First Description of a Cluster of Acute/Subacute Paracoccidioidomycosis Cases and Its Association with a Climatic Anomaly

Background: Identifying clusters of acute paracoccidioidomycosis cases could potentially help in identifying the environmental factors that influence the incidence of this mycosis. However, unlike other endemic mycoses, there are no published reports of clusters of paracoccidioidomycosis. Methodology/Principal Findings: A retrospective cluster detection test was applied to verify if an excess of acute form (AF) paracoccidioidomycosis cases in time and/or space occurred in Botucatu, an endemic area in Sao Paulo State. The scan-test SaTScan v7.0.3 was set to find clusters for the maximum temporal period of 1 year. The temporal test indicated a significant cluster in 1985 (P<0.005). This cluster comprised 10 cases, although 2.19 were expected for this year in this area. Age and clinical presentation of these cases were typical of AF paracccidioidomycosis. The space-time test confirmed the temporal cluster in 1985 and showed the localities where the risk was higher in that year. The cluster suggests that some particularities took place in the antecedent years in those localities. Analysis of climate variables showed that soil water storage was atypically high in 1982/83 (similar to 2.11/2.5 SD above mean), and the absolute air humidity in 1984, the year preceding the cluster, was much higher than normal (similar to 1.6 SD above mean), conditions that may have favored, respectively, antecedent fungal growth in the soil and conidia liberation in 1984, the probable year of exposure. These climatic anomalies in this area was due to the 1982/83 El Nino event, the strongest in the last 50 years. Conclusions/Significance: We describe the first cluster of AF paracoccidioidomycosis, which was potentially linked to a climatic anomaly caused by the 1982/83 El Nino Southern Oscillation. This finding is important because it may help to clarify the conditions that favor Paracoccidioides brasiliensis survival and growth in the environment and that enhance human exposure, thus allowing the development of preventive measures.

Hypotheses, rationale, design, and methods for prognostic evaluation in type 2 diabetic patients with angiographically normal coronary arteries. The MASS IV-DM Trial

Background: The MASS IV-DM Trial is a large project from a single institution, the Heart Institute (InCor), University of Sao Paulo Medical School, Brazil to study ventricular function and coronary arteries in patients with type 2 diabetes mellitus. Methods/Design: The study will enroll 600 patients with type 2 diabetes who have angiographically normal ventricular function and coronary arteries. The goal of the MASS IV-DM Trial is to achieve a long-term evaluation of the development of coronary atherosclerosis by using angiograms and coronary-artery calcium scan by electron-beam computed tomography at baseline and after 5 years of follow-up. In addition, the incidence of major cardiovascular events, the dysfunction of various organs involved in this disease, particularly microalbuminuria and renal function, will be analyzed through clinical evaluation. In addition, an effort will be made to investigate in depth the presence of major cardiovascular risk factors, especially the biochemical profile, metabolic syndrome inflammatory activity, oxidative stress, endothelial function, prothrombotic factors, and profibrinolytic and platelet activity. An evaluation will be made of the polymorphism as a determinant of disease and its possible role in the genesis of micro- and macrovascular damage. Discussion: The MASS IV-DM trial is designed to include diabetic patients with clinically suspected myocardial ischemia in whom conventional angiography shows angiographically normal coronary arteries. The result of extensive investigation including angiographic follow-up by several methods, vascular reactivity, pro-thrombotic mechanisms, genetic and biochemical studies may facilitate the understanding of so-called micro- and macrovascular disease of DM.

Differential expression of 12 histone deacetylase (HDAC) genes in astrocytomas and normal brain tissue: class II and IV are hypoexpressed in glioblastomas

