemoglobin by MAL-DI-ToF Mass Spectrometry as a Biomarker of Oxidative Stress in Heavy Smokers and in Occupational Obese Subjects

Glutathionyl-haemoglobin (Hb-SSG) is a minor form of haemoglobin characterized by the presence of a disulfide bond between the β-93 cysteine residue and the thiol group of glutathione. Hb-SSG is naturally present in the erythrocytes at levels comparable to those of glycated haemoglobin and can be measured by MALDI mass spectrometry on very small samples of erythrocytes from peripheral blood. Since Hb-SSG has been recognized as a sensitive biomarker of oxidative stress in several degenerative diseases (diabetes, hyperlipidemia, kidney disease) and in healthy workers exposed to glutathione-depleting toxic agents such as butadiene, we have measured for the first time the levels of Hb-SSG in two groups: healthy heavy cigarette smokers and overweight-obese. For both classes of subjects, the measured levels (6.4%±1.7%, n=30 for smokers; 3.0%±0.8%, n=20 for overweight-obese) are in the upper 97thpercentile of those measured in the Italian general population. Levels in smokers show a small, yet statistically significant dependence on the level of smoking addiction (>20 cig./day vs. ￡20 cig./day: 7.0% ± 1.4% vs. 5.7% ± 1.1%; p < 0.05). This biomarker thus adds to those presently available to rationally assess the extent of biological damage caused by tobacco smoking.
Emotional Intelligence: What Does the Research Really Indicate?

In her critique of emotional intelligence (EI) theory and research, Waterhouse (2006) makes several claims. First, she argues that there are "many conflicting constructs of EI," implying that it cannot be a valid concept given this multiplicity of views. Second, she cites some research and opinion suggesting that "EI has not been differentiated from personality plus IQ. " Third, she states that "the claim that EI determines real-world success has not been validated. " Finally, she proposes that research on brain function proves that there cannot be a "unitary EI. " Based on this critique, she argues that EI competencies should not be taught in the schools. This article addresses each of these criticisms and shows that there now is much more empirical support for EI theory than Waterhouse suggested in her article.
Evolutionary biology of starvation resistance: what we have learned from Drosophila

Most animals face periods of food shortage and are thus expected to evolve adaptations enhancing starvation resistance (SR). Most of our knowledge of the genetic and physiological bases of those adaptations, their evolutionary correlates and trade‐offs, and patterns of within‐ and among‐population variation, comes from studies on Drosophila. In this review, we attempt to synthesize the various facets of evolutionary biology of SR emerging from those studies. Heritable variation for SR is ubiquitous in Drosophila populations, allowing for large responses to experimental selection. Individual flies can also inducibly increase their SR in response to mild nutritional stress (dietary restriction). Both the evolutionary change and the physiological plasticity involve increased accumulation of lipids, changes in carbohydrate and lipid metabolism and reduction in reproduction. They are also typically associated with greater resistance to desiccation and oxidative stress, and with prolonged development and lifespan. These responses are increasingly seen as facets of a shift of the physiology towards a ‘survival mode’, which helps the animal to survive hard times. The last decade has seen a great progress in revealing the molecular bases of induced responses to starvation, and the first genes contributing to genetic variation in SR have been identified. In contrast, little progress has been made in understanding the ecological significance of SR in Drosophila; in particular it remains unclear to what extent geographical variation in SR reflect differences in natural selection acting on this trait rather than correlated responses to selection on other traits. Drosophila offers a unique opportunity for an integrated study of the manifold aspects of adaptation to nutritional stress. Given that at least some major molecular mechanisms of response to nutritional stress seem common to animals, the insights from Drosophila are likely to apply more generally than just to dipterans or insects.
Pharmacodynamics of taxol in human head and neck tumors.

