Pathological profiles of systemic infections by Panton-Valentine leukocidin-positive, methicillin-resistant Staphylococcus aureus strains in a murine model.

AIMS: Staphylococcus aureus is one of the most common pathogens in hospital environment and community. Panton-Valentine leukocidin (PVL) production is clinically associated with skin abscesses, soft tissues infections, bacteraemia and sepsis. This study aimed to investigate the effects of the presence of genes lukF/S-PV coding for PVL, in histological and haematological features during systemic infection, using a Swiss mice experimental model. METHODS AND RESULTS: Experiments were performed using 25 mice distributed into five experimental groups, intravenously inoculated with 50 µl suspensions at density 1·0 × 107  CFU per ml of strains: methicillin-susceptible (MSSA) and pvl-negative strains isolated from nasal colonization; MSSA pvl-positive strains isolated from nasal colonization; methicillin-resistant (MRSA) and pvl-positive strains isolated from peripheral blood of a patient with severe pulmonary infection; and a MRSA pvl-positive strains isolated from a peripheral blood culture of a patient with bacteraemia. Haematological analysis was performed at 24, 48, 72 and 96 h post-infection. Morphoanatomy and histopathological analyses were performed at 96 h post-infection. For all S. aureus strains tested, the capability of intravenous dissemination and survival into mice tissues was demonstrated. Inflammatory processes at different levels were related to the presence of pvl genes, and included alterations in the format, size and colour of the organs. Staphylococcus aureus pvl-positive strains were detected in greater numbers in the organs of the infected animals. CONCLUSIONS: The pvl-positive strains isolated from blood cultures were capable to induce the greatest modifications in both haematological and histopathological profiles, and seemed to aggravate the systemic infections. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings are valuable in characterizing infections caused by S. aureus in humans and murine.

A Promising Antiprion Trimethoxychalcone Binds to the Globular Domain of the Cellular Prion Protein and Changes Its Cellular Location.

The search for antiprion compounds has been encouraged by the fact that transmissible spongiform encephalopathies (TSEs) share molecular mechanisms with more prevalent neurodegenerative pathologies, such as Parkinson's and Alzheimer's diseases. Cellular prion protein (PrPC) conversion into protease-resistant forms (protease-resistant PrP [PrPRes] or the scrapie form of PrP [PrPSc]) is a critical step in the development of TSEs and is thus one of the main targets in the screening for antiprion compounds. In this work, three trimethoxychalcones (compounds J1, J8, and J20) and one oxadiazole (compound Y17), previously identified in vitro to be potential antiprion compounds, were evaluated through different approaches in order to gain inferences about their mechanisms of action. None of them changed PrPC mRNA levels in N2a cells, as shown by reverse transcription-quantitative real-time PCR. Among them, J8 and Y17 were effective in real-time quaking-induced conversion reactions using rodent recombinant PrP (rPrP) from residues 23 to 231 (rPrP23-231) as the substrate and PrPSc seeds from hamster and human brain. However, when rPrP from residues 90 to 231 (rPrP90-231), which lacks the N-terminal domain, was used as the substrate, only J8 remained effective, indicating that this region is important for Y17 activity, while J8 seems to interact with the PrPC globular domain. J8 also reduced the fibrillation of mouse rPrP23-231 seeded with in vitro-produced fibrils. Furthermore, most of the compounds decreased the amount of PrPC on the N2a cell surface by trapping this protein in the endoplasmic reticulum. On the basis of these results, we hypothesize that J8, a nontoxic compound previously shown to be a promising antiprion agent, may act by different mechanisms, since its efficacy is attributable not only to PrP conversion inhibition but also to a reduction of the PrPC content on the cell surface.

Pediatric laryngeal carcinoma in a heterozygous carrier of Fanconi anemia.

A case of invasive, keratinizing squamous cell carcinoma of the larynx in an 8-year-old female treated with laryngectomy is presented. Perinatal exposure to human papilloma virus and constitutional heterozygosity for a FANCC mutation were identified, though FANCC heterozygosity is not known to be cancer predisposing. An additional tumor-associated mutation in NOTCH1 was also identified potentially contributing to oncogenesis. This case illustrates an exceedingly rare type of cancer in the pediatric population and discusses diagnostic workup, evaluation of risk factors for head and neck cancer, and treatment options.

Exercise and the multidisciplinary holistic approach to adolescent dysautonomia.

