Wild animals as sentinels of Paracoccidioides brasiliensis in the state of Rio Grande do Sul, Brazil.

Paracoccidioides brasiliensis, a dimorphic pathogenic fungus, causes the principal form of systemic mycosis in Brazil. The literature furnishes only limited data on the ecology of this fungus in the state of Rio Grande do Sul, the southernmost state of Brazil. The purpose of this study was to evaluate the prevalence of fungal infection in wild animals, using serological tests and using the animals as sentinels of the presence of P. brasiliensis in three specified mesoregions of Rio Grande do Sul. A total of 128 wild animals from the three mesoregions were included in the study. The serum samples were evaluated by immunodiffusion and the enzyme-linked immunosorbent assay (ELISA) technique to detect anti-gp43 antibodies from P. brasiliensis. Two conjugates were tested and compared with the ELISA technique. Although no positive samples were detected by immunodiffusion, 26 animals (20%), belonging to 13 distinct species, were found to be seropositive by the ELISA technique. The seropositive animals were from two mesoregions of the state. The results were similar according to the gender, age, and family of the animals, but differed significantly according to the conjugate used (p < 0.001), showing more sensitivity to protein A-peroxidase than to protein G-peroxidase. The finding that wild animals from the state of Rio Grande do Sul are exposed to P. brasiliensis suggests that the fungus can be found in this region despite the often-rigorous winters, which frequently include below-freezing temperatures.

[A retrospective analysis comparing colposuspension and retropubic mid-urethral sling as preventive anti-incontinence measures during laparoscopic sacrocolpopexy]. / Analisi retrospettiva di confronto tra colposospensione e sling retropubica medio-uretrale come misure preventive anti-incontinenza in corso di sacrocolpopessia laparoscopica.

AIM: The aim of this paper was to compare two anti-incontinence procedures during laparoscopic sacrocolpopexy (LSC) to prevent postoperative stress urinary incontinence (SUI). METHODS: Retrospective analysis of 90 continent hysterectomized patients with vaginal vault prolapse treated with LSC plus colposuspension (group A, N.=30), LSC plus retropubic mid-urethral sling (group B, N.=30), or LSC alone (group C, N.=30). RESULTS: De novo SUI rate resulted significantly (P<0.05) lower in group B than C. No difference was detected regarding de novo urge urinary incontinence. Total reoperation rate resulted significantly (P<0.05) higher in group A than B and lower in group B than C. CONCLUSION: When associated to LSC for preventing SUI, colposuspension and retropubic mid-urethral sling are effective and safe, even if mid-urethral sling seems to provide the best risk/benefit profile.

[Sex ratio in the offspring of pregnant women with polycystic ovary syndrome: effect of different phenotypes]. / Sex ratio nella prole di donne affette dalla sindrome dell'ovaio policistico: effetti dei differenti fenotipi.

AIM: The aim of this paper was to investigate the sex ratio in the offspring of pregnant patients with polycystic ovary syndrome (PCOS). METHODS: Analysis of 70 pregnant patients with PCOS who achieve a pregnancy without any kind of treatment, and having as controls 63 healthy pregnant women without any feature of PCOS. RESULTS: No significant difference in sex ratio was detected between PCOS and controls, even if it resulted significantly different in the full-blown and non-PCO phenotypes. CONCLUSION: The PCOS phenotypes influenced the sex ratio in the offspring, suggesting that environmental factors could play a role in determination of the offspring gender.

Simulation of pandemics in real cities: enhanced and accurate digital laboratories.

This study develops a modelling framework for simulating the spread of infectious diseases within real cities. Digital copies of Birmingham (UK) and Bogotá (Colombia) are generated, reproducing their urban environment, infrastructure and population. The digital inhabitants have the same statistical features of the real population. Their motion is a combination of predictable trips (commute to work, school, etc.) and random walks (shopping, leisure, etc.). Millions of individuals, their encounters and the spread of the disease are simulated by means of high-performance computing and massively parallel algorithms for several months and a time resolution of 1 minute. Simulations accurately reproduce the COVID-19 data for Birmingham and Bogotá both before and during the lockdown. The model has only one adjustable parameter calculable in the early stages of the pandemic. Policymakers can use our digital cities as virtual laboratories for testing, predicting and comparing the effects of policies aimed at containing epidemics.

Statistical validation of mutual information calculations: comparison of alternative numerical algorithms.

