Miracle-dz/UniFAR-FTUs huggingface dataset:
Protective role of silymarin against manganese‐induced nephrotoxicity and oxidative stress in rat

Metal toxicity may occur after exposure from many sources. Oxidative stress is thought to be involved in manganese‐induced toxicity and leads to various health disorders. Silymarin (SIL), a natural flavonoid, has been reported to have many benefits and medicinal properties. The aim of this study was to assess the toxicity of manganese (Mn) on oxidative stress and DNA damage in the kidney of rats and its alleviation by SIL. Manganese was given orally in drinking water (20 mg MnCl2/mL) with or without SIL administration (100 mg /kg intraperitoneally) for 30 days. Our data showed that SIL significantly prevented Mn induced nephrotoxicity, indicated by both diagnostic indicators of kidney injury like plasma urea, uric acid and creatinine and urinary electrolyte levels and by histopathological analysis. Moreover, Mn‐induced profound elevation of the production of reactive oxygen species (ROS) and altered the levels of oxidative stress related biomarkers in kidney tissue. This is evidenced by the increase of lipid peroxidation, protein carbonylation, DNA fragmentation and urinary hydrogen peroxide, while, the activities of enzymatic antioxidant and glutathione level were decreased. Treatment with SIL reduced the alterations in the renal and urine markers, decreasing lipid peroxidation markers, increasing the antioxidant cascade and decreasing the Mn‐induced damage. All these changes were supported by histopathological observations. These findings suggested that the inhibition of Mn‐induced damage by SIL was due at least in part to its antioxidant activity and its capacity to modulate the oxidative damage. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1147–1154, 2014.
Anticonvulsant drugs and bone metabolism

Abstract The influence of chronic antiepileptic treatment on bone metabolism has been investigated in 52 adult epileptics, who had normal dietary intake, sunlight exposure and daily living activities. None of the patients had symptoms or signs suggestive of osteomalacia. Serum phosphate levels were significantly decreased and serum alkaline phosphatase levels were significantly increased in the patients compared with matched controls. Calcitonin values and bone mineral content, measured by single photon absorptiometry, were significantly lower among anticonvulsant users. Calcium metabolism impairment grossly correlated to the number of drugs concurrently used by the patient but not to the types, to the relative plasma concentrations or to the overall duration of the treatment. Our findings indicate that in ambulatory patients with adequate diet and outdoor activities in Italy present with clinically irrelevant impairment of bone metabolism.
Phenological investigations of different winter-deciduous species growing under Mediterranean conditions

Phenological stages are the result of biorhythms and environmental factors, these last are probably the same ones that caused, during evolution, adjustments of the species to different climate. The present study was carried out in a Phenological Garden located in central Italy (Perugia, Umbria Region) which contains indicator species, common to all International Phenological Gardens. The aim of this study was to determine and analyse the average trends of development of eight plant species and their phenological adjustment to the Mediterranean environment, over a nine-year period (1997–2005). The results of the statistical analyses show a strong relationship between the temperature trends and vegetative seasonal evolutions interpreted by phenological data for all the species considered. Moreover, it was demonstrated that the plants studied may approach or close completely the timing gaps eventually created during the first phenological phases, adjusting thus the beginning of subsequent phenophases. RésuméLes stades phénologiques résultent des biorythmes et des facteurs environnementaux qui sont probablement ceux là même qui ont provoqué les changements d’aires de répartition des espèces pendant leur évolution, en réponse aux changements climatiques. La présente étude a été réalisée dans un Jardin phénologique situé dans le centre de l’Italie (Perugia, Ombrie) où l’on trouve des espèces indicatrices communes à tous les Jardins phénologiques internationaux. Le but de cette étude a été de déterminer et d’analyser les tendances moyennes de développement de huit espèces de plantes et leur ajustement phénologique à l’environnement méditerranéen, dans une période de neuf ans (1997–2005). Les résultats des analyses statistiques montrent une forte corrélation entre les tendances des températures et le développement végétatif saisonnier, pour toutes les espèces étudiées. On a également démontré que les plantes étudiées peuvent réduire ou éliminer les décalages temporels entre les premières phases phénologiques, en ajustant le début des phénophases suivantes.
Molecular epidemiology of human metapneumovirus in Ireland