AIM: To determine whether an eight-week strength training programme as part of a multidisciplinary approach would minimise symptoms and improve quality of life in patients with dysautonomia. METHODS: Adolescents referred to a tertiary-level cardiology service from May 2014-December 2015 with symptoms of dysautonomia were eligible. Participants completed an exercise test and a quality of life (QoL) questionnaire (PedsQL) prior to the intervention. Participants were asked to complete exercises five times per week. After eight weeks, participants returned for follow-up testing. Parents completed a proxy report of their child's QoL at both time points. RESULTS: A total of 17 participants completed the study protocol with an adherence rate of up to 50%. Post-intervention, QoL scores improved across all levels in the participants [total 65.2 (50.4-74.7) vs 48.9 (37.5-63.0); p = 0.006; psychosocial 65.8 (56.1-74.6) vs 50.0 (41.7-65.8); p = 0.010; physical 62.5 (37.5-76.6) vs 43.8 (25-68.5); p = 0.007] and their parent proxy reports [total 63.5 (48.7-81.3) vs 50.0 (39.3-63.0); p = 0.004; psychosocial 62.1 (52.1-81.3) vs 50.0 (39.6-59.2); p = 0.001; physical 62.5 (51.6-80.0) vs 50.0 (27.5-70.3); p = 0.003]. Treadmill time also improved (9.1 vs 8.0 minutes; p = 0.005). CONCLUSION: Following an eight-week strength training programme, dysautonomia patients report a significant improvement in both their quality of life and endurance time.

Irreversibility and the Arrow of Time in a Quenched Quantum System.

Irreversibility is one of the most intriguing concepts in physics. While microscopic physical laws are perfectly reversible, macroscopic average behavior has a preferred direction of time. According to the second law of thermodynamics, this arrow of time is associated with a positive mean entropy production. Using a nuclear magnetic resonance setup, we measure the nonequilibrium entropy produced in an isolated spin-1/2 system following fast quenches of an external magnetic field. We experimentally demonstrate that it is equal to the entropic distance, expressed by the Kullback-Leibler divergence, between a microscopic process and its time reversal. Our result addresses the concept of irreversibility from a microscopic quantum standpoint.

Comparison of methods for estimates of molecular genetic diversity in genus Croton: influence of coefficients, clustering strategies and data projection.

We investigated 10 similarity (and disimilarity) coefficients in a set of 40 wild genotypes of Croton linearifolius subjected to analyses using hierarchical grouping methods, grouping methods by optimization and data projection in two-dimensional space. Genotypes were characterized by analyzing DNA polymorphism with the use of 15 ISSR and 12 RAPD markers. The distance measurements were compared by the Spearman correlation test, projection in two-dimensional space and grouping efficiency evaluation. The Spearman correlation coefficients between the 10 coefficients evaluated were significant (P < 0.001) and indicated significant changes in genotype ranking due to type of coefficient used (0.76 ≤ rs ≤ 1). Wide variation was also observed in the efficiency of clustering methods, where the unweighted pair group method with arithmetic mean was the most suitable (0.3 ≤ D ≤ 1.5 ; 0.41 ≤ rc ≤ 0.77; 5.99 ≤ S ≤ 12.61). Projection efficiencies in two-dimensional space showed high-stress values (65 < S < 89%). Similar to the results observed for hierarchical clustering methods and for projection in two-dimensional space, the formation of groups with grouping methods by optimization showed variations when using different coefficients. We believe that the results confirm the influence of coefficients in studies of genetic diversity, showing the need to use criteria and standards for selecting appropriate methods for genetic studies of the genus Croton.

Observation of environment-induced double sudden transitions in geometric quantum correlations.

Correlations in quantum systems exhibit a rich phenomenology under the effect of various sources of noise. We investigate theoretically and experimentally the dynamics of quantum correlations and their classical counterparts in two nuclear magnetic resonance setups, as measured by geometric quantifiers based on trace norm. We consider two-qubit systems prepared in Bell diagonal states, and perform the experiments in real decohering environments resulting from Markovian local noise which preserves the Bell diagonal form of the states. We then report the first observation of environment-induced double sudden transitions in the geometric quantum correlations, a genuinely nonclassical effect not observable in classical correlations. The evolution of classical correlations in our physical implementation reveals in turn the finite-time relaxation to a pointer basis under nondissipative decoherence, which we characterize geometrically in full analogy with predictions based on entropic measures.

Comparison of efficiency of distance measurement methodologies in mango (Mangifera indica) progenies based on physicochemical descriptors.