Given two time series X and Y , their mutual information, I (X,Y) = I (Y,X) , is the average number of bits of X that can be predicted by measuring Y and vice versa. In the analysis of observational data, calculation of mutual information occurs in three contexts: identification of nonlinear correlation, determination of an optimal sampling interval, particularly when embedding data, and in the investigation of causal relationships with directed mutual information. In this contribution a minimum description length argument is used to determine the optimal number of elements to use when characterizing the distributions of X and Y . However, even when using partitions of the X and Y axis indicated by minimum description length, mutual information calculations performed with a uniform partition of the XY plane can give misleading results. This motivated the construction of an algorithm for calculating mutual information that uses an adaptive partition. This algorithm also incorporates an explicit test of the statistical independence of X and Y in a calculation that returns an assessment of the corresponding null hypothesis. The previously published Fraser-Swinney algorithm for calculating mutual information includes a sophisticated procedure for local adaptive control of the partitioning process. When the Fraser and Swinney algorithm and the algorithm constructed here are compared, they give very similar numerical results (less than 4% difference in a typical application). Detailed comparisons are possible when X and Y are correlated jointly Gaussian distributed because an analytic expression for I (X,Y) can be derived for that case. Based on these tests, three conclusions can be drawn. First, the algorithm constructed here has an advantage over the Fraser-Swinney algorithm in providing an explicit calculation of the probability of the null hypothesis that X and Y are independent. Second, the Fraser-Swinney algorithm is marginally the more accurate of the two algorithms when large data sets are used. With smaller data sets, however, the Fraser-Swinney algorithm reports structures that disappear when more data are available. Third, the algorithm constructed here requires about 0.5% of the computation time required by the Fraser-Swinney algorithm.

Hyaluronic acid-chondroitin sulfate: a potential factor to select pure stress urinary incontinence in patients with interstitial cystitis/painful bladder syndrome and mixed incontinence symptoms.

AIM: Aim of the study was to validate the Hyaluronic acid-Chondroitin sulfate (HA-CS) as ex adiuvantibus criteria to identified patients with urgency symptoms related to interstitial cystitis/painful bladder syndrome (IC/PBS) and to obtained a population of patients with pure stress urinary incontinence. METHODS: We retrospectively analysed clinical data of 17 patients with clinical suspect of IC/PBS, which received intravescical HA-CS to reduce pelvic pain and urgency symptoms waiting for surgical treatment for stress urinary incontinence. The main outcomes were reduction of urinary frequency, urgency, and bladder pain. RESULTS: Compared to baseline, a significant decrease in pain, urgency and frequency were observed. Of the 17 patients, 82.3% reported resolution of pain and urge symptoms and in patients with persistence of urge symptoms the urodynamic assessment showed an overactive bladder syndrome (OAB). CONCLUSION: HA-CS treatment induces an improvement in pain and urgency symptoms in patients with IC/PBS that referred also stress urinary incontinence. Therefore, HA-CS treatment could be use as clinical adjunctive parameter to select patients with pure stress urinary incontinence.

Acute oxygen supplementation does not relieve the impairment of respiratory muscle strength in hypoxemic COPD.

STUDY OBJECTIVES: To verify whether hypoxemia affects respiratory muscle strength in the absence of malnutrition and whether such effect, if present, is reversible with an acute oxygen supplementation. DESIGN: Case series analysis, before-after trial. SETTING: Outpatient pneumology departments of two university hospitals. PATIENTS: One hundred twenty patients affected by COPD in stable conditions having actual to ideal body weight ratio of > or =90%. MEASUREMENTS AND RESULTS: Maximal inspiratory pressure (MIP) was measured at functional residual capacity level in the whole sample of subjects and during oxygen supplementation in 58 patients having a PaO2< or =60 mm Hg when breathing in room air. Predictors of MIP were assessed by a multivariate analysis. MIP values before and after oxygen supplementation were compared by a paired t test. MIP was independently correlated with FVC (p<0.001), PaO2 (p<0.01), and age (p<0.01). In the subgroup of hypoxemic patients, MIP values did not change significantly after oxygen supplementation (3.08+/-1.74 vs 3.03+/-1.91 kPa, t=0.43, not significant). CONCLUSIONS: Hypoxemia is an important negative correlate of MIP even in well-nourished COPD patients. Its effect is not reversible with an acute oxygen supplementation.

Cognitive-behavioral group therapy for social phobia in female adolescents: results of a pilot study.

