Attempts to Improve Xenodiagnosis: Comparative Test of Sensibility Using Rhodnius neglectus, Panstrongylus megistus, Triatoma vitticeps and Triatoma infestans in Endemic Areas of Brazil

From June 1984 to July 1992, 392 xenodiagnostic tests were applied on 264 patients with chronic Chagas disease from Brazilian endemic areas of Virgem da Lapa and Coronel Murta, situated in the Jequitinhonha Valley, in the State of Minas Gerais. The susceptibilities of Rhodnius neglectus, Panstrongylus megistus, Triatoma vitticeps and Triatoma infestans were compared. Most of the time 20 nymphs (fourth instar) of each species were applied to 161 women and 103 men aged between 5 and 83 years of age. The tests were prepared to compare the susceptibilities of two species at a time, using the same patients for each test. Results showed a xenopositiveness of 26.28% (103 tests) being 27.98% in women (68 positive in 243 applied tests) and 23.49% in men (35 positive in 149 applied tests). The relative frequency of xenopositiveness displayed a great superiority of P. megistus and T. vitticeps. In tests from type I, for example, P. megistus was the unique responsible for 10.73% of positive xenodiagnosis vs. only 0.98% in T. infestans. Other parameters analized in this work confirm this superiority, and corroborate that T. infestans can be replaced by P. megistus and /or T. vitticeps in order to upgrade the efficacy of xenodiagnosis

Characteristic bimodal profiles of RNA polymerase II at thousands of active mammalian promoters.

BACKGROUND: In mammals, ChIP-seq studies of RNA polymerase II (PolII) occupancy have been performed to reveal how recruitment, initiation and pausing of PolII may control transcription rates, but the focus is rarely on obtaining finely resolved profiles that can portray the progression of PolII through sequential promoter states. RESULTS: Here, we analyze PolII binding profiles from high-coverage ChIP-seq on promoters of actively transcribed genes in mouse and humans. We show that the enrichment of PolII near transcription start sites exhibits a stereotypical bimodal structure, with one peak near active transcription start sites and a second peak 110 base pairs downstream from the first. Using an empirical model that reliably quantifies the spatial PolII signal, gene by gene, we show that the first PolII peak allows for refined positioning of transcription start sites, which is corroborated by mRNA sequencing. This bimodal signature is found both in mouse and humans. Analysis of the pausing-related factors NELF and DSIF suggests that the downstream peak reflects widespread pausing at the +1 nucleosome barrier. Several features of the bimodal pattern are correlated with sequence features such as CpG content and TATA boxes, as well as the histone mark H3K4me3. CONCLUSIONS: We thus show how high coverage DNA sequencing experiments can reveal as-yet unnoticed bimodal spatial features of PolII accumulation that are frequent at individual mammalian genes and reminiscent of transcription initiation and pausing. The initiation-pausing hypothesis is corroborated by evidence from run-on sequencing and immunoprecipitation in other cell types and species.

Electro-cortical correlates of motor inhibition : a comparison between selective and non-selective stop tasks

In this study, we compared a selective stop task (transition from a bimanual in-phase to a unimanual index fingers' tapping), with a non-selective stop task (stopping a bimanual in-phase tapping at all), and with a switching task (transition from in-phase to anti-phase bimanual tapping). The aim was twofold: 1) to identify the electro-cortical correlates of selective and non-selective inhibition processes and 2) to investigate which type of inhibition - selective or not - is required when switching between two bimanual motor patterns. The results revealed that all tasks led to enhanced activation (alpha power) of the left sensorimotor and posterior regions which seems to reflect an overall effort to stop the preferred bimanual in-phase tendency. Each task implied specific functional connectivity reorganizations (beta coherence) between cerebral motor areas, probably reflecting engagement in a new unimanual or bimanual movement.

Predictors of HIV-protection behaviour in HIV-positive men who have sex with casual male partners: a test of the explanatory power of an extended Information-Motivation-Behavioural Skills model.

This prospective study applies an extended Information-Motivation-Behavioural Skills (IMB) model to establish predictors of HIV-protection behaviour among HIV-positive men who have sex with men (MSM) during sex with casual partners. Data have been collected from anonymous, self-administered questionnaires and analysed by using descriptive and backward elimination regression analyses. In a sample of 165 HIV-positive MSM, 82 participants between the ages of 23 and 78 (M=46.4, SD=9.0) had sex with casual partners during the three-month period under investigation. About 62% (n=51) have always used a condom when having sex with casual partners. From the original IMB model, only subjective norm predicted condom use. More important predictors that increased condom use were low consumption of psychotropics, high satisfaction with sexuality, numerous changes in sexual behaviour after diagnosis, low social support from friends, alcohol use before sex and habitualised condom use with casual partner(s). The explanatory power of the calculated regression model was 49% (p<0.001). The study reveals the importance of personal and social resources and of routines for condom use, and provides information for the research-based conceptualisation of prevention offers addressing especially people living with HIV ("positive prevention").