We investigated seven distance measures in a set of observations of physicochemical variables of mango (Mangifera indica) submitted to multivariate analyses (distance, projection and grouping). To estimate the distance measurements, five mango progeny (total of 25 genotypes) were analyzed, using six fruit physicochemical descriptors (fruit weight, equatorial diameter, longitudinal diameter, total soluble solids in °Brix, total titratable acidity, and pH). The distance measurements were compared by the Spearman correlation test, projection in two-dimensional space and grouping efficiency. The Spearman correlation coefficients between the seven distance measurements were, except for the Mahalanobis' generalized distance (0.41 ≤ rs ≤ 0.63), high and significant (rs ≥ 0.91; P < 0.001). Regardless of the origin of the distance matrix, the unweighted pair group method with arithmetic mean grouping method proved to be the most adequate. The various distance measurements and grouping methods gave different values for distortion (-116.5 ≤ D ≤ 74.5), cophenetic correlation (0.26 ≤ rc ≤ 0.76) and stress (-1.9 ≤ S ≤ 58.9). Choice of distance measurement and analysis methods influence the.

Structure-activity relationship, molecular docking, and molecular dynamic studies of diterpenes from marine natural products with anti-HIV activity.

HIV-1 infection is a global epidemic whose treatment is limited majorly by viral resistance and adverse effects. Natural products from algae have been studied for many years, including antiviral, being an alternative to anti-HIV drug design. Since the isolation of natural products can be a hurdle, molecular modeling is an important tool to study these compounds. Herein, structure-activity relationship, molecular docking, and molecular dynamic studies were performed to direct the studies of ten marine natural products with anti-HIV activity. In the structure-activity relationship, descriptors were identified associating the anti-HIV activity of five diterpenes with possible action on the reverse transcriptase allosteric site. These diterpenes were evaluated by molecular docking, and it was identified that only dolabelladienetriol interacted in the allosteric site. Molecular dynamics suggested that the dolabelladienetriol might interfere with the viral RNA binding to HIV-1 RT by inducing a conformational change of the enzyme. Also, in silico ADMET simulations predicts that the dolabelladienetriol present a high potential to be successfully developed as a drug. Thus, applying in silico approaches was possible to suggest potential anti-HIV compounds derived from marine natural products.Communicated by Ramaswamy H. Sarma.

Environment-induced sudden transition in quantum discord dynamics.

Nonclassical correlations play a crucial role in the development of quantum information science. The recent discovery that nonclassical correlations can be present even in separable (nonentangled) states has broadened this scenario. This generalized quantum correlation has been increasing in relevance in several fields, among them quantum communication, quantum computation, quantum phase transitions, and biological systems. We demonstrate here the occurrence of the sudden-change phenomenon and immunity against some sources of noise for the quantum discord and its classical counterpart, in a room temperature nuclear magnetic resonance setup. The experiment is performed in a decohering environment causing loss of phase relations among the energy eigenstates and exchange of energy between system and environment, resulting in relaxation to the Gibbs ensemble.

The effect of hormones on endometriosis development.

Endometriosis is a common gynecological condition in which tissue that is histologically similar to the endometrium with glands and/or stroma grows outside the uterine cavity and can lead to pelvic pain, dysmenorrhea and infertility. Many aspects of female reproductive function are strongly influenced by genetic factors and numerous studies have attempted to identify susceptibility genes for disorders affecting female fertility such as endometriosis. The importance of steroid hormones on endometriosis is unquestionable. The disease is most prevalent in women of reproductive age and regresses after menopause and its occurrence before menarche has not been reported. Sex steroids, estrogen and progesterone, are mainly produced in the ovaries and they regulate the growth of endometrial tissue, basically by stimulating and inhibiting cell proliferation, respectively. In addition, estrogen plays an important role in the regulation of cyclic gonadotropin release and in folliculogenesis. Numerous studies have been conducted to demonstrate the interaction of hormone and their receptors with endometriosis with conflict results. Besides, environmental chemicals, known as endocrine disruptors, have the capacity to mimic, block or modulate the endocrine system through the interaction with steroidal receptors. Recently evidences have proposed a putative role for ubiquitous environmental contaminants in the occurrence of endometriosis. Here, we reviewed significant articles regarding the interaction among endometriosis, hormones and genetic polymorphic variants.

Ecotoxicological effects of commercial herbicides on the reproductive system of aquatic arthropod Limnocoris submontandoni (Hemiptera: Naucoridae).

