Miracle-dz/UniFAR-FTUs huggingface dataset:
For Debate: May the Use of the Polyene Macrolide Natamycin as a Food Additive Foster Emergence of Polyene-Resistance in Candida Species?

Natamycin is approved almost worldwide as a food additive for surface treatment of cheese and sausages. Its use is considered to be safe as Natamycin is extremely sensitive to ultraviolet light and an acidic pH, so that products exposed to light in the retail industry and food stores are likely free from Natamycin. However, the use of an acid-, heat- and light stable Natamycin formulation in yoghurt has recently been authorized in the USA as well as in Australia and New Zealand. Furthermore, yoghurt is stored in sealed cups in refrigerated shelves, so it will not be exposed to light and thus not be inactivated during storage. Consequently, the resident flora will be exposed to Natamycin and it may exert a resistance selective pressure on faecal Candida spp. hypothetically selecting strains being resistant to Amphothericin B. In this review literature has been evaluated addressing the questions if Natamycin may foster emergence of polyene-resistance. This concern is supported by the facts that first, polyene-resistance could be elicited in vitro and in vivo . Second, as Azoles being used in agriculture and hospitals as well as polyenes share some common resistance mechanisms a polyene-resistance reservoir does exist in environmental and clinical fungal isolates. Third, Natamycin may amplify Amphothericin B resistance as fourth, resistance can in principal be spread amongst fungi by horizontal gene transfer. To preserve clinical efficacy of Amphothericin B for treatment of serious, life threatening infections, the use of Natamycin as a food-preservative should be limited to an absolute minimum.
The Role of IL-10 and TGF-β in the Differentiation and Effector Function of T Regulatory Cells

Suppression by T regulatory (Tr) cells is essential for the induction of peripheral tolerance. Many types of CD4+ Tr cells have been described in a number of systems, and although the precise mechanisms which mediate their effects remain to be defined, it is well established that they can suppress immune responses via cell-cell interactions and/or the production of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β). Type 1 T regulatory (Tr1) cells are defined by their ability to produce high levels of IL-10 and TGF-β, and these cytokines mediate their ability to suppress pathological immune responses in the settings of transplantation, allergy and autoimmune disease. Tr1 cell activity is not necessarily beneficial, and they can also suppress immune responses to antigens from tumours and pathogens. In vivo, the differentiation of Tr1 cells is likely controlled by certain dendritic cells which promote IL-10 production and may express tolerogenic costimulatory molecules. Another subset of CD4+ Tr cells is defined by constitutive expression of CD25, and although these CD4+CD25+ Tr cells appear to suppress via mechanisms which are largely independent of cytokines, they may actively promote the differentiation of Tr1 cells. Many questions about the basic biology of Tr1 cells remain to be answered, but the development of therapeutic strategies designed to harness their immunoregulatory effects can already be contemplated.
Applying the concept of "energy return on investment" to desert greening of the Sahara/Sahel using a global climate model

Abstract. Altering the large-scale dynamics of the Earth system through continual and deliberate human intervention now seems possible. In doing so, one should question the energetic sustainability of such interventions. Here, from the basis that a region might be unnaturally vegetated by employing technological means, we apply the metric of "energy return on investment" (EROI) to benchmark the energetic sustainability of such a scenario. We do this by applying EROI to a series of global climate model simulations where the entire Sahara/Sahel region is irrigated with increased rates of desalinated water to produce biomass. The energy content of this biomass is greater than the energy input rate for a minimum irrigation rate of about 200 mm yr−1 in the winter and 500 mm yr−1 in the summer, thereby yielding an EROI ratio >1 : 1, expressing energetic sustainability. Quantified annually, the EROI was >1 : 1 for irrigation rates more than 500 mm yr−1, progressively increasing to a maximum of 1.8 : 1 with 900 mm yr−1, and then decreasing with further increases in the irrigation rate. Including the precipitation feedback arising from changes in moisture recycling within the study region approximately doubles these EROI ratios. This overall result varies spatially and temporally, so while the entire Sahara/Sahel region is irrigated equally, the western coastal region from June to August had the highest EROI. Other factors would complicate such a large-scale modification of the Earth system, but this sensitivity study concludes that with a required energy input, desert greening may be energetically sustainable. More specifically, we have shown how this type of EROI analysis could be applied as a metric to assess a diverse range of human alterations to, and interventions within, the Earth system.
Trends in the Prevalence of Developmental Disabilities in US Children, 1997–2008