OBJECTIVES: To examine the efficacy of cognitive-behavioral group therapy for adolescents (CBGT-A) in females with social phobia and the effect of this treatment on the risk for major depression. METHOD: Female adolescents with social phobia (N = 35) were randomly assigned to treatment (n = 12) or no treatment (n = 23) groups. Assessments were conducted at baseline, after treatment, and at a 1-year follow-up. RESULTS: Eleven subjects completed treatment. Sixteen weeks of treatment produced a significant improvement in interference and reduction in symptoms of social anxiety. There was a significant reduction in the number of subjects meeting DSM-IV criteria for social phobia in the CBGT-A versus the untreated group; however, at the 1-year follow-up there were no significant differences by treatment condition. There was also suggestive evidence that treatment of social phobia lowers the risk for relapse of major depression among those with a history of major depression. Combining social phobia and major depression as the outcome produced more robust treatment effects in the 1-year follow-up. CONCLUSIONS: This pilot study provides evidence for a moderate short-term effect of CBGT-A for treating female adolescents suffering from social phobia and indicates that treatment of social phobia may result in a reduction of major depression.

Screening for anxiety and depression in early adolescence.

OBJECTIVE: To examine the level of diagnostic and discriminative accuracy of three dimensional rating scales for detecting anxiety and depressive disorders in a school-based survey of 9th grade youths. METHOD: Classroom screening instruments, the Center for Epidemiologic Studies-Depression Scale (CES-D), the Revised Children's Manifest Anxiety Scale (RCMAS), and the Multidimensional Anxiety Scale for Children (MASC) were administered to 632 youths from three sites in 1998. On the basis of rating scale results, samples of high-scoring and non-high-scoring youths were invited to participate in a diagnostic interview conducted within 2 months of the screening sessions. RESULTS: MASC scores were most strongly associated with individual anxiety disorders, particularly among females, whereas the CES-D composite score was associated with a diagnosis of major depression, after controlling for comorbid disorders. The RCMAS was least successful in discriminating anxiety and depression. When receiver operator characteristic curves were examined, diagnostic accuracy was moderate. CONCLUSIONS: The ability of the MASC and CES-D to discriminate within and between categorically defined diagnostic groups has important implications for the accurate identification of youths in need of services.

Action of cystine in the cytotoxic response of Escherichia coli cells exposed to hydrogen peroxide.

Cystine markedly enhanced the cytotoxic response of Escherichia coli cells to concentrations of hydrogen peroxide resulting in mode one killing, but displayed little effect in mode two killed cells. The effect of cystine was concentration-dependent over a range of 5-50 microM and did not further increase at higher levels. Cystine had similar effects in other bacterial systems. In order to sensitize the cells to the oxidative injury, the amino acid must be present during exposure to the oxidant since no enhancement of the cytotoxic response can be observed in cystine pre-loaded cells. In addition, no further enhancement of cytotoxicity could be detected when cystine was added before and left during challenge with the oxidant. The enhancing effect of cystine on oxidative injury of E. coli cells appears to be directly mediated by the amino acid and in fact cysteic acid, the most likely oxidation product, had no effect on the killing of bacterial cells elicited by hydrogen peroxide. Other disulfide compounds such as oxidized glutathione, cystamine and dithionitrobenzoic acid only slightly increased the susceptibility of bacteria to the oxidant. The effect of the disulfides was not concentration-dependent over a range of 200-800 microM and was statistically significant only for cystamine. Taken together, these results indicate that cystine markedly increases the cytotoxic response of bacteria to hydrogen peroxide and suggest that the amino acid might impair the cellular defence machinery against hydrogen peroxide. This effect may involve a thiol-disulfide exchange reaction at the cell membrane level.

The structure of negative emotions in a clinical sample of children and adolescents.

The authors sought to define the latent factors associated with childhood anxiety and depression, using a structural equations/confirmatory factor-analytic approach involving multiple informants (i.e., parent and child report) of symptoms. A sample of 216 children and adolescents with diagnoses of an anxiety disorder or comorbid anxiety and mood disorders and their parents were administered measures of childhood fear, anxiety, and depression. Results of comparative modeling best supported 3-factor solutions (fear, anxiety, and depression) that were consistent with recent conceptual models of anxiety and depression (e.g., tripartite model). Results also suggested that 3 widely used measures of childhood negative emotion are conceptually heterogeneous (containing item sets that loaded on different latent factors). Implications for the assessment of childhood negative emotions are discussed.

Treatment of anxiety disorders of childhood.

