Modeling the risk of malaria for travelers to areas with stable malaria transmission

Background: Malaria is an important threat to travelers visiting endemic regions. The risk of acquiring malaria is complex and a number of factors including transmission intensity, duration of exposure, season of the year and use of chemoprophylaxis have to be taken into account estimating risk. Materials and methods: A mathematical model was developed to estimate the risk of non-immune individual acquiring falciparum malaria when traveling to the Amazon region of Brazil. The risk of malaria infection to travelers was calculated as a function of duration of exposure and season of arrival. Results: The results suggest significant variation of risk for non-immune travelers depending on arrival season, duration of the visit and transmission intensity. The calculated risk for visitors staying longer than 4 months during peak transmission was 0.5% per visit. Conclusions: Risk estimates based on mathematical modeling based on accurate data can be a valuable tool in assessing risk/benefits and cost/benefits when deciding on the value of interventions for travelers to malaria endemic regions.

Spatio-Temporal Tracking and Phylodynamics of an Urban Dengue 3 Outbreak in Sao Paulo, Brazil

The dengue virus has a single-stranded positive-sense RNA genome of similar to 10.700 nucleotides with a single open reading frame that encodes three structural (C, prM, and E) and seven nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins. It possesses four antigenically distinct serotypes (DENV 1-4). Many phylogenetic studies address particularities of the different serotypes using convenience samples that are not conducive to a spatio-temporal analysis in a single urban setting. We describe the pattern of spread of distinct lineages of DENV-3 circulating in Sao Jose do Rio Preto, Brazil, during 2006. Blood samples from patients presenting dengue-like symptoms were collected for DENV testing. We performed M-N-PCR using primers based on NS5 for virus detection and identification. The fragments were purified from PCR mixtures and sequenced. The positive dengue cases were geo-coded. To type the sequenced samples, 52 reference sequences were aligned. The dataset generated was used for iterative phylogenetic reconstruction with the maximum likelihood criterion. The best demographic model, the rate of growth, rate of evolutionary change, and Time to Most Recent Common Ancestor (TMRCA) were estimated. The basic reproductive rate during the epidemics was estimated. We obtained sequences from 82 patients among 174 blood samples. We were able to geo-code 46 sequences. The alignment generated a 399-nucleotide-long dataset with 134 taxa. The phylogenetic analysis indicated that all samples were of DENV-3 and related to strains circulating on the isle of Martinique in 2000-2001. Sixty DENV-3 from Sao Jose do Rio Preto formed a monophyletic group (lineage 1), closely related to the remaining 22 isolates (lineage 2). We assumed that these lineages appeared before 2006 in different occasions. By transforming the inferred exponential growth rates into the basic reproductive rate, we obtained values for lineage 1 of R(0) = 1.53 and values for lineage 2 of R(0) = 1.13. Under the exponential model, TMRCA of lineage 1 dated 1 year and lineage 2 dated 3.4 years before the last sampling. The possibility of inferring the spatio-temporal dynamics from genetic data has been generally little explored, and it may shed light on DENV circulation. The use of both geographic and temporally structured phylogenetic data provided a detailed view on the spread of at least two dengue viral strains in a populated urban area.

A Comparison of Bimatoprost 0.03% Versus the Fixed-Combination of Latanotoprost 0.005% and Timolol 0.5% in Adult Patients With Elevated Intraocular Pressure: An Eight-Week, Randomized, Open-Label Trial