OBJECTIVE: To fill gaps in crucial data needed for health and educational planning, we determined the prevalence of developmental disabilities in US children and in selected populations for a recent 12-year period. PARTICIPANTS AND METHODS: We used data on children aged 3 to 17 years from the 1997–2008 National Health Interview Surveys, which are ongoing nationally representative samples of US households. Parent-reported diagnoses of the following were included: attention deficit hyperactivity disorder; intellectual disability; cerebral palsy; autism; seizures; stuttering or stammering; moderate to profound hearing loss; blindness; learning disorders; and/or other developmental delays. RESULTS: Boys had a higher prevalence overall and for a number of select disabilities compared with girls. Hispanic children had the lowest prevalence for a number of disabilities compared with non-Hispanic white and black children. Low income and public health insurance were associated with a higher prevalence of many disabilities. Prevalence of any developmental disability increased from 12.84% to 15.04% over 12 years. Autism, attention deficit hyperactivity disorder, and other developmental delays increased, whereas hearing loss showed a significant decline. These trends were found in all of the sociodemographic subgroups, except for autism in non-Hispanic black children. CONCLUSIONS: Developmental disabilities are common and were reported in ∼1 in 6 children in the United States in 2006–2008. The number of children with select developmental disabilities (autism, attention deficit hyperactivity disorder, and other developmental delays) has increased, requiring more health and education services. Additional study of the influence of risk-factor shifts, changes in acceptance, and benefits of early services is needed.
Prevalence of intestinal parasitoses in children at the Xingu Indian Reservation.

OBJECTIVE To evaluate the prevalence of intestinal parasitoses in Native Brazilian children from 2 to 9 years old. METHODS A search for ova and parasites was conducted in the stools of children between 2 to 9 years old living in six indigenous villages located in the Middle and Lower Xingu River, to wit: Pavuru, Moygu, Tuiararé, Diauarum, Capivara, and Ngojwere. The study utilized the Paratest kit® (Diagnostek, Brazil) to preserve collected stools. Fecal samples were shipped to the Laboratory of the Pediatric Gastroenterology Division of the UNIFESP/EPM, in São Paulo, for analysis. The search for ova and parasites was performed utilizing the Hoffman method, and later through optical microscopic evaluation. Fecal samples were collected one year apart from each other. RESULTS There were no significant statistical differences between the mean ages of the children from the six indigenous villages studied. The search for ova and parasites found positive results for the stools of 97.5% (198/202) and 96.1% (98/102) of children in the first and second collections, respectively. There was no statistical association with the children's age. The search performed one year later found no differences in the proportion of parasites identified in the first collection for protozoa (93.3% in 2007 versus 93.3% in 2008, McNemar = 0.01, p = 0.1) or for helminths (37.1% in 2007 versus 38.2% in 2008, McNemar = 0.03, p = 0.85). There were significant differences in prevalence of Entamoeba coli between 2007 (43.8%) and 2008 (61.8%) (McNemar Chi 6.1; p = 0.0135). There were no significant differences for other parasites when comparing the results of the two studies. CONCLUSION The high prevalence of intestinal parasitosis matched the elevated rates of environmental contamination in this indigenous community.
How Rational Could VIX Investing Be?