The pharmacodynamics of taxol in human head and neck squamous cell carcinoma were studied using histocultures of surgical specimens from patients (n = 22). Tumors were treated with taxol for 24 h. The inhibition of DNA synthesis was determined by 48 h cumulative bromodexyuridine (BrdUrd) incorporation. The induction of apoptosis was measured by morphological changes, in situ DNA end labeling, post-exonuclease III BrdUrd labeling, and DNA fragmentation. Inhibition of the BrdUrd labeling index (LI) by taxol was incomplete, with 11 tumors showing maximal inhibition (Emax) of 30-50% and the remaining 11 tumors showing and Emax of 50-80%. For both groups, the inhibition approached maximum values at 1 microM taxol concentration; an additional 10-fold increase in drug concentrations did not significantly enhance the inhibition. The taxol concentrations required for a 30% inhibition (IC30) were 4.2 and 0.3 microM for the first and second groups, respectively. The IC30 correlated with the Emax (r2 = 0.39; P < 0.001). Taxol induced apoptosis in all tumors, 11 tumors showed a maximal fraction of apoptotic tumor cells between 3 and 10% and 11 tumors between 13 and 28%, whereas untreated controls showed a maximal apoptotic index of < 1%. For individual tumors, the maximal apoptotic index occurred between 0.1 and 3 microM, and correlated with the BrdUrd LI for the untreated control (r2 = 0.37; P < 0.01). It is interesting that > 95% of apoptotic cells were BrdUrd labeled, whereas not all BrdUrd-labeled cells were apoptotic. To investigate the basis of the variable tumor response to taxol, we determined the expression of multidrug resistance P-glycoprotein (Pgp), p53, and bcl-2 proteins, using immunohistochemical staining and Western blot analysis. Eleven (50%), 10 (45%), and 7 (32%) tumors expressed Pgp, p53, and bcl-2, respectively. Patients with Pgp-positive tumors showed a higher number of affected lymph nodes than those with Pgp-negative tumors (P < 0.05). Compared with moderately and well differentiated tumors, the poorly differentiated tumors expressed p53 and Pgp more frequently and showed a lower maximum inhibition of DNA synthesis and a higher apoptotic fraction after taxol treatment (P < 0.05 in both cases). Pgp expression correlated differently with taxol-induced inhibition of DNA synthesis than with apoptosis; Pgp-positive tumors showed a significantly higher Emax (63%) and IC30 (4.2 microM) but also a higher apoptotic index (17%) than Pgp-negative tumors (Emax 36%; IC30, 0.3 microM; and apoptotic index; 6%; P < 0.05 for all cases). p53 and bcl-2 expression did not correlated with taxol-induced inhibition of DNA synthesis or apoptosis. The data indicate that taxol acts through apoptosis and inhibition of proliferation in human head and neck cancer. Pgp overexpression appears to protect cells from the antiproliferative effect of taxol but correlated with a higher apoptosis.
Efficacy of Various Percutaneous Interventions for In-Stent Restenosis: Comprehensive Network Meta-Analysis of Randomized Controlled Trials

Background—In-stent restenosis (ISR) remains a difficult problem in interventional cardiology. The relative efficacy and safety of available interventions is not clear. We aimed to perform a network meta-analysis using both direct evidence and indirect evidence to compare all available interventions. Methods and Results—We systematically searched electronic databases for randomized trials comparing ≥2 treatments for ISR. A network meta-analysis was performed using a Bayesian approach. Eleven treatments were compared in 31 studies with 8157 patient-years follow-up. Compared with balloon angioplasty, everolimus-eluting stent (hazard ratio [95% credibility interval], 0.13 [0.048–0.35]), paclitaxel-eluting balloon (0.32 [0.20–0.49]), paclitaxel-eluting cutting balloon (0.054 [0.0017–0.5]), paclitaxel-eluting stent (0.39 [0.24–0.62]), and sirolimus-eluting stent (0.32 [0.18–0.50]) are associated with lower target vessel revascularization. Balloon angioplasty is not different from cutting balloon (0.73 [0.31–1.5]), excimer laser (0.89 [0.29–2.7]), rotational atherectomy (0.96 [0.53–1.7]), and vascular brachytherapy (0.60 [0.35–1.0]). In drug-eluting stent ISR, balloon angioplasty was inferior to everolimus-eluting stent (0.19 [0.049–0.76]), paclitaxel-eluting balloon (0.43 [0.18–0.80]), paclitaxel-eluting stent (0.35 [0.13–0.76]), and sirolimus-eluting stent (0.36 [0.11–0.86]) for target vessel revascularization. There was no difference between treatments in probable or definitive stent thrombosis. The results of binary restenosis and target lesion revascularization were similar. Paclitaxel-eluting cutting balloon, everolimus-eluting stent, and paclitaxel-eluting balloon have the highest probability of being in the top 3 treatments based on low target lesion revascularization, but there was no statistical significant difference between them. Conclusions—Balloon angioplasty is inferior to all drug-eluting treatments for ISR, including drug-eluting stent ISR. Drug-eluting stent, particularly everolimus-eluting stent, or paclitaxel-eluting cutting balloon and paclitaxel-eluting balloon should be preferred for treating ISR.