Worldwide, conventional agriculture makes extensive use of pesticides. Although the effects of herbicides are relatively well known in terms of environmental impacts on non-target organisms, there is very little scientific evidence regarding the impacts of herbicide residues on aquatic arthropods from tropical conservation areas. This study evaluates for the first time the toxicity of the herbicides ametryn, atrazine, and clomazone on the aquatic insect Limnocoris submontandoni (Hemiptera: Naucoridae). The lethal concentration (LC50) of herbicides was evaluated for these insects, as well as the effect of the herbicides on the insects' tissues and testicles. The estimated LC50 was 1012.41, 192.42, and 46.09 mg/L for clomazone, atrazine, and ametryn, respectively. Spermatocyte and spermatid changes were observed under the effect of atrazine, and effects on spermatogenesis were observed for some concentrations of clomazone, with apparent recovery after a short time. Our results provide useful information on the effects of herbicide residues in aquatic systems. This information can help minimize the risk of long-term reproductive effects in non-target species that have been previously overlooked in ecotoxicology studies.

Molecular cloning and expression of epsilon toxin from Clostridium perfringens type D and tests of animal immunization.

Epsilon toxin produced by Clostridium perfringens types B and D causes enterotoxemia in sheep, goats and calves. Enterotoxemia can cause acute or superacute disease, with sudden death of the affected animal. It provokes huge economic losses when large numbers of livestock are affected. Therapeutic intervention is challenging, because the disease progresses very rapidly. However, it can be prevented by immunization with specific immunogenic vaccines. We cloned the etx gene, encoding epsilon toxin, into vector pET-11a; recombinant epsilon toxin (rec-epsilon) was expressed in inclusion bodies and was used for animal immunization. Serum protection was evaluated and cross-serum neutralization tests were used to characterize the recombinant toxin. To analyze the potency of the toxin (as an antigen), rabbits were immunized with 50, 100 or 200 microg recombinant toxin, using aluminum hydroxide gel as an adjuvant. Titers of 10, 30 and 40 IU/mL were obtained, respectively. These titers were higher than the minimum level required by the European Pharmacopoeia (5 IU/mL) and by the USA Code of Federal Regulation (2 IU/mL). This rec-epsilon is a good candidate for vaccine production against enterotoxemia caused by epsilon toxin of C. perfringens type D.

Traffic-flow cellular automaton: order parameter and its conjugated field.

We use a cellular automaton traffic model in order to study a nonequilibrium phase transition. We define an order parameter and show that its conjugated field is a parameter of randomness of the model. We analyze the symmetries of the free (unbroken) and of the jammed (broken) phases. Our results are consistent with a second-order phase transition at p=0 . Nontrivial critical exponents have also been obtained.

Enhanced NMR relaxation of fluids confined to porous media: A proposed theory and experimental tests.

We propose a theory to account for the NMR relaxation of water protons in situations in which the fluid is confined to porous structures exhibiting a scarce distribution of paramagnetic centers on their surface. Though much of what is stated and assumed concerns the response of water, the model has sufficiently general features to be able to explain proton relaxation of other polar fluids under similar conditions. One of the main results of the paper is to show that the local anisotropy introduced by the dominant dipolar coupling in the relaxation rates of active surface elements induces a measurable dependence on sample orientation in the overall relaxation rates of the saturating fluid provided its confining structure is not statistically isotropic. Measurements of T_{1} proton relaxation on water saturating microcapillary tubes are performed to reveal the effect.

Coffea arabica and C. canephora discrimination in roasted and ground coffee from reference material candidates by real-time PCR.

To produce specific desirable coffee blends, Coffea arabica and C. canephora are mixed each other, in some cases to suit consumer preference, but in others to reduce production costs. In this scenario, the aim of this work was to evaluate standard candidate reference materials (RMc) for analysis of different blends of roasted and ground coffee. For this purpose, we analyzed different percentages of C. arabica and C. canephora (100:0; 50:50; 25:75; and 0:100, respectively). These RMc samples were developed in a previous study with green coffee beans submitted to medium roasting. In this work, coffee species differentiation (C. arabica and C. canephora) was analyzed by real-time PCR, using specific primers previously developed, called ARA primers. The RMc material with 100% C. canephora did not present amplification, in contrast with the samples containing C. arabica, which all presented amplification. These results indicate the specificity of ARA primers for C. arabica and that the detection system assay can be used as a promising molecular tool to identify and quantify percentages of C. arabica in different coffee blends.

Ecotoxicological effects of commercial herbicides on the reproductive system of aquatic arthropod Limnocoris submontandoni (Hemiptera: Naucoridae)

Abstract Worldwide, conventional agriculture makes extensive use of pesticides. Although the effects of herbicides are relatively well known in terms of environmental impacts on non-target organisms, there is very little scientific evidence regarding the impacts of herbicide residues on aquatic arthropods from tropical conservation areas. This study evaluates for the first time the toxicity of the herbicides ametryn, atrazine, and clomazone on the aquatic insect Limnocoris submontandoni (Hemiptera: Naucoridae). The lethal concentration (LC50) of herbicides was evaluated for these insects, as well as the effect of the herbicides on the insects tissues and testicles. The estimated LC50 was 1012.41, 192.42, and 46.09 mg/L for clomazone, atrazine, and ametryn, respectively. Spermatocyte and spermatid changes were observed under the effect of atrazine, and effects on spermatogenesis were observed for some concentrations of clomazone, with apparent recovery after a short time. Our results provide useful information on the effects of herbicide residues in aquatic systems. This information can help minimize the risk of long-term reproductive effects in non-target species that have been previously overlooked in ecotoxicology studies.