In the aftermath of the credit and banking crises, VIX-based ETNs have gained in popularity among under-diversified market participants since traditional diversification channels became less effective due to increasing correlations. Since then, VIX investing has attracted much heated debate about its controversial diversification benefits for passive buy-and-hold investors. We show that an uninformed utility-maximizing investor, with a feasible level of risk aversion and reasonable portfolio exposure constraints, can use VIX futures to significantly improve his optimal reference portfolio comprised of a monetary asset, equities, corporate and government bonds. We find also that VIX futures provide significant improvement over hedge funds and commodities. Our results show, however, that VIX futures investing may yield significantly lower than expected utility, which leads to disappointment for investors with higher-order moments preferences.
Lipophilicity but not stereospecificity is a major determinant of local anaesthetic-induced cytotoxicity in human T-lymphoma cells

Background and objectives Local neurotoxicity of local anaesthetics is a well known phenomenon which is determined by lipophilicity. Recent reports have indicated the relevance of local anaesthetic-induced cytotoxicity also in nonneuronal tissues. This study re-evaluates the role of lipophilicity in local anaesthetic cytotoxicity in nonneuronal cells. In addition, the toxicities of pipecoloxylidine S(−) enantiomers were investigated. Methods Local anaesthetic-induced cytotoxicity was investigated in vitro in T-lymphoma cells (Jurkat). Cells were incubated with each of eight different local anaesthetics, two esters and six amides. Annexin V-fluorescein isothiocyanate and 7-aminoactinomycin D double staining followed by flow cytometry were used to investigate the fraction of early apoptotic cells as well as the overall cell death. The concentrations leading to 50% cell death (LC50) were calculated and compared. In a second step, we compared the toxicities of S(−) bupivacaine and the racemate as well as R(+) and S(−) ropivacaine. Results Concentration-dependent cytotoxicity was observed for all investigated local anaesthetics. Apoptosis was seen at low concentrations, whereas necrosis was observed at higher concentrations. LC50 values of the different local anaesthetics yielded the following decreasing order of toxicity: tetracaine, bupivacaine, ropivacaine, prilocaine, procaine, lidocaine, articaine and mepivacaine. Toxicity correlated with octanol/buffer partition coefficients, but was independent of the ester or amide linkage. There was no effect of stereoisomerism on apoptosis and necrosis. Conclusion Moderate correlations for cytotoxicity with lipophilicity and clinical potency of local anaesthetics can be found in nonneuronal cells that are less than those reported previously with neuronal cells. Structural factors such as ester or amide linkage or stereospecificity do not have any influence on cytotoxicity. Although S(−) enantiomers may be advantageous with regard to systemic toxicity, they have no advantage in respect of local cytotoxicity in vitro.
[Gender-related difference in patients with aortic dissection from Guangzhou].

OBJECTIVE To investigate gender-related differences in risk factors, clinical manifestation and outcomes in patients with aortic dissection (AD) from Guangzhou. METHODS Consecutive patients with AD admitted to our institute over the past 10 years were included in this retrospective analysis. Prevalence of hypertension, smoking, thickness of intraventricular septum and left ventricular posterior wall measured by echocardiography, and outcomes were compared between male and female AD patients. RESULTS There were more male AD patients than female AD patients (5.33:1) from the 418 patients. Prevalence of hypertension, thickness of intraventricular septum and left ventricular posterior wall were similar in male and female AD patients. Heavy smoking history was 56.5% in males and 13.6% in females (P = 0.000). Acute survival rate in female patients tended to be better than that in male patients. CONCLUSIONS There were significantly more male AD patients than female AD patients in this cohort. Prevalence of heave smoking in male patients is 3 times higher than that in female population.
Sestrin 2 Protein Regulates Platelet-derived Growth Factor Receptor β (Pdgfrβ) Expression by Modulating Proteasomal and Nrf2 Transcription Factor Functions*

