Zoonotic cutaneous leishmaniasis due to Leishmania (Viannia) braziliensis associated with domestic animals in Venezuela and Brazil

After outbreaks of cutaneous leishmaniasis in Solano State, Venezuela, 5% of the population had parasitized ulcers while after similar outbreaks in Mesquita, Rio de Janeiro State, Brazil, 9% had the disease. In these foci children, including some under six years of age, were affected. There was no significant difference in the occurrence of the disease according to sex or type of employment. In Solano, 3% of dogs and 28% of donkeys had parasitized lesions, while in Mesquita these indices were 19.8% and 30.8% respectively. The parasite from man, dogs and equines was identified as Leishmania (Viannia) braziliensis, by zymodeme and serodeme characterization. In these foci there is evidence suggesting that leishmaniasis is a zoonosis, possibly with equines and dogs as reservoirs, although both a wild enzootic cycle and the role of man as a source of infection can not be ruled out. Transmission is assumed to occur peridomestically by sandfly vectors such as Lutzomyia panamensis in Venezuela and Lutzomyia intermedia in Brazil. Information about the origin of these foci suggests that infected equines may be an important factor in the dissemination of the parasite in a peridomestic situation where these sandflies are abundant.     

Proposed guidelines to evaluate scientific validity and evidence for genotype-based dietary advice

Nutrigenetic research examines the effects of inter-individual differences in genotype on responses to nutrients and other food components, in the context of health and of nutrient requirements. A practical application of nutrigenetics is the use of personal genetic information to guide recommendations for dietary choices that are more efficacious at the individual or genetic subgroup level relative to generic dietary advice. Nutrigenetics is unregulated, with no defined standards, beyond some commercially adopted codes of practice. Only a few official nutrition-related professional bodies have embraced the subject, and, consequently, there is a lack of educational resources or guidance for implementation of the outcomes of nutrigenetic research. To avoid misuse and to protect the public, personalised nutrigenetic advice and information should be based on clear evidence of validity grounded in a careful and defensible interpretation of outcomes from nutrigenetic research studies. Evidence requirements are clearly stated and assessed within the context of state-of-the-art ‘evidence-based nutrition’. We have developed and present here a draft framework that can be used to assess the strength of the evidence for scientific validity of nutrigenetic knowledge and whether ‘actionable’. In addition, we propose that this framework be used as the basis for developing transparent and scientifically sound advice to the public based on nutrigenetic tests. We feel that although this area is still in its infancy, minimal guidelines are required. Though these guidelines are based on semi-quantitative data, they should stimulate debate on their utility. This framework will be revised biennially, as knowledge on the subject increases.     

Tuned inhibition in perceptual decision-making circuits can explain seemingly suboptimal confidence behavior

Current dominant views hold that perceptual confidence reflects the probability that a decision is correct. Although these views have enjoyed some empirical support, recent behavioral results indicate that confidence and the probability of being correct can be dissociated. An alternative hypothesis suggests that confidence instead reflects the magnitude of evidence in favor of a decision while being relatively insensitive to the evidence opposing the decision. We considered how this alternative hypothesis might be biologically instantiated by developing a simple neural network model incorporating a known property of sensory neurons: tuned inhibition. The key idea of the model is that the level of inhibition that each accumulator unit receives from units with the opposite tuning preference, i.e. its inhibition ‘tuning’, dictates its contribution to perceptual decisions versus confidence judgments, such that units with higher tuned inhibition (computing relative evidence for different perceptual interpretations) determine perceptual discrimination decisions, and units with lower tuned inhibition (computing absolute evidence) determine confidence. We demonstrate that this biologically plausible model can account for several counterintuitive findings reported in the literature where confidence and decision accuracy dissociate. By comparing model fits, we further demonstrate that a full complement of behavioral data across several previously published experimental results—including accuracy, reaction time, mean confidence, and metacognitive sensitivity—is best accounted for when confidence is computed from units without, rather than units with, tuned inhibition. Finally, we discuss predictions of our results and model for future neurobiological studies. These findings suggest that the brain has developed and implements this alternative, heuristic theory of perceptual confidence computation by relying on the diversity of neural resources available.     