The development of empirically derived, efficacious treatment methods for the range of anxiety disorders in children and adolescents lags far behind the field of adult anxiety treatment research. Controlled trials of both psychosocial and pharmacologic methods are warranted, and several trials are currently underway. Although the literature in this field is growing, many questions remain regarding the application and long-term benefit of interventions with youth. Specifically, although the field of adult psychosocial treatment research has advanced such that empirically derived treatment protocols are readily available, such methodologies are lacking for anxious youth. Serious attention must turn toward the empirical testing and validation of developmentally appropriate psychosocial treatment protocols. Fortunately, work in this area is currently under way in several centers (e.g., for social phobia, OCD, and generalized anxiety). Moreover, the role of parents in the psychosocial treatment process remains largely unexplored. Investigations are underway examining the effectiveness of training parents in the delivery of particular psychosocial procedures and evaluating the optimal "degree" of parental involvement. Attention also must turn to the systematic study of variables hypothesized to affect negatively the successful integration of parents (e.g., age of child, severity of disorder, parental psychopathology). And lastly, combined trials of pharmacologic compounds and psychosocial interventions are needed to examine the prescriptive treatment approach of matching patients to treatments.

Increased microbicidal activity of human monoblastoid cells upon long-term exposure to dideoxycytidine.

2',3'-Dideoxycytidine (ddC) is a nucleoside analogue currently used in AIDS therapy. We had previously found that long term exposure of U937 human monoblastoid cells to ddC induces the selection of drug-resistant cells (U937-R). In the present work we investigated some important biochemical properties and functional activities of these resistant cells. The results obtained show that U937-R maintained the properties of cell aggregation, adhesion and differentiation. Basal respiration, protein kinase C activity, superoxide anion release and intracellular free calcium were all increased in the drug-resistant line. Phagocytosis of fungi (Candida albicans) and bacteria (Staphylococcus aureus and Salmonella anatum) were similar in U937 and U937-R cells. Killing of C. albicans was significantly higher in drug-resistant cells (29.07 +/- 2.23% of killing vs 19.07 +/- 2.01 in the control; p < 0.001). Similarly, the bacterial killing was enhanced in U937-R cells (34.07 +/- 8.06% vs 22.60 +/- 4.41% in the control; p < 0.05). Thus, the results presented in this paper provide evidence of an increased microbicidal activity of human monocytic cells upon long term exposure to ddC, most likely due to an increased oxidative metabolism.

Lethality of hydrogen peroxide in wild type and superoxide dismutase mutants of Escherichia coli. (A hypothesis on the mechanism of H2O2-induced inactivation of Escherichia coli).

The toxicity of H2O2 in Escherichia coli wild type and superoxide dismutase mutants was investigated under different experimental conditions. Cells were either grown aerobically, and then treated in M9 salts or K medium, or grown anoxically, and then treated in K medium. Results have demonstrated that the wild type and superoxide dismutase mutants display a markedly different sensitivity to both modes of lethality produced by H2O2 (i.e. mode one killing, which is produced by concentrations of H2O2 lower than 5 mM, and mode two killing which results from the insult generated by concentrations of H2O2 higher than 10 mM). Although the data obtained do not clarify the molecular basis of H2O2 toxicity and/or do not explain the specific function of superoxide ions in H2O2-induced bacterial inactivation, they certainly demonstrate that the latter species plays a key role in both modes of H2O2 lethality. A mechanism of H2O2 toxicity in E. coli is proposed, involving the action of a hypothetical enzyme which should work as an O2-. generating system. This enzyme should be active at low concentrations of H2O2 (less than 5 mM) and high concentrations of the oxidant (greater than 5 mM) should inactivate the same enzyme. Superoxide ions would then be produced and result in mode one lethality. The resistance at intermediate H2O2 concentrations may be dependent on the inactivation of such enzyme with no superoxide ions being produced at levels of H2O2 in the range 5-10 mM. Mode two killing could be produced by the hydroxyl radical in concert with superoxide ions, chemically produced via the reaction of high concentrations of H2O2 (greater than 10 mM) with hydroxyl radicals. The rate of hydroxyl radical production may be increased by the higher availability of Fe2+ since superoxide ions may also reduce trivalent iron to the divalent form.

In vitro and in vivo toxicity of 2',3'-dideoxycytidine in mice.

3T3 mouse embryo fibroblast cell growth was inhibited in a concentration dependent manner by 2',3'-dideoxycytidine (ddCyd), a strong inhibitor of human immunodeficiency virus. Cell growth inhibition was associated with an increased incorporation of ddCyd into cell DNA. In contrast SP2/0-Ag14 (a mouse myeloma) cell growth is not inhibited by 100 microM ddCyd both in the presence or absence of hypoxanthine and thymidine. Furthermore, in vitro spleen cell proliferation, upon phytohemagglutinin (PHA) addition, was much more affected by ddCyd in C57BL/6 mice than in Swiss albino mice. That indeed ddCyd affects spleen cell proliferation was confirmed by studies on splenocytes obtained from C57BL/6 mice that received ddCyd for 2 weeks in drinking water. These results suggest that ddCyd toxicity in mice is cell and strain dependent and that the toxicity mechanism is related to the incorporation of the drug in cell DNA.