Human metapneumovirus (hMPV) is a cause of respiratory illness ranging from wheezing to bronchiolitis and pneumonia in children. A quantitative real‐time reverse‐transcriptase polymerase chain reaction (RT‐PCR) assay was developed for the detection of all four main genetic lineages of hMPV and employed to validate an indirect immunofluorescence (IF) assay to detect hMPV positive specimens. The IF assay detected 24 positives from a screen of 625 randomly selected pediatric respiratory specimens collected (3.8% prevalence). From this cohort of 625 specimens, 229 were also tested by real‐time RT‐PCR assay. This included the 24 IF positive specimens and 205 randomly selected specimens from both study periods. In addition to confirming all the IF positives, the real‐time assay detected an additional six hMPV positive specimens giving rise to a combined prevalence of 4.8%. Phylogenetic analysis showed that hMPV subtypes A2b and B2 to be the most prevalent genotypes circulating in our population and surprisingly no hMPV subgroups A1 or B1 were detected during this study period. Based on this phylogenetic analysis, we propose the existence of sub‐clusters of hMPV genotype B2 present in our population which we term subtypes B2a and B2b. The mean log 10 copies/ml of quantitative RT‐PCR determinations from these 30 hMPV positive respiratory specimens was 6.35 (range = 4.44–8.15). Statistical analysis of quantitative RT‐PCR determinations of viral load from these 30 respiratory specimens suggests that hMPV genotype B specimens have a higher viral load than hMPV genotype A isolates (P < 0.03). J. Med. Virol. 80:510–516, 2008. © 2008 Wiley‐Liss, Inc.
A Role for Host Phosphoinositide 3-Kinase and Cytoskeletal Remodeling during Cryptosporidium parvumInfection

ABSTRACT Cryptosporidium parvum preferentially infects epithelial cells lining the intestinal mucosa of mammalian hosts. Parasite development and propagation occurs within a unique intracellular but extracytoplasmic parasitophorous vacuole at the apical surface of infected cells. Parasite-induced host cell signaling events and subsequent cytoskeletal remodeling were investigated by using cultured bovine fallopian tube epithelial (BFTE) cells inoculated with C. parvum sporozoites. Indirect-immunofluorescence microscopy detected host tyrosine phosphorylation within 30 s of inoculation. At >30 min postinoculation, actin aggregates were detected at the site of parasite attachment by fluorescein isothiocyanate-conjugated phalloidin staining as well as by indirect immunolabeling with monoclonal anti-actin. The actin-binding protein villin was also detected in focal aggregates at the site of attachment. Host cytoskeletal rearrangement persisted for the duration of the parasitophorous vacuole and contributed to the formation of long, branched microvilli clustered around the cryptosporidial vacuole. The phosphoinositide 3-kinase inhibitor wortmannin significantly inhibited (P < 0.05)C. parvum infection when BFTE cells were pretreated for 60 min at 37°C prior to inoculation. Similarly, treatment of BFTE cells with the protein kinase inhibitors genistein and staurosporine and the cytoskeletally acting compounds 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazapine, cytochalasin D, and 2,3-butanedione monoxime significantly inhibited (P < 0.05) in vitro infection at 24 h postinoculation. These findings demonstrate a prominent role for phosphoinositide 3-kinase activity during the early C. parvum infection process and suggest that manipulation of host signaling pathways results in actin rearrangement at the site of sporozoite attachment.
Cognitive profiles of autopsy-confirmed Lewy body variant vs pure Alzheimer disease.