Background: Glioblastoma is the most lethal primary malignant brain tumor. Although considerable progress has been made in the treatment of this aggressive tumor, the clinical outcome for patients remains poor. Histone deacetylases (HDACs) are recognized as promising targets for cancer treatment. In the past several years, HDAC inhibitors (HDACis) have been used as radiosensitizers in glioblastoma treatment. However, no study has demonstrated the status of global HDAC expression in gliomas and its possible correlation to the use of HDACis. The purpose of this study was to evaluate and compare mRNA and protein levels of class I, II and IV of HDACs in low grade and high grade astrocytomas and normal brain tissue and to correlate the findings with the malignancy in astrocytomas. Methods: Forty-three microdissected patient tumor samples were evaluated. The histopathologic diagnoses were 20 low-grade gliomas (13 grade I and 7 grade II) and 23 high-grade gliomas (5 grade III and 18 glioblastomas). Eleven normal cerebral tissue samples were also analyzed (54 total samples analyzed). mRNA expression of class I, II, and IV HDACs was studied by quantitative real-time polymerase chain reaction and normalized to the housekeeping gene beta-glucuronidase. Protein levels were evaluated by western blotting. Results: We found that mRNA levels of class II and IV HDACs were downregulated in glioblastomas compared to low-grade astrocytomas and normal brain tissue (7 in 8 genes, p < 0.05). The protein levels of class II HDAC9 were also lower in high-grade astrocytomas than in low-grade astrocytomas and normal brain tissue. Additionally, we found that histone H3 (but not histone H4) was more acetylated in glioblastomas than normal brain tissue. Conclusion: Our study establishes a negative correlation between HDAC gene expression and the glioma grade suggesting that class II and IV HDACs might play an important role in glioma malignancy. Evaluation of histone acetylation levels showed that histone H3 is more acetylated in glioblastomas than normal brain tissue confirming the downregulation of HDAC mRNA in glioblastomas.

Hypothalamic-pituitary axis and peripheral tissue responses to TRH stimulation and Liothyronine suppression tests in normal subjects evaluated by current methods

Objective: To reevaluate the responses of thyrotropin-releasing hormone ( TRH) stimulation test in baseline condition as well as after the administration of graded supraphysiological doses of liothyronine ( L- T-3) in normal subjects. Design: To assess various parameters related to the hypothalamic-pituitary axis and peripheral tissue responses to L- T-3 in 22 normal individuals ( median age: 30.5 years). Subjects were submitted to an intravenous TRH test at baseline condition and also to the oral administration of sequential and graded doses of L- T-3 ( 50, 100, and 200 mu g/day), each given over 3 days, at an outpatient clinic. Blood samples were obtained for thyrotropin (TSH) and prolactin (PRL) at basal and then 15, 30, and 60 minutes after the TRH injection. Effects of L- T3 administration on cholesterol, creatine kinase, retinol, ferritin, and sex hormone-binding globulin ( SHBG) were also measured at basal and after the oral administration of L- T-3. Main outcome: TRH administration resulted in an increase of 4-to 14-fold rise in serum TSH ( 8.3 +/- 2.5-fold), and in a slight rise in serum PRL concentrations ( 3.8 +/- 1.5-fold). Administration of graded doses of triiodothyronine ( T-3) resulted in a dose-dependent suppression of TSH and PRL. Basal thyroxine- binding globulin (TBG) and cholesterol levels decreased, and ferritin and SHBG increased after L- T-3 administration, while creatine kinase and retinol did not change throughout the study. There was a positive correlation between basal TSH and TSH peak response to TRH at basal condition and after each sequential L- T-3 doses. On the other hand, TSH peak response to the TRH test did not predict cholesterol, TBG, ferritin, or SHBG values. Conclusion: Using the current methods on hormone and biochemical analysis, we standardized the response of many parameters to TRH stimulation test after sequential and graded T-3 suppression test in normal subjects. Our data suggest that the evaluation of the responses of the hypothalamus-pituitary axis to TRH test as well as the impact of L- T-3 on peripheral tissues were not modified by the current methods.