Introduction and Purpose: Bimatoprost and the fixed combination of latanoprost with timolol maleate are 2 medications widely used to treat glaucoma and ocular hypertension (OHT). The aim of the study is to compare the efficacy of these 2 drugs in reducing intraocular pressure (IOP) after 8 weeks of treatment in patients with primary open angle glaucoma (POAG) or OHT. Methods: In this randomized, open-label trial, 44 patients with POAG or OHT were allocated to receive either bimatoprost (1 drop QD) or latanoprost/timolol (1 drop QD). Primary outcome was the mean diurnal IOP measurement at the 8th week, calculated as the mean IOP measurements taken at 8:00 AM, 10: 00 AM, and 12: 00 PM Secondary outcomes included the baseline change in IOP measured 3 times a day, after the water-drinking test (performed after the last IOP measurement), and the assessment of side effects of each therapy. Results: The mean IOP levels of latanoprost/timolol (13.83, SD = 2.54) was significantly lower than of bimatoprost (16.16, SD = 3.28; P < 0.0001) at week 8. Also, the change in mean IOP values was significantly higher in the latanoprost/timolol group at 10:00 AM (P = 0.013) and 12:00 PM (P = 0.01), but not at 8: 00 AM (P = ns). During the water-drinking test, there was no signifi cant difference in IOP increase (absolute and percentage) between groups; however, there was a signifi cant decrease in mean heart rate in the latanoprost/timolol group. Finally, no signifi cant changes in blood pressure and lung spirometry were observed in either groups. Conclusions: The fixed combination of latanoprost/timolol was significantly superior to bimatoprost alone in reducing IOP in patients with POAG or OHT. Further studies with large sample sizes should be taken to support the superior efficacy of latanoprost/timolol, as well as to better assess its profile of side effects.

Transmission potential, skin inflammatory response, and parasitism of symptomatic and asymptomatic dogs with visceral leishmaniasis

Background: Visceral leishmaniasis in Brazil is caused by the protozoan Leishmania (Leishmania) chagasi and it is transmitted by sandfly of the genus Lutzomyia. Dogs are an important domestic reservoir, and control of the transmission of visceral leishmaniasis (VL) to humans includes the elimination of infected dogs. However, though dogs are considered to be an important element in the transmission cycle of Leishmania, the identification of infected dogs representing an immediate risk for transmission has not been properly evaluated. Since it is not possible to treat infected dogs, they are sacrificed when a diagnosis of VL is established, a measure that is difficult to accomplish in highly endemic areas. In such areas, parameters that allow for easy identification of reservoirs that represents an immediate risk for transmission is of great importance for the control of VL transmission. In this study we aimed to identify clinical parameters, reinforced by pathological parameters that characterize dogs with potential to transmit the parasite to the vector. Results: The major clinical manifestations of visceral leishmaniasis in dogs from an endemic area were onicogriphosis, skin lesions, conjunctivitis, lymphadenopathy, and weight loss. The transmission potential of these dogs was assessed by xenodiagnosis using Lutzomyia longipalpis. Six of nine symptomatic dogs were infective to Lutzomyia longipalpis while none of the five asymptomatic dogs were infective to the sandfly. Leishmania amastigotes were present in the skin of all clinically symptomatic dogs, but absent in asymptomatic dogs. Higher parasite loads were observed in the ear and ungueal region, and lower in abdomen. The inflammatory infiltrate was more intense in the ears and ungueal regions of both symptomatic and asymptomatic dogs. In clinically affected dogs in which few or none Leishmania amastigotes were observed, the inflammatory infiltrate was constituted mainly of lymphocytes and macrophages. When many parasites were present, the infiltrate was also comprised of lymphocytes and macrophages, as well as a larger quantity of polymorphonuclear neutrophils (PMNs). Conclusion: Dogs that represent an immediate risk for transmission of Leishmania in endemic areas present clinical manifestations that include onicogriphosis, skin lesions, conjunctivitis, lymphadenopathy, and weight loss. Lymphadenopathy in particular was a positive clinical hallmark since it was closely related to the positive xenodiagnosis.

Prospective and Randomized Comparison of Two Techniques of Staple Line Reinforcement During Open Roux-en-Y Gastric Bypass: Oversewing and Bioabsorbable Seamguard (R)

Aims: Surgical staple line dehiscence usually leads to severe complications. Several techniques and materials have been used to reinforce this stapling and thus reduce the related complications. The objective was to compare safety of two types of anastomotic reinforcement in open gastric bypass. Methods: A prospective, randomized study comparing an extraluminal suture, fibrin glue, and a nonpermanent buttressing material, Seamguard (R), for staple line reinforcement. Fibrin glue was excluded from the study and analysis after two leaks, requiring surgical reintervention, antibiotic therapy, and prolonged patient hospitalization. Results: Twenty patients were assigned to the suture and Seamguard reinforcement groups. The groups were similar in terms of preoperative characteristics. No staple line dehiscence occurred in the two groups, whereas two cases of dehiscence occurred in the fibrin glue group. No mortality occurred and surgical time was statistically similar for both techniques. Seamguard made the surgery more expensive. Conclusion: In our service, staple line reinforcement in open bariatric surgery with oversewing or Seamguard was considered to be safe. Seamguard application was considered to be easier than oversewing, but more expensive.