OBJECTIVE To compare the cognitive profiles of patients with autopsy-confirmed Alzheimer disease (AD), with or without concomitant Lewy bodies, on 2 dementia screening measures. METHODS Profiles on subtests of the Mattis Dementia Rating Scale (range, 105-125) and of component items of the Mini-Mental State Examination were compared between 23 patients with uncomplicated AD and 23 patients with concomitant AD and Lewy body pathology (Lewy body variant [LBV]). RESULTS Although the groups did not differ significantly regarding age, years of education, total Mini-Mental State Examination score, or total Mattis Dementia Rating Scale score, the AD group performed significantly worse than the LBV group on the Mattis Dementia Rating Scale Memory subscale (P < .005). In contrast, the LBV group demonstrated poorer performance than the pure AD group on the Initiation/Perseveration subscale (P < .02). The groups did not differ significantly on the Attention, Construction, or Conceptualization subscales. The same overall pattern of results was obtained when subgroups with mild to moderate and moderate to severe dementia were examined separately, with the additional finding that in the mild-to-moderate range patients with dementia and LBV performed worse than patients with pure AD on the Construction subscale. CONCLUSIONS The difference in pattern of cognitive deficits among patients with pure AD vs those with AD and LBV is similar to that seen between AD and more subcortical/frontal dementias (eg, Huntington disease) This suggests that the concomitant Lewy body pathology significantly contributes to the presentation of the cognitive dysfunction in individuals with LBV.
Efficacy and safety of ixekizumab treatment in Japanese patients with moderate‐to‐severe plaque psoriasis: Subgroup analysis of a placebo‐controlled, phase 3 study (UNCOVER‐1)

The present study describes a subgroup analysis of 33 Japanese patients participating in UNCOVER‐1, an international, placebo‐controlled, phase 3 study of ixekizumab in patients with moderate‐to‐severe psoriasis. Patients were randomized to a placebo (n = 13) or ixekizumab 80 mg every 4 (IXEQ4W, n = 12) or 2 (IXEQ2W, n = 8) weeks, from week 0–12. At week 12, ixekizumab‐treated patients with a static Physician Global Assessment score 0 or 1 (sPGA [0,1]; n = 16) were re‐randomized to a placebo (n = 6), ixekizumab 80 mg every 12 (IXEQ12W, n = 5) or 4 (IXEQ4W, n = 5) weeks, from week 12–60. At week 12, more ixekizumab‐treated versus placebo‐treated patients achieved sPGA (0,1) (≥66.7% vs 0%), ≥75% improvement in Psoriasis Area and Severity Index (≥75% vs 0%), and sPGA (0) or 100% improvement in Psoriasis Area and Severity Index (both ≥33.3% vs 0%), with improved symptoms and quality of life. At week 60, 100% (IXEQ4W), 40.0% (IXEQ12W) and 16.7% (placebo) had maintained sPGA (0,1). From week 0–12, treatment‐emergent adverse events were 76.9% (placebo), 75.0% (IXEQ4W) and 87.5% (IXEQ2W), and from week 12–60 were 66.7% (placebo) and 100% (IXEQ12W, IXEQ4W). Ixekizumab‐treated patients had no severe treatment‐emergent adverse events, and one serious TEAE (IXEQ4W); infection was the most frequent treatment‐emergent adverse event. In conclusion, ixekizumab for 60 weeks was effective and safe for Japanese patients with moderate‐to‐severe psoriasis, in line with the overall findings from UNCOVER‐1.
Hospital survey on patient safety culture: psychometric analysis on a Scottish sample

Objective To investigate the psychometric properties of the Hospital Survey on Patient Safety Culture on a Scottish NHS data set. Methods The data were collected from 1969 clinical staff (estimated 22% response rate) from one acute hospital from each of seven Scottish Health boards. Using a split-half validation technique, the data were randomly split; an exploratory factor analysis was conducted on the calibration data set, and confirmatory factor analyses were conducted on the validation data set to investigate and check the original US model fit in a Scottish sample. Results Following the split-half validation technique, exploratory factor analysis results showed a 10-factor optimal measurement model. The confirmatory factor analyses were then performed to compare the model fit of two competing models (10-factor alternative model vs 12-factor original model). An S–B scaled χ2 square difference test demonstrated that the original 12-factor model performed significantly better in a Scottish sample. Furthermore, reliability analyses of each component yielded satisfactory results. The mean scores on the climate dimensions in the Scottish sample were comparable with those found in other European countries. Conclusions This study provided evidence that the original 12-factor structure of the Hospital Survey on Patient Safety Culture scale has been replicated in this Scottish sample. Therefore, no modifications are required to the original 12-factor model, which is suggested for use, since it would allow researchers the possibility of cross-national comparisons.
In situ endothelialization of intravascular stents from progenitor stem cells coated with nanocomposite and functionalized biomolecules