Leishmania mexicana amazonensis: heterogeneity in 5'-nucleotidase and peroxidase activities of mononuclear phagocytes during in vivo and in vitro infection

The degree of maturation of cells of the Mononuclear Phagocyte System (MPS), during in vivo and in vitro infection by Leishmania mexicana amazonensis, was evaluated in this study. The macrophages' differentiation was assayed by cytochemical characterization at the ultrastructural level, using two well-established markers: 5'-nucleotidase enzyme activity, for revealing the mature cells; and the peroxidase activity present in the cell granules to demonstrate immature mononuclear phagocytes. Only a few macrophages, demonstrating 5'-nucleotidase positive reaction in both the plasma membrane and within their cytoplasmic vesicles, were found scattered in the chronic inflammation at the L. m. amazonensis lesions in albino mice. However, by the peroxidase activity analysis, we were also able to demonstrate the presence of immature MPS cells, which predominate, together with parasitized vacuolated macrophages, in chronic lesions induced in this system by L. m. amazonensis. The implications of these results on the pathogenesis of murine cutaneous leishmaniasis are discussed.     

Redox thermodynamics of mutant forms of the rubredoxin from Clostridium pasteurianum: identification of a stable FeIII(S-Cys)3(OH) centre in the C6S mutant

Redox thermodynamic data provide a detailed insight into control of the reduction potential E degrees' of the [Fe(S-Cys)4] site in rubredoxin. Mutant forms were studied in which specific structural changes were made in both the primary and secondary coordination spheres. Those changes have been probed by resonance Raman spectroscopy. The decrease of approximately 200 mV in E degrees' observed for the [Fe(S-Cys)3(O-Ser)]-/2- couples in the surface ligand mutants C9S and C42S is essentially enthalpic in origin and associated with the substitution of ligand thiolate by ligand olate. However, the pH dependence of the potentials below characteristic pKa(red) approximately equals 7 is an entropic contribution, plausibly associated with increased conformational flexibility induced by a longer Fe(II)-O(H)-Ser bond in the reduced form. The presence of a second surface Ser ligand in the new double mutant protein C9S/C42S affects the enthalpic term primarily for pH>pKa(red) > or = 9.3, but for pHpKa approximately 9: [Fe(III)(S-Cys)3(OH)]- + e- --> [Fe(II)(S-Cys)3(OH)]2-. pH [Fe(II)(S-Cys)3(OH2)]-.     

Immunopathology of American cutaneous leishmaniasis. Modulation of MHC class II gene products by keratinocytes before and after glucantime therapy

Epidermal changes from 32 cutaneous and 3 mucosal American cutaneous leishmaniasis (ACL) active lesions were studied for HLA-DR, -DQ and -DP expression, Langerhans cells and lymphocyte infiltration. In addition to a DR and DQ positivity at the surface of the cells of the inflammatory infiltrate, a strong reaction for DR antigens was detected on keratinocytes. Hyperplasia of Langerhans cells was present in all cutaneous lesions and epidermis was infiltrated by T lymphocytes. When healed lesions of 14 of these subjects were re-biopsied 1 to 12 months after the end of pentavalent antimonial therapy, MHC class II antigens could no longer be seen on keratinocytes. Our data represent evidence for the reversibility of the abnormal HLA-DR expression by keratinocytes in ACL after Glucantime therapy or spontaneous scar formation, demonstrating that this expression is restricted to the period of active lesions. The present findings can be regarded as an indirect evidence that keratinocytes may be involved in the immunopathology of ACL.     

Echocardiographic alterations in a child with cow's milk allergy: a case report

ABSTRACT: INTRODUCTION: Cow's milk allergy is the most frequent food allergy in Europe and western countries and shows a wide spectrum of clinical features, including atopic dermatitis and gastrointestinal disease. To the best of our knowledge, this report is the first to describe Kawasaki disease-like clinical features and echocardiographic alterations which resolved after a cow's milk-free diet. CASE PRESENTATION: We report a case of a 9-month-old Caucasian girl with atopic dermatitis who developed clinical features commonly present in Kawasaki disease (erythematous skin rash, non-exudative conjunctivitis, fissured lips and neck lymph nodes), together with mild echocardiographic alterations (perivascular brightness, pericardial effusion) in the absence of fever. These features resolved within 2 weeks after the beginning of a cow's milk-free diet. CONCLUSION: Kawasaki disease has recently been considered a possible risk factor for subsequent allergic disease secondary to immune dysfunction. This case report suggests that the immune-related alterations which are commonly present in allergic patients could be similar to the antigen-related immune response in Kawasaki disease and thus could lead to similar clinical features.