Soft tissue profile in white Brazilian adults with normal occlusions and well-balanced faces

Objective: To analyze anteroposterior soft tissue facial parameters for a sample of white Brazilian adults and to compare these measurements with the values proposed for white North American adults. Materials and Methods: Facial profile photographs were taken of 59 white Brazilians (30 men and 29 women) with normal occlusions and balanced faces with ages ranging from 18 to 30 years. The independent Student's t-test (P < .05) was used to compare the soft tissue parameters of the Brazilians with those of the North Americans. Results: White Brazilian women presented a less protruded face compared with white American women except for the glabella region. White Brazilian women showed a smaller nasal projection, less protruded upper and lower lips, a more obtuse nasolabial angle, and a smaller projection of the B' point and chin than white American women. Conversely, the two male groups demonstrated less evident soft tissue profile differences, with the exception of the nose projection, which was smaller in white Brazilian men than in white American men. Conclusions: A universal standard of facial esthetic is not applicable to diverse white populations. Differences regarding the soft tissue profile features were found between white Brazilians and white Americans. These differences should be considered in the orthodontic/orthognathic surgery diagnosis and treatment plan for white Brazilians together with the patient's individual opinion and perception of beauty.

Changes in temporomandibular joint disc position and form following Herbst and fixed orthodontic treatment

Objective: To determine the changes in the position and form of the temporomandibular joint articular disc in adolescents with Class II division 1 malocclusion and mandibular retrognathism treated with the Herbst appliance (phase I) and fixed orthodontic appliance (phase II). Materials and Methods: Thirty-two consecutive adolescents went through phase I of treatment and 23 completed phase II. The temporomandibular joints were evaluated qualitatively by means of magnetic resonance images at the beginning of treatment (T1), during phase I (T2), at the end of phase I (T3), and at the end of phase II (T4). Results: Significant changes in disc position were not observed with the mouth closed between T1 X T3 (P = .317), T3 X T4 (P = .287), or T1 X T4 (P = .261). At T2, on average, the disc was positioned regressively. With the mouth open, no difference was observed between T1 X T3 (P = .223) or T1 X T4 (P = .082). We did observe a significant difference between T3 X T4 (P < .05). Significant changes in the disc form were found with the mouth closed between T1 X T2 (P < .001) and T2 X T3 (P < .001). Conclusions: At the end of the two-phase treatment, in general terms, the position and form of the initial articular discs were maintained; however, in some temporomandibular joints some seemingly adverse effects were observed at T4. (Angle Orthod. 2010;80:843-852.)

Deletion of the Basement Membrane Heparan Sulfate Proteoglycan Type XVIII Collagen Causes Hypertriglyceridemia in Mice and Humans

Background: Lipoprotein lipase (Lpl) acts on triglyceride-rich lipoproteins in the peripheral circulation, liberating free fatty acids for energy metabolism or storage. This essential enzyme is synthesized in parenchymal cells of adipose tissue, heart, and skeletal muscle and migrates to the luminal side of the vascular endothelium where it acts upon circulating lipoproteins. Prior studies suggested that Lpl is immobilized by way of heparan sulfate proteoglycans on the endothelium, but genetically altering endothelial cell heparan sulfate had no effect on Lpl localization or lipolysis. The objective of this study was to determine if extracellular matrix proteoglycans affect Lpl distribution and triglyceride metabolism. Methods and Findings: We examined mutant mice defective in collagen XVIII (Col18), a heparan sulfate proteoglycan present in vascular basement membranes. Loss of Col18 reduces plasma levels of Lpl enzyme and activity, which results in mild fasting hypertriglyceridemia and diet-induced hyperchylomicronemia. Humans with Knobloch Syndrome caused by a null mutation in the vascular form of Col18 also present lower than normal plasma Lpl mass and activity and exhibit fasting hypertriglyceridemia. Conclusions: This is the first report demonstrating that Lpl presentation on the lumenal side of the endothelium depends on a basement membrane proteoglycan and demonstrates a previously unrecognized phenotype in patients lacking Col18.