In vitro toxicity and metabolism of 2',3'-dideoxycytidine, an inhibitor of human immunodeficiency virus infectivity.

U937 human monoblastoid cell growth was inhibited in a concentration-dependent manner by 2',3'-dideoxycytidine (ddCyd) (an antiretroviral drug) up to 500 microM. Cell growth inhibition was associated with a pronounced increase in cell volume, however this was not due to cell ATP or NAD+ depletion that could effect osmotic balance or DNA repair. This ddCyd toxicity paralleled the accumulation of ddCyd into acid soluble material where 2',3'-dideoxycytidine-5'-triphosphate (ddCTP) was the predominant labelled nucleotide up to an extracellular ddCyd concentration of 150 microM. At higher ddCyd concentrations, the amount of 2',3'-dideoxycytidine-5'-diphosphate (ddCDP) became predominant over ddCTP. This increase of phosphorylated dideoxycytidine in U937 cells was also associated with an increased incorporation of the drug into cell DNA suggesting a possible toxicity mechanism. That ddCyd does indeed become cytotoxic to human cell by incorporation into DNA was shown by incubating human resting and stimulated lymphocytes with ddCyd. While the drug does not affect cell viability in resting cells it strongly affects cell proliferation upon phytohemagglutinin (PHA) addition.

Differential effect of the amino acid cystine in cultured mammalian and bacterial cells exposed to oxidative stress.

The effect of cystine in the cytotoxic response of cultured Chinese hamster ovary and Escherichia coli cells to challenge with hydrogen peroxide has been investigated. It was found that this amino acid could either protect or sensitize cells, depending on the cellular system. In fact, although a reduction in the growth-inhibitory effect of hydrogen peroxide was observed in mammalian cells, a marked increase in the susceptibility to oxidative stress was induced by cystine in bacteria. None of the amino acid precursors of glutathione, e.g., glutamate, glycine or cysteine, afforded protection in the mammalian cell system, whereas cysteine, but not glycine or glutamate, markedly sensitized bacteria to hydrogen peroxide-induced cell killing. In mammalian cells, methionine, an amino acid which is converted to cysteine, was also unable to modify the oxidative response. The results presented indicate that cystine displays differential effects in oxidatively injured mammalian or bacterial cells and suggest that the mechanism whereby the amino acid modulates the lethal action of hydrogen peroxide differs in the two cellular systems.

Comment on "Performance of different synchronization measures in real data: a case study on electroencephalographic signals".

Quian Quiroga et al. [Phys. Rev. E 65, 041903 (2002)] reported a similar performance of several linear and nonlinear measures of synchronization when applied to the rat electrocorticogram (ECoG). However, they found that the mutual information measure did not produce robust estimates of synchronization when compared to other measures. We reexamined their data using a histogram method with adaptive partitioning and found the mutual information to be a useful measure of regional ECoG interdependence.

Comparative study of embedding methods.

Embedding experimental data is a common first step in many forms of dynamical analysis. The choice of appropriate embedding parameters (dimension and lag) is crucial to the success of the subsequent analysis. We argue here that the optimal embedding of a time series cannot be determined by criteria based solely on the time series itself. Therefore we base our analysis on an examination of systems that have explicit analytic representations. A comparison of analytically obtained results with those obtained by an examination of the corresponding time series provides a means of assessing the comparative success of different embedding criteria. The assessment also includes measures of robustness to noise. The limitations of this study are explicitly delineated. While bearing these limitations in mind, we conclude that for the examples considered here, the best identification of the embedding dimension was achieved with a global false nearest neighbors argument, and the best value of lag was identified by the mutual information function.

Comparison of colloidal bismuth subcitrate and metronidazole, both in combination with an H2-antagonist as therapy for Helicobacter pylori.

In this random study, the efficacy of either colloidal bismuth subcitrate (CBS) or metronidazole in combination with an H2-antagonist in the treatment of various gastric pathologies was evaluated, along with the trends in antibody levels. Among the 40 Helicobacter pylori-positive patients with various gastroduodenal pathologies who underwent chemotherapy, 27 were treated with CBS and 13 with metronidazole. H. pylori was eradicated in 48.14% of the patients treated with CBS and 53.8% of those treated with metronidazole. After therapy, no statistically significant or slight decrease in the serum levels of antibodies was found.