Evaluating Patellar Kinematics Through Magnetic Resonance Imaging During Open- and Closed-Kinetic-Chain Exercises

Purpose: To evaluate patellar kinematics of volunteers Without knee pain at rest and during isometric contraction in open- and closed-kinetic-chain exercises. Methods: Twenty individuals took part in this study. All were submitted to magnetic resonance imaging (MRI) during rest and voluntary isometric contraction (VIC) in the open anti closed kinetic chain at 15 degrees, 30 degrees, and 45 degrees of knee flexion. Through MRI and using medical e-film software, the following measurements were evaluated: sulcus angle, patellar-tilt angle, and bisect offset. The mixed-effects linear model was used for comparison between knee positions, between rest and isometric contractions, and between (he exercises. Results: Data analysis revealed that the sulcus angle decreased as knee flexion increased and revealed increases with isometric contractions in both the open and closed kinetic chain for all knee-flexion angles. The patellar-tilt angle decreased with isometric contractions in both the open and closed kinetic chain for every knee position. However, in the closed kinetic chain, patellar tilt increased significantly with the knee flexed at 15 degrees. The bisect offset increased with the knee flexed at 15 degrees during isometric contractions and decreased as knee flexion increased during both exercises. Conclusion: VIC in the last degrees of knee extension may compromise patellar dynamics. On the other hand, it is possible to favor patellar stability by performing muscle contractions with the knee flexed at 30 degrees and 45 degrees in either the open or closed kinetic chain.

Acute reversible inactivation of the bed nucleus of stria terminalis induces antidepressant-like effect in the rat forced swimming test

Background: The bed nucleus of stria terminalis (BNST) is a limbic forebrain structure involved in hypothalamo-pituitary-adrenal axis regulation and stress adaptation. Inappropriate adaptation to stress is thought to compromise the organism's coping mechanisms, which have been implicated in the neurobiology of depression. However, the studies aimed at investigating BNST involvement in depression pathophysiology have yielded contradictory results. Therefore, the objective of the present study was to investigate the effects of temporary acute inactivation of synaptic transmission in the BNST by local microinjection of cobalt chloride (CoCl(2)) in rats subjected to the forced swimming test (FST). Methods: Rats implanted with cannulae aimed at the BNST were submitted to 15 min of forced swimming (pretest). Twenty- four hours later immobility time was registered in a new 5 min forced swimming session (test). Independent groups of rats received bilateral microinjections of CoCl(2) (1 mM/100 nL) before or immediately after pretest or before the test session. Additional groups received the same treatment and were submitted to the open field test to control for unspecific effects on locomotor behavior. Results: CoCl(2) injection into the BNST before either the pretest or test sessions reduced immobility in the FST, suggesting an antidepressant-like effect. No significant effect of CoCl(2) was observed when it was injected into the BNST immediately after pretest. In addition, no effect of BNST inactivation was observed in the open field test. Conclusion: These results suggest that acute reversible inactivation of synaptic transmission in the BNST facilitates adaptation to stress and induces antidepressant-like effects.

Vectorial Competence of Larvae and Adults of Alphitobius diaperinus in the Transmission of Salmonella Enteritidis in Poultry

Introduction: The ingestion of food products originating from poultry infected with Salmonella spp. is one of the major causes of food poisoning in humans. The control of poultry salmonellosis is particularly difficult since birds are asymptomatic and numerous factors may expedite the maintenance of bacteria in poultry production facilities. Objective: The aim of the study was to determine the vectorial capacity of adults and larvae of Alphitobius diaperinus (Coleoptera: Tenebrionidae) in the experimental transmission of Salmonella Enteritidis phage type 4 to 1-day-old specific pathogen-free White Leghorn chicks. Methods: Adult insects and larvae were starved for 1 day, fed for 24 h or 7 days on sterile ration that had been treated with Salmonella Enteritidis phage type 4, and the levels of bacterial infection were determined. Infected adult insects and larvae were fed to groups of day-old chicks, after which bacteria were recovered from cecum, liver, and spleen samples over a 7-day period. Results: Infected larvae were more efficient than adult insects in transmitting Salmonella Enteritidis to chicks. Higher concentrations of bacteria could be reisolated from the cecum, liver, and spleen of chicks that had ingested infected larvae compared with those that had ingested infected adults. Conclusions: The control of A. diaperinus, and particularly of the larvae, represents a critical factor in the reduction of Salmonella spp. in poultry farms.