Direct Sensitivity Test of the MB/BacT System

In order to evaluate the direct-method test of sensitivity to drugs used in the principal tuberculosis treatment regimes, in the Organon Teknika MB/BacT system, we tested 50 sputum samples positive to microscopy taken from patients with pulmonary tuberculosis and with clinical indications for an antibiogram, admitted sequentially for examination during the routine of the reference laboratory. The material was treated v/v with 23% trisodium phosphate solution, incubated for 24 h at 35°C, and neutralized v/v with 20% monosodium phosphate solution. The material was then centrifuged and the sediment inoculated into flasks containing Rifampin - 2 µg/ml, Isoniazid - 0.2 µg/ml, Pyrazinamide - 100 µg/ml, Ethambutol - 2.5 µg/ml, Ethionamide - 1.25 µg/ml, and Streptomycin - 2 µg/ml. The tests were evaluated using the indirect method in the BACTEC 460 TB (Becton Dickinson) system as the gold standard. The results showed that the Rifampin test performed best, i.e., 100% sensitivity at 95% Confidence Interval (82.2-100) and 100% specificity at 95% Confidence Interval (84.5-100), followed by Isoniazid and Pyrazinamide. In this experiment, 92% of the materials showed a final reading in 30 days; this period represents the time for primary isolation as well as the results of the sensitivity profile, and is within Centers for Disease Control and Prevention recommendations regarding time for performance of the antibiogram. The inoculated flasks showed no contamination during the experiment. The MB/BacT is shown to be a reliable, rapid, fully automated nonradiometric system for the tuberculosis antibiogram.

Acute Damage to the Posterior Limb of the Internal Capsule on Diffusion Tensor Tractography as an Early Imaging Predictor of Motor Outcome after Stroke

Background and Purpose Early prediction of motor outcome is of interest in stroke management. We aimed to determine whether lesion location at DTT is predictive of motor outcome after acute stroke and whether this information improves the predictive accuracy of the clinical scores. Methods We evaluated 60 consecutive patients within 12 hours of MCA stroke onset. We used DTT to evaluate CST involvement in the MC and PMC, CS, CR, and PLIC and in combinations of these regions at admission, at day 3, and at day 30. Severity of limb weakness was assessed using the m-NIHSS (5a, 5b, 6a, 6b). We calculated volumes of infarct and FA values in the CST of the pons. Results Acute damage to the PLIC was the best predictor associated with poor motor outcome, axonal damage, and clinical severity at admission (P&.001). There was no significant correlation between acute infarct volume and motor outcome at day 90 (P=.176, r=0.485). The sensitivity, specificity, and positive and negative predictive values of acute CST involvement at the level of the PLIC for 4 motor outcome at day 90 were 73.7%, 100%, 100%, and 89.1%, respectively. In the acute stage, DTT predicted motor outcome at day 90 better than the clinical scores (R2=75.50, F=80.09, P&.001). Conclusions In the acute setting, DTT is promising for stroke mapping to predict motor outcome. Acute CST damage at the level of the PLIC is a significant predictor of unfavorable motor outcome.

Immunogenicity test of tetanus component in adsorbed vaccines by toxin binding inhibition test

Samples from 20 lots of diphtheria-tetanus (adult use dT) vaccine and from 20 lots of diphtheria-tetanus-pertussis (DTP) vaccine were used to standardize and validate the in vitro toxin binding inhibition (ToBI) test for the immunogenicity test of the tetanus component. The levels of tetanus antitoxin obtained by ToBI test were compared to those obtained using the toxin neutralization (TN) test in mice routinely employed to perform the quality control of the tetanus component in adsorbed vaccines. The results ranged from 1.8 to 3.5 IU/ml for dT and 2 to 4 IU/ml for DTP by ToBI test and 1.4 to 3 IU/ml for dT and 1.8 to 3.5 IU/ml for DTP by TN in mice. These results were significantly correlated. From this study, it is concluded that the ToBI test is an alternative to the in vivo neutralization procedure in the immunogenicity test of the tetanus component in adsorbed vaccines. A substantial refinement and a reduction in use of animals can be achieved.

Angiostrongylus costaricensis and experimental infection of Sarasinula marginata II: elimination routes

Angiostrongylus costaricensis intermediate hosts are terrestrial mollusks mostly belonging to the Veronicellidae family. In the present investigation we focused on the mechanisms of larval expulsion from Sarasinula marginata infected with A. costaricensis. Twenty-five mollusks were individually infected with 5000 L1 and sacrificed at 30 min and 1, 2, 4, 6, and 8 h post-infection and at days 1, 2, 4, 5, 6, 8, 10, 11, 12, 14, 15, 16, 20, 21, 22, 25, 26, 28, and 30 post-infection; the mollusks were then fixed and stained. Diverse organs involved throughout the course of the migratory routes of larvae from oral penetration on were specified and the mechanisms of larval access to the fibromuscular layer through the kidney, rectum, and vascular system were defined. The elimination of L3, derived from oral and/or cutaneous infections, appears to depend on granulomas located close to the excretory ducts of mucous cells.