Owing to their noninvasive nature, coronary artery stents have become popular demand for patients undergoing percutaneous coronary intervention. Late restenosis, in‐stent restenosis, and late thrombosis, all mediated by the denuded endothelium, represent the most recurrent failures of vascular stent induction. Higher patency rates of stents can be achieved by restoring the native internal environment of the vessel—an endothelium monolayer. This active organ inhibits the inflammatory reaction to injury responsible for thrombus and intimal hyperplasia, thereby providing a novel therapeutic option to combat the unacceptably high prevalence of restenosis. As the climax of the nanotechnology era approaches, tissue engineering is being explored by means of exploiting the multipotent abilities of stem cells and their adherence to bioactive surface nanocomposite polymers. The endothelium can be reconstructed from neighboring intact endothelium and adherence of circulating endothelium progenitor cells. The latter takes place via a series of signaling events: mobilization, adhesion, chemoattraction, migration, proliferation, and finally their differentiation in mature endothelial cells. A nanotopography surface can orchestrate endothelium formation, attributable to cellular interactions promoted by its nanosize. This review encompasses the prospect of in situ endothelialization, the mechanisms regulating the process, and the advantages of using a new generation of bioactive nanocomposite materials for coating metal stent scaffolds.
Kinetics and Yields of Pesticide Biodegradation at Low Substrate Concentrations and under Conditions Restricting Assimilable Organic Carbon

ABSTRACT The fundamentals of growth-linked biodegradation occurring at low substrate concentrations are poorly understood. Substrate utilization kinetics and microbial growth yields are two critically important process parameters that can be influenced by low substrate concentrations. Standard biodegradation tests aimed at measuring these parameters generally ignore the ubiquitous occurrence of assimilable organic carbon (AOC) in experimental systems which can be present at concentrations exceeding the concentration of the target substrate. The occurrence of AOC effectively makes biodegradation assays conducted at low substrate concentrations mixed-substrate assays, which can have profound effects on observed substrate utilization kinetics and microbial growth yields. In this work, we introduce a novel methodology for investigating biodegradation at low concentrations by restricting AOC in our experiments. We modified an existing method designed to measure trace concentrations of AOC in water samples and applied it to systems in which pure bacterial strains were growing on pesticide substrates between 0.01 and 50 mg liter−1. We simultaneously measured substrate concentrations by means of high-performance liquid chromatography with UV detection (HPLC-UV) or mass spectrometry (MS) and cell densities by means of flow cytometry. Our data demonstrate that substrate utilization kinetic parameters estimated from high-concentration experiments can be used to predict substrate utilization at low concentrations under AOC-restricted conditions. Further, restricting AOC in our experiments enabled accurate and direct measurement of microbial growth yields at environmentally relevant concentrations for the first time. These are critical measurements for evaluating the degradation potential of natural or engineered remediation systems. Our work provides novel insights into the kinetics of biodegradation processes and growth yields at low substrate concentrations.
IL-32 is a molecular marker of a host defense network in human tuberculosis