Alstonine as an Antipsychotic: Effects on Brain Amines and Metabolic Changes

Managing schizophrenia has never been a trivial matter. Furthermore, while classical antipsychotics induce extrapyramidal side effects and hyperprolactinaemia, atypical antipsychotics lead to diabetes, hyperlipidaemia, and weight gain. Moreover, even with newer drugs, a sizable proportion of patients do not show significant improvement. Alstonine is an indole alkaloid identified as the major component of a plant-based remedy used in Nigeria to treat the mentally ill. Alstonine presents a clear antipsychotic profile in rodents, apparently with differential effects in distinct dopaminergic pathways. The aim of this study was to complement the antipsychotic profile of alstonine, verifying its effects on brain amines in mouse frontal cortex and striatum. Additionally, we examined if alstonine induces some hormonal and metabolic changes common to antipsychotics. HPLC data reveal that alstonine increases serotonergic transmission and increases intraneuronal dopamine catabolism. In relation to possible side effects, preliminary data suggest that alstonine does not affect prolactin levels, does not induce gains in body weight, but prevents the expected fasting-induced decrease in glucose levels. Overall, this study reinforces the proposal that alstonine is a potential innovative antipsychotic, and that a comprehensive understanding of its neurochemical basis may open new avenues to developing newer antipsychotic medications.

Experimental Infection of the Opossum Didelphis aurita by Rickettsia felis, Rickettsia bellii, and Rickettsia parkeri and Evaluation of the Transmission of the Infection to Ticks Amblyomma cajennense and Amblyomma dubitatum

This work evaluated the infection of opossums (Didelphis aurita) by Rickettsia felis, Rickettsia bellii, and Rickettsia parkeri and their role as amplifier hosts for horizontal transmission to Amblyomma cajennense and/or Amblyomma dubitatum ticks. Infection in D. aurita was induced by intraperitoneal inoculation with R. felis (n = 4 opossums), R. bellii (n = 4), and R. parkeri (n = 2). Another group of six opossums were inoculated intraperitoneally with Leibovitz-15 sterile culture medium, representing the uninfected groups (n = 2 opossums simultaneously to each infected group). Opossum blood samples collected during the study were used for DNA extraction, followed by real-time polymerase chain reaction targeting the rickettsial gene gltA, hematology, and detection of Rickettsia spp.-reactive antibodies by indirect immunofluorescence assay. Opossums were infested with uninfected A. cajennense and/or A. dubitatum for 30 days postinoculation (DPI). Flat ticks molted from ticks fed on opossums were allowed to feed on uninfected rabbits, which were tested for seroconversion by immunofluorescence assay. Samples of flat ticks were also tested by real-time polymerase chain reaction. Inoculated opossums showed no clinical abnormalities. Antibodies to Rickettsia spp. were first detected at the second to fourth DPI, with detectable titers until the 150th DPI. Rickettsemia was detected only in one opossum inoculated with R. parkeri, at the eighth DPI. Only one A. cajennense tick (2.0%) previously fed on a R. parkeri-inoculated opossum became infected. None of the rabbits infested with opossum-derived ticks seroconverted. The study demonstrated that R. felis, R. bellii, and R. parkeri were capable to produce antibody response in opossums, however, with undetectable rickettsemia for R. felis and R. bellii, and very low rickettsemia for R. parkeri. Further studies must be done with different strains of these rickettsiae, most importantly the strains that have never gone through in vitro passages.