Resumo Em todo o mundo, a agricultura convencional faz uso extensivo de pesticidas. Embora os efeitos dos herbicidas sejam relativamente bem conhecidos em termos de impactos ambientais em organismos não-alvo, há pouca evidência científica sobre os impactos de resíduos de herbicidas em artrópodes aquáticos de áreas de conservação tropicais. Este estudo avalia pela primeira vez a toxicidade dos herbicidas ametryn, atrazine e clomazone sobre o inseto aquático Limnocoris submontandoni (Hemiptera: Naucoridae). A concentração letal (LC50) de herbicidas foi avaliada para esses insetos, bem como o efeito dos herbicidas nos tecidos e testículos dos insetos. A LC50 estimada foi de 1012,41, 192,42 e 46,09 mg/L para clomazone, atrazine e ametryn, respectivamente. Alterações nos espermatócitos e espermátides foram observadas sob o efeito de atrazine, e efeitos na espermatogênese foram observados para algumas concentrações de clomazone, com aparente recuperação após um curto período de tempo. Nossos resultados fornecem informações úteis sobre os efeitos de resíduos de herbicidas em sistemas aquáticos. Essas informações podem ajudar a minimizar o risco de efeitos reprodutivos de longo prazo em espécies não-alvo que foram negligenciadas anteriormente em estudos de ecotoxicologia.

Ecotoxicological effects of commercial herbicides on the reproductive system of aquatic arthropod Limnocoris submontandoni (Hemiptera: Naucoridae) / Efeitos ecotoxicológicos de herbicidas comerciais no sistema reprodutivo do artrópode aquático Limnocoris submontandoni (Hemiptera: Naucoridae)

Abstract Worldwide, conventional agriculture makes extensive use of pesticides. Although the effects of herbicides are relatively well known in terms of environmental impacts on non-target organisms, there is very little scientific evidence regarding the impacts of herbicide residues on aquatic arthropods from tropical conservation areas. This study evaluates for the first time the toxicity of the herbicides ametryn, atrazine, and clomazone on the aquatic insect Limnocoris submontandoni (Hemiptera: Naucoridae). The lethal concentration (LC50) of herbicides was evaluated for these insects, as well as the effect of the herbicides on the insects' tissues and testicles. The estimated LC50 was 1012.41, 192.42, and 46.09 mg/L for clomazone, atrazine, and ametryn, respectively. Spermatocyte and spermatid changes were observed under the effect of atrazine, and effects on spermatogenesis were observed for some concentrations of clomazone, with apparent recovery after a short time. Our results provide useful information on the effects of herbicide residues in aquatic systems. This information can help minimize the risk of long-term reproductive effects in non-target species that have been previously overlooked in ecotoxicology studies.

Resumo Em todo o mundo, a agricultura convencional faz uso extensivo de pesticidas. Embora os efeitos dos herbicidas sejam relativamente bem conhecidos em termos de impactos ambientais em organismos não-alvo, há pouca evidência científica sobre os impactos de resíduos de herbicidas em artrópodes aquáticos de áreas de conservação tropicais. Este estudo avalia pela primeira vez a toxicidade dos herbicidas ametryn, atrazine e clomazone sobre o inseto aquático Limnocoris submontandoni (Hemiptera: Naucoridae). A concentração letal (LC50) de herbicidas foi avaliada para esses insetos, bem como o efeito dos herbicidas nos tecidos e testículos dos insetos. A LC50 estimada foi de 1012,41, 192,42 e 46,09 mg/L para clomazone, atrazine e ametryn, respectivamente. Alterações nos espermatócitos e espermátides foram observadas sob o efeito de atrazine, e efeitos na espermatogênese foram observados para algumas concentrações de clomazone, com aparente recuperação após um curto período de tempo. Nossos resultados fornecem informações úteis sobre os efeitos de resíduos de herbicidas em sistemas aquáticos. Essas informações podem ajudar a minimizar o risco de efeitos reprodutivos de longo prazo em espécies não-alvo que foram negligenciadas anteriormente em estudos de ecotoxicologia.