Normal and defective mariner-like elements in Rhynchosciara species (Sciaridae, Diptera)

Mariner-like elements are widely present in diverse organisms. These elements constitute a large fraction of the eukaryotic genome; they transpose by a ""cut-and-paste"" mechanism with their own transposase protein. We found two groups of mobile elements in the genus Rhynchosciara. PCR using primers designed from R. americana transposons (Ramar1 and Ramar2) were the starting point for this comparative study. Genomic DNA templates of four species: R. hollaenderi, R. millerii, R. baschanti, and Rhynchosciara sp were used and genomic sequences were amplified, sequenced and the molecular structures of the elements characterized as being putative mariner-like elements. The first group included the putative full-length elements. The second group was composed of defective mariner elements that contain a deletion overlapping most of the internal region of the transposase open reading frame. They were named Rmar1 (type 1) and Rmar2 (type 2), respectively. Many conserved amino acid blocks were identified, as well as a specific D,D(34) D signature motif that was defective in some elements. Based on predicted transposase sequences, these elements encode truncated proteins and are phylogenetically very close to mariner-like elements of the mauritiana subfamily. The inverted terminal repeat sequences that flanked the mariner-like elements are responsible for their mobility. These inverted terminal repeat sequences were identified by inverse PCR.

Dispersive analysis of KL mu 3 and KLe3 scalar and vector form factors using KTeV data

Using the published KTeV samples of K(L) -> pi(+/-)e(-/+)nu and K(L) -> pi(+/-)mu(-/+)nu decays, we perform a reanalysis of the scalar and vector form factors based on the dispersive parametrization. We obtain phase-space integrals I(K)(e) = 0.15446 +/- 0.00025 and I(K)(mu) = 0.10219 +/- 0.00025. For the scalar form factor parametrization, the only free parameter is the normalized form factor value at the Callan-Treiman point (C); our best-fit results in InC = 0.1915 +/- 0.0122. We also study the sensitivity of C to different parametrizations of the vector form factor. The results for the phase-space integrals and C are then used to make tests of the standard model. Finally, we compare our results with lattice QCD calculations of F(K)/F(pi) and f(+)(0).

Multimode Vibrational Couplings in Resonant Positron Annihilation

The mechanisms for multimode vibrational couplings in resonant positron annihilation are not well understood. We show that these resonances can arise from positron-induced distortions of the potential energy surface (target response to the positron field). Though these distortions can transfer energy into single- and multiquantum vibrations, they have so far been disregarded as a pathway to resonant annihilation. We also compare the existing annihilation theories and show that the currently accepted model can be cast as a special case of the Feshbach annihilation theory.

Magnetic resonant x-ray diffraction study of europium telluride

Here we use magnetic resonant x-ray diffraction to study the magnetic order in a 1.5 mu m EuTe film grown on (111) BaF(2) by molecular-beam epitaxy. At Eu L(II) and L(III) absorption edges, a resonant enhancement of more than two orders was observed for the sigma ->pi(') diffracted intensity at half-order reciprocal-lattice points, consistent with the magnetic character of the scattering. We studied the evolution of the (1/21/21/2) magnetic reflection with temperature. When heating toward the Neel temperature (T(N)), the integrated intensity decreased monotonously and showed no hysteresis upon cooling again, indicating a second-order phase transition. A power-law fit to the magnetization versus temperature curve yielded T(N)=9.99(1) K and a critical exponent beta=0.36(1), which agrees with the renormalization theory results for three-dimensional Heisenberg magnets. The fits to the sublattice magnetization dependence with temperature, disregarding and considering fourth-order exchange interactions, evidenced the importance of the latter for a correct description of magnetism in EuTe. A value of 0.009 was found for the (2j(1)+j(2))/J(2) ratio between the Heisenberg J(2) and fourth-order j(1,2) exchange constants. The magnetization curve exhibited a round-shaped region just near T(N) accompanied by an increase in the magnetic peak width, which was attributed to critical scattering above T(N). The comparison of the intensity ratio between the (1/21/21/2) and the (1/21/21/2) magnetic reflections proved that the Eu(2+) spins align within the (111) planes, and the azimuthal dependence of the (1/21/21/2) magnetic peak is consistent with the model of equally populated S domains.

Magnetic ordering of EuTe/PbTe multilayers determined by x-ray resonant diffraction

In this work we use resonant x-ray diffraction combined with polarization analysis of the diffracted beam to study the magnetic ordering in EuTe/PbTe multilayers. The presence of satellites at the (1/2 1/2 1/2) magnetic reflection of a 50 /repetition EuTe/PbTe superlattice demonstrated the existence of magnetic correlations among the alternated EuTe layers. The behavior of the satellites intensity as T increases toward the Neel temperature T(N) indicates that these correlations persist nearly up to T(N) and suggests the preferential decrease of the magnetic order parameter of external monolayers of each EuTe layer within the superlattice. (C) 2008 American Institute of Physics.