Experimental Infection of Opossums Didelphis aurita by Rickettsia rickettsii and Evaluation of the Transmission of the Infection to Ticks Amblyomma cajennense

The present study evaluated the infection of opossums (Didelphis aurita) by Rickettsia rickettsii and their role as amplifier hosts for horizontal transmission of R. rickettsii to Amblyomma cajennense ticks. Three groups of opossums were evaluated: on day 0, group 1 (G1) was inoculated intraperitoneally with R. rickettsii; group 2 (G2) was infested by R. rickettsii-infected ticks; and group 3 (G3) was the uninfected control group. Opossum rectal temperature was measured daily. Blood samples were collected every 2 to 4 days during 30 days, and used to (1) inoculate guinea pigs intraperitoneally; (2) extract DNA followed by real-time polymerase chain reaction (PCR) targeting the rickettsial gene gltA; (3) study hematology; (4) detect R. rickettsii-reactive antibodies by indirect direct immunofluorescence assay (IFA). Blood was also collected every 10 days from days 30 to 180, to be tested by serology. Opossums were infested by uninfected A. cajennense larvae and nymphs from days 3 to 15. Engorged ticks were collected and allowed to molt in an incubator. Thereafter, the subsequent flat ticks were allowed to feed on uninfected rabbits, which were tested for seroconversion by IFA. Samples of flat ticks were also tested by real-time PCR. All G1 and G2 opossums became infected by R. rickettsii, as demonstrated by real-time PCR or/and guinea pig inoculation, but they showed no clinical abnormality. Rickettsemia was first detected at days 2 to 8, lasting intermittently till days 1 to 30. Approximately 18% and 5% of the flat ticks previously fed on G1 and G2 opossums, respectively, became infected by R. rickettsii, but only the rabbits infested with G1-derived ticks seroconverted. The study demonstrated that R. rickettsii was capable of infecting opossums without causing illness and developing rickettsemia capable of causing infection in guinea pigs and ticks, although the infection rate in ticks was low.

Transmission electron microscopy for characterization of acrosomal damage after Percoll gradient centrifugation of cryopreserved bovine spermatozoa

The objective of this study was to characterize acrosomal ultrastructure following discontinuous Percoll gradient centrifugation of cryopreserved bovine sperm. Semen was collected from six bulls of different breeds and three ejaculates per bull were evaluated. Frozen semen samples were thawed and the acrosomal region of sperm cells was evaluated by transmission electron microscopy (TEM) before (n = 18) and after (n = 18) Percoll centrifugation. The evaluation of 20 sperm heads from each of the 36 samples analyzed ensured that a large number of cells were investigated. The data were subjected to analysis of variance at a level of significance of 5%. Percoll centrifugation reduced the percentage of sperm exhibiting normal acrosomes (from 61.77 to 30.24%), reduced the percentage of sperm presenting atypical acrosome reactions (from 28.38 to 4.84%) and increased the percentage of sperm exhibiting damage in the acrosome (from 6.14 to 64.26%). The percentage of sperm with typical acrosome reactions was not significantly different before (3.70%) and after (0.67%) centrifugation. TEM distinguished four different types of acrosomal status and enabled ultrastructural characterization of acrosomal injuries. The percentage of sperm exhibiting normal acrosomes decreased and damage in the acrosome was the most frequent acrosomal injury with the Percoll gradient centrifugation protocol utilized.

Kinematic parameters and membership probabilities of open clusters in the Bordeaux PM2000 catalogue

Aims. We derive lists of proper-motions and kinematic membership probabilities for 49 open clusters and possible open clusters in the zone of the Bordeaux PM2000 proper motion catalogue (+ 11 degrees <= delta <= + 18 degrees). We test different parametrisations of the proper motion and position distribution functions and select the most successful one. In the light of those results, we analyse some objects individually. Methods. We differenciate between cluster and field member stars, and assign membership probabilities, by applying a new and fully automated method based on both parametrisations of the proper motion and position distribution functions, and genetic algorithm optimization heuristics associated with a derivative-based hill climbing algorithm for the likelihood optimization. Results. We present a catalogue comprising kinematic parameters and associated membership probability lists for 49 open clusters and possible open clusters in the Bordeaux PM2000 catalogue region. We note that this is the first determination of proper motions for five open clusters. We confirm the non-existence of two kinematic populations in the region of 15 previously suspected non-existent objects.