Background: Sestrin 2 is a redox-dependent repressor of Pdgfrβ signaling and thereby interferes with lung injury repair. Results: Sestrin 2 is a positive regulator of proteasomal function and activates transcription of Nrf2-regulated antioxidant genes. Conclusion: Sestrin 2 is a component of a novel Sestrin 2/Pdgfrβ repressor pathway. Significance: The Sestrin2/Pdgfrβ repressor pathway is likely to play role in the pathogenesis of chronic obstructive pulmonary disease (COPD). We recently identified the antioxidant protein Sestrin 2 (Sesn2) as a suppressor of platelet-derived growth factor receptor β (Pdgfrβ) signaling and Pdgfrβ signaling as an inducer of lung regeneration and injury repair. Here, we identified Sesn2 and the antioxidant gene inducer nuclear factor erythroid 2-related factor 2 (Nrf2) as positive regulators of proteasomal function. Inactivation of Sesn2 or Nrf2 induced reactive oxygen species-mediated proteasomal inhibition and Pdgfrβ accumulation. Using bacterial artificial chromosome (BAC) transgenic HeLa and mouse embryonic stem cells stably expressing enhanced green fluorescent protein-tagged Sesn2 at nearly endogenous levels, we also showed that Sesn2 physically interacts with 2-Cys peroxiredoxins and Nrf2 albeit under different reductive conditions. Overall, we characterized a novel, redox-sensitive Sesn2/Pdgfrβ suppressor pathway that negatively interferes with lung regeneration and is up-regulated in the emphysematous lungs of patients with chronic obstructive pulmonary disease (COPD).
E3-ubiquitin ligase Nedd4 determines the fate of AID-associated RNA polymerase II in B cells

During B-lymphocyte class switch recombination, mutagenesis of the immunoglobulin (Ig) locus requires RNA polII-dependent targeting of the DNA mutator AID, yet the mechanism is unknown. Sun et al. now show that E3-ubiquitin ligase Nedd4 destabilizes AID-associated RNA polII at Ig switch regions. Loss of Nedd4 activity leads to RNA exosome substrate accumulation at AID target genes. This study links noncoding RNA processing following RNA polII pausing with AID regulation during class switch recombination.
Long-Term Changes of Plasma Trace Element Concentrations in Chronic Hemodialysis Patients

Background: Hemodialysis (HD) patients are at risk of developing trace element imbalances. Methods: The 12 trace elements Cd, Co, Cs, Cu, La, Mg, Mo, Pb, Rb, Sr, Tl and Zn were determined in the plasma (n = 52) of 6 chronic HD patients before and after HD sessions by inductively coupled plasma mass spectrometry. Plasma trace element concentrations were monitored for 6 months. Baseline data have been compared to the concentrations at the end of the observation period to identify a potential reduction or accumulation of trace elements in HD patients. Results: Plasma Cd, Co and Pb levels were about 10 times higher than in healthy adults. Concentrations of Co and Pb increased during HD sessions, whereas plasma Co and Cd increased during the study period of 6 months. Plasma Cs, Mg, Mo and Rb continuously decreased in all patients. For plasma Cu and Zn, a statistically significant rise of their plasma concentrations during HD and during the period of 6 months could be established. Concentrations of La and Tl did not change distinctly. Conclusion: This study revealed that plasma trace element concentrations in HD patients are distinctly different compared to that of healthy adults. Elements such as Cs, Mg, Mo and Rb are reduced and Cd, Co and Pb are accumulated in HD patients. Further studies are needed to elucidate the clinical impact of these trace element imbalances.
Physical activity and sedentary activity patterns among children and adolescents: a latent class analysis approach.

BACKGROUND While much is known about the overall levels of physical activity and sedentary activity among youth, few studies have attempted to define clusters of such behaviors. The purpose of this study was to identify and describe unique classes of youth based on their participation in a variety of physical activity and sedentary behaviors. METHODS Latent class analysis was used to characterize segments of youth based on patterns of self-reported and accelerometer-measured participation in 12 behaviors. Children and adolescents (N=720) from 6th-11th grade were included in the analysis. Differences in class membership were examined using multinomial logistic regression. RESULTS Three distinct classes emerged for boys and girls. Among boys, the 3 classes were characterized as "Active" (42.1%), "Sedentary" (24.9%), and "Low Media/Moderate Activity" (33.0%). For girls, classes were "Active" (18.7%), "Sedentary" (47.6%), and "Low Media/Functional Activity" (33.7%). Significant differences were found between the classes for a number of demographic indicators including the proportion in each class who were classified as overweight or obese. CONCLUSIONS The behavioral profiles of the classes identified in this study can be used to suggest possible audience segments for intervention and to tailor strategies appropriately.
Measuring e-Government Maturity: A meta-synthesis approach