Limit on the diffuse flux of ultrahigh energy tau neutrinos with the surface detector of the Pierre Auger Observatory

Data collected at the Pierre Auger Observatory are used to establish an upper limit on the diffuse flux of tau neutrinos in the cosmic radiation. Earth-skimming nu(tau) may interact in the Earth's crust and produce a tau lepton by means of charged-current interactions. The tau lepton may emerge from the Earth and decay in the atmosphere to produce a nearly horizontal shower with a typical signature, a persistent electromagnetic component even at very large atmospheric depths. The search procedure to select events induced by tau decays against the background of normal showers induced by cosmic rays is described. The method used to compute the exposure for a detector continuously growing with time is detailed. Systematic uncertainties in the exposure from the detector, the analysis, and the involved physics are discussed. No tau neutrino candidates have been found. For neutrinos in the energy range 2x10(17) eV < E(nu)< 2x10(19) eV, assuming a diffuse spectrum of the form E(nu)(-2), data collected between 1 January 2004 and 30 April 2008 yield a 90% confidence-level upper limit of E(nu)(2)dN(nu tau)/dE(nu)< 9x10(-8) GeV cm(-2) s(-1) sr(-1).

Characterization of global transcription profile of normal and HPV-immortalized keratinocytes and their response to TNF treatment

Background: Persistent infection by high risk HPV types (e.g. HPV-16, -18, -31, and -45) is the main risk factor for development of cervical intraepithelial neoplasia and cervical cancer. Tumor necrosis factor (TNF) is a key mediator of epithelial cell inflammatory response and exerts a potent cytostatic effect on normal or HPV16, but not on HPV18 immortalized keratinocytes. Moreover, several cervical carcinoma-derived cell lines are resistant to TNF anti-proliferative effect suggesting that the acquisition of TNF-resistance may constitute an important step in HPV-mediated carcinogenesis. In the present study, we compared the gene expression profiles of normal and HPV16 or 18 immortalized human keratinocytes before and after treatment with TNF for 3 or 60 hours. Methods: In this study, we determined the transcriptional changes 3 and 60 hours after TNF treatment of normal, HPV16 and HPV18 immortalized keratinocytes by microarray analysis. The expression pattern of two genes observed by microarray was confirmed by Northern Blot. NF-kappa B activation was also determined by electrophoretic mobility shift assay (EMSA) using specific oligonucleotides and nuclear protein extracts. Results: We observed the differential expression of a common set of genes in two TNF-sensitive cell lines that differs from those modulated in TNF-resistant ones. This information was used to define genes whose differential expression could be associated with the differential response to TNF, such as: KLK7 (kallikrein 7), SOD2 (superoxide dismutase 2), 100P (S100 calcium binding protein P), PI3 (protease inhibitor 3, skin-derived), CSTA (cystatin A), RARRES1 (retinoic acid receptor responder 1), and LXN (latexin). The differential expression of the KLK7 and SOD2 transcripts was confirmed by Northern blot. Moreover, we observed that SOD2 expression correlates with the differential NF-kappa B activation exhibited by TNF-sensitive and TNF-resistant cells. Conclusion: This is the first in depth analysis of the differential effect of TNF on normal and HPV16 or HPV18 immortalized keratinocytes. Our findings may be useful for the identification of genes involved in TNF resistance acquisition and candidate genes which deregulated expression may be associated with cervical disease establishment and/or progression.

A note on the likelihood and moments of the skew-normal distribution

In this paper an alternative approach to the one in Henze (1986) is proposed for deriving the odd moments of the skew-normal distribution considered in Azzalini (1985). The approach is based on a Pascal type triangle, which seems to greatly simplify moments computation. Moreover, it is shown that the likelihood equation for estimating the asymmetry parameter in such model is generated as orthogonal functions to the sample vector. As a consequence, conditions for a unique solution of the likelihood equation are established, which seem to hold in more general setting.