Cervical screening programme: HPV triage and test of cure protocol

Testing for high-risk human papillomavirus (HR-HPV) as triage and test of cure was introduced into the Northern Ireland Cervical Screening Programme on Monday 28 January 2013. This policy change will significantly alter the screening pathway for women with a mild dyskaryosis or borderline smear result. The link between HR-HPV infection and the development of cervical cancer has now been clearly established, with almost 100% of cervical cancers containing HPV DNA. Women with no evidence of HR-HPV infection are extremely unlikely to develop cervical cancer in the short to medium term. HPV triage is the process whereby HR-HPV testing is used to manage women with low grade cervical abnormalities. Only 15-20% of women with a borderline or mild smear result have a significant abnormality that needs treatment. HR-HPV testing is effective in identifying which women may need treatment and allows colposcopy resources to be allocated more effectively.The test of cure process is being introduced because it is now known that women with a normal or low grade smear test, and who are HR-HPV negative at six months after treatment, are at very low risk of residual disease. These women do not need to be recalled for another screening appointment for three years.The test of cure process means all post-treatment smears (at six months) that are reported as normal, borderline or mild dyskaryosis will be tested for HR-HPV. Those women who are HR-HPV positive will remain at colposcopy. HR-HPV negative women can be safely returned to recall in three years. It is estimated that the HR-HPV test of cure will allow approximately 80% of women who have been through treatment to avoid undergoing annual smear tests. This flowchart poster outlines the new triage and test of cure process. It was distributed to all GPs in Northern Ireland and is available to download as a PDF from this website.�

"Royal" pediculosis in Renaissance Italy: lice in the mummy of the King of Naples Ferdinand II of Aragon (1467-1496)

Pediculosis seems to have afflicted humans since the most ancient times and lice have been found in several ancient human remains. Examination of the head hair and pubic hair of the artificial mummy of Ferdinand II of Aragon (1467-1496), King of Naples, revealed a double infestation with two different species of lice, Pediculus capitis, the head louse, and Pthirus pubis, the pubic louse. The hair samples were also positive for the presence of mercury, probably applied as an anti-pediculosis therapy. This is the first time that these parasites have been found in the hair of a king, demonstrating that even members of the wealthy classes in the Renaissance were subject to louse infestation.

Intrinsic test of independence in contingency tables

A condition needed for testing nested hypotheses from a Bayesianviewpoint is that the prior for the alternative model concentratesmass around the small, or null, model. For testing independencein contingency tables, the intrinsic priors satisfy this requirement.Further, the degree of concentration of the priors is controlled bya discrete parameter m, the training sample size, which plays animportant role in the resulting answer regardless of the samplesize.In this paper we study robustness of the tests of independencein contingency tables with respect to the intrinsic priors withdifferent degree of concentration around the null, and comparewith other “robust” results by Good and Crook. Consistency ofthe intrinsic Bayesian tests is established.We also discuss conditioning issues and sampling schemes,and argue that conditioning should be on either one margin orthe table total, but not on both margins.Examples using real are simulated data are given

Motor overactivity and loss of motor circadian rhythm in fatal familial insomnia: an actigraphic study.

The 24-hour rest-activity pattern and the amount of motor activity was studied in a patient with fatal familial insomnia (FFI) by means of wrist actigraphy. During the study, the patient underwent indirect calorimetry. The 52-day recording showed severe disruption of the 24-hour rest-activity pattern with increased motor activity up to 80%. The 24-hour energy expenditure, assayed in a respiration chamber, was strikingly elevated by 60%. Chronic motor overactivity and loss of circadian rest-activity rhythm may play a role in the progressive metabolic exhaustion leading to death in FFI patients.

Experimental benznidazole treatment of Trypanosoma cruzi II strains isolated from children of the Jequitinhonha Valley, Minas Gerais, Brazil, with Chagas disease

Trypanosoma cruzi strains from distinct geographic areas show differences in drug resistance and association between parasites genetic and treatment response has been observed. Considering that benznidazole (BZ) can reduce the parasite burden and tissues damage, even in not cured animals and individuals, the goal is to assess the drug response to BZ of T. cruzi II strains isolated from children of the Jequitinhonha Valley, state of Minas Gerais, Brazil, before treatment. Mice infected and treated with BZ in both phases of infection were compared with the untreated and evaluated by fresh blood examination, haemoculture, polymerase chain reaction, conventional (ELISA) and non-conventional (FC-ALTA) serologies. In mice treated in the acute phase, a significant decrease in parasitaemia was observed for all strains. Positive parasitological and/or serological tests in animals treated during the acute and chronic (95.1-100%) phases showed that most of the strains were BZ resistant. However, beneficial effect was demonstrated because significant reduction (p < 0.05%) and/or suppression of parasitaemia was observed in mice infected with all strains (acute phase), associated to reduction/elimination of inflammation and fibrosis for two/eight strains. BZ offered some benefit, even in not cured animals, what suggest that BZ use may be recommended at least for recent chronic infection of the studied region.