Abstract Many governments in the world have created e-government initiatives including developed and developing countries. In order to better understand e-government evolution, different maturity models have been developed by many authors. In this paper the most cited e-government maturity models are analyzed using the meta-synthesis approach. As a result, five stages of e-government maturity are identified. The comparative results show the supported stages by each e-government initiative as important elements in the decision making process. This paper is attempting to show that although there are many models for measuring e-government maturity, they all converge on one common model. The contribution of this paper is in simplifying work for researchers when choosing the right maturity model.
Vocal characteristics in pre-adolescent and adolescent children: a longitudinal study

A number of cross-sectional studies have been reported for the fundamental frequency and formant frequency data in the voices of a group of 20 pre-adolescent children aged between 6 and 10 years (Whiteside, SP, Hodgson, C. Acoustic characteristics in 6-10-year old children's voices: some preliminary findings, Log Phon Vocol 1999; 24: 6-13, Whiteside, SP, Hodgson, C. Some acoustic characteristics in the voices of 6-10-year-old children and adults: a comparative sex and developmental perspective, Log Phon Vocol 2000; 25: 122-132). About 15 of the children who participated in these earlier studies, participated in a follow-up study approximately 42 months later. Their speech data were recorded and analysed acoustically to investigate longitudinal patterns of development in their voices by examining data for fundamental frequency and the first three formant frequencies of a phrase final vowel. Data obtained from this follow-up study (Time 2) were compared with earlier corresponding data (Time 1). The findings of this study indicated that there was evidence for maturation in the voice parameters of all subjects between Time 1 and 2, with changes being observed for the majority of comparisons for parameters, across age and sex. In addition there was also evidence of individual differences in the maturational patterns which were observed. These individual differences highlight the degree of variation which occurs in the developmental changes of voice characteristics.
A mutation at proline-115 in the A-factor receptor protein of Streptomyces griseus abolishes DNA-binding ability but not ligand-binding ability

A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) and its specific receptor protein (ArpA) are required for streptomycin production and aerial mycelium formation in Streptomyces griseus. A mutant strain HO1 that produced streptomycin and formed aerial mycelium and spores was derived from an A-factor-deficient mutant, S. griseus HH1. The phenotypes of mutant HO1 were found to result from a single amino acid replacement of ArpA; the proline residue at position 115 in the wild-type ArpA was replaced by serine, yielding mutant ArpA (P115S). The mutant ArpA (P115S) was still able to form a homodimer and possessed A-factor-binding ability but lost the ability to bind DNA. The properties of P115S suggest that ArpA consists of two independently functional domains, one for A-factor binding and one for DNA binding, and that proline-115 plays an important role in DNA binding. This is in agreement with the idea that A-factor binding to the COOH-terminal domain of ArpA causes a subtle conformational change of the distal NH2-terminal DNA-binding domain, resulting in dissociation of ArpA from DNA.
Effect of anterior cruciate healing on the uninjured ligament insertion site

The effect of anterior cruciate healing on the uninjured ligament insertion site after enhanced suture repair with collagen‐platelet composites (CPC) has not yet been defined. In this study, we hypothesized that fibroblasts and osteoclasts would participate in generating histologic changes in insertion site morphology after transection and bioenhanced repair of the ACL, and that these changes would be age‐dependent. Skeletally immature, adolescent, and adult Yucatan mini‐pigs underwent ACL transection and bioenhanced suture repair. The histologic response to repair of the insertion site was evaluated at 1, 2, 4, and 15 weeks. In young and adolescent animals treated with bioenhanced suture repair with CPC, changes in the insertion site included: (1) fibroblastic proliferation with loss and return of collagen alignment in the fibrous zone; (2) osteoclastic resorption within fibrocartilage zones at 2–4 weeks; and (3) partial reappearance of fibrocartilage zones at 15 weeks. In adult animals; however, degenerative changes were noted by 15 weeks: (1) loss of parallel arrangement of collagen fibers in the fibrous zone; and (2) increasing disorganization and loss of columnation of chondrocytes in the fibrocartilage zone. These results suggest that fibroblasts and osteoclasts mediate histologic changes at the insertion site during bioenhanced suture repair of the ACL which may prevent insertion site degeneration, and that the magnitude of these changes may be a function of skeletal maturity. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:86–94, 2012