IL-32 links the microbicidal peptide pathway with resistance to disease progression in clinical tuberculosis. TB Sunny Side Up Interleukin-32 (IL-32) could be a correlate of protection against tuberculosis. Montoya et al. report that IL-32 is a potential candidate marker of host defense against tuberculosis. Mycobacterium tuberculosis causes a sometimes deadly infection that nonetheless only develops to disease in about 10% of individuals. The authors performed gene expression profiles of human macrophages and found an association between IL-32 and the vitamin D antimicrobial pathway. Moreover, analysis of five different clinical data sets suggested that IL-32 can serve as a molecular marker of latent tuberculosis and may be activated in response to signaling by IL-15. These data suggest that IL-32 may not only serve as a putative correlate of protection but also contribute directly to host response to tuberculosis. Tuberculosis is a leading cause of infectious disease–related death worldwide; however, only 10% of people infected with Mycobacterium tuberculosis develop disease. Factors that contribute to protection could prove to be promising targets for M. tuberculosis therapies. Analysis of peripheral blood gene expression profiles of active tuberculosis patients has identified correlates of risk for disease or pathogenesis. We sought to identify potential human candidate markers of host defense by studying gene expression profiles of macrophages, cells that, upon infection by M. tuberculosis, can mount an antimicrobial response. Weighted gene coexpression network analysis revealed an association between the cytokine interleukin-32 (IL-32) and the vitamin D antimicrobial pathway in a network of interferon-γ– and IL-15–induced “defense response” genes. IL-32 induced the vitamin D–dependent antimicrobial peptides cathelicidin and DEFB4 and to generate antimicrobial activity in vitro, dependent on the presence of adequate 25-hydroxyvitamin D. In addition, the IL-15–induced defense response macrophage gene network was integrated with ranked pairwise comparisons of gene expression from five different clinical data sets of latent compared with active tuberculosis or healthy controls and a coexpression network derived from gene expression in patients with tuberculosis undergoing chemotherapy. Together, these analyses identified eight common genes, including IL-32, as molecular markers of latent tuberculosis and the IL-15–induced gene network. As maintaining M. tuberculosis in a latent state and preventing transition to active disease may represent a form of host resistance, these results identify IL-32 as one functional marker and potential correlate of protection against active tuberculosis.
Pattern recognition based forearm motion classification for patients with chronic hemiparesis

To make full use of electromyography (EMG) that contains rich information of muscular activities in active rehabilitation for motor hemiparetic patients, a couple of recent studies have explored the feasibility of applying pattern recognition technique to the classification of multiple motion classes for stroke survivors and reported some promising results. However, it still remains unclear if kinematics signals could also bring good motion classification performance, particularly for patients after traumatic brain damage. In this study, the kinematics signals was used for motion classification analysis in three stroke survivors and two patients after traumatic brain injury, and compared with EMG. The results showed that an average classification error of 7.9±6.8% for the affected arm over all subjects could be achieved with a linear classifier when they performed multiple fine movements, 7.9% lower than that when using EMG. With either kind of signals, the motor control ability of the affected arm degraded significantly in comparison to the intact side. The preliminary results suggested the great promise of kinematics information as well as the biological signals in detecting user's conscious effort for robot-aided active rehabilitation.
History dependence of protein adsorption kinetics

The behavior of proteins at biological and synthetic interfaces is often characterized by a strong history dependence caused by long relaxation times or irreversible transitions. In this work, we introduce the rate of adsorption as a means to systematically quantify the extent, and identify the underlying causes, of history dependence. We use multistep kinetic experiments in which the i′th step is an exposure of a Si(Ti)O2 surface to a flowing fibronectin or cytochrome c solution of concentration ci for a time ti (ci = 0 corresponds to a rinse) and measure the protein adsorption by optical waveguide light mode spectroscopy. The rate of adsorption is sensitive to the structure of the adsorbed layer, and we observe it to greatly increase, for a given adsorbed density, when going from a first to a subsequent adsorption step. This increase is most pronounced when the duration of the initial adsorption step is long. We attribute these observations to the gradual and irreversible formation of protein clusters or locally ordered structures and use them to explain previous underestimates of kinetic data by mesoscopic model descriptions. A thorough understanding of these complex postadsorption events, and their impact on history dependence, is essential for many physiological and biotechnological processes. Optical waveguide lightmode spectroscopy is a promising technique for their macroscopic quantification.