A VLT/FLAMES survey for massive binaries in Westerlund 1 III. The WC9d binary W239 and implications for massive stellar evolution

Context. There is growing evidence that a treatment of binarity amongst OB stars is essential for a full theory of stellar evolution. However the binary properties of massive stars - frequency, mass ratio & orbital separation - are still poorly constrained. Aims. In order to address this shortcoming we have undertaken a multiepoch spectroscopic study of the stellar population of the young massive cluster Westerlund 1. In this paper we present an investigation into the nature of the dusty Wolf-Rayet star and candidate binary W239. Methods. To accomplish this we have utilised our spectroscopic data in conjunction with multi-year optical and near-IR photometric observations in order to search for binary signatures. Comparison of these data to synthetic non-LTE model atmosphere spectra were used to derive the fundamental properties of the WC9 primary. Results. We found W239 to have an orbital period of only similar to 5.05 days, making it one of the most compact WC binaries yet identified. Analysis of the long term near-IR lightcurve reveals a significant flare between 2004-6. We interpret this as evidence for a third massive stellar component in the system in a long period (> 6 yr), eccentric orbit, with dust production occuring at periastron leading to the flare. The presence of a near-IR excess characteristic of hot (similar to 1300 K) dust at every epoch is consistent with the expectation that the subset of persistent dust forming WC stars are short (< 1 yr) period binaries, although confirmation will require further observations. Non-LTE model atmosphere analysis of the spectrum reveals the physical properties of the WC9 component to be fully consistent with other Galactic examples. Conclusions. The simultaneous presence of both short period Wolf-Rayet binaries and cool hypergiants within Wd 1 provides compelling evidence for a bifurcation in the post-Main Sequence evolution of massive stars due to binarity. Short period O+OB binaries will evolve directly to the Wolf-Rayet phase, either due to an episode of binary mediated mass loss - likely via case A mass transfer or a contact configuration - or via chemically homogenous evolution. Conversely, long period binaries and single stars will instead undergo a red loop across the HR diagram via a cool hypergiant phase. Future analysis of the full spectroscopic dataset for Wd 1 will constrain the proportion of massive stars experiencing each pathway; hence quantifying the importance of binarity in massive stellar evolution up to and beyond supernova and the resultant production of relativistic remnants.

Beryllium abundances along the evolutionary sequence of the open cluster IC 4651-A new test for hydrodynamical stellar models

Context. Previous analyses of lithium abundances in main sequence and red giant stars have revealed the action of mixing mechanisms other than convection in stellar interiors. Beryllium abundances in stars with Li abundance determinations can offer valuable complementary information on the nature of these mechanisms. Aims. Our aim is to derive Be abundances along the whole evolutionary sequence of an open cluster. We focus on the well-studied open cluster IC 4651. These Be abundances are used with previously determined Li abundances, in the same sample stars, to investigate the mixing mechanisms in a range of stellar masses and evolutionary stages. Methods. Atmospheric parameters were adopted from a previous abundance analysis by the same authors. New Be abundances have been determined from high-resolution, high signal-to-noise UVES spectra using spectrum synthesis and model atmospheres. The careful synthetic modeling of the Be lines region is used to calculate reliable abundances in rapidly rotating stars. The observed behavior of Be and Li is compared to theoretical predictions from stellar models including rotation-induced mixing, internal gravity waves, atomic diffusion, and thermohaline mixing. Results. Beryllium is detected in all the main sequence and turn-off sample stars, both slow- and fast-rotating stars, including the Li-dip stars, but is not detected in the red giants. Confirming previous results, we find that the Li dip is also a Be dip, although the depletion of Be is more modest than for Li in the corresponding effective temperature range. For post-main-sequence stars, the Be dilution starts earlier within the Hertzsprung gap than expected from classical predictions, as does the Li dilution. A clear dispersion in the Be abundances is also observed. Theoretical stellar models including the hydrodynamical transport processes mentioned above are able to reproduce all the observed features well. These results show a good theoretical understanding of the Li and Be behavior along the color-magnitude diagram of this intermediate-age cluster for stars more massive than 1.2 M(circle dot).