Acceptability, feasibility and cost of point of care testing for sexually transmitted infections among South African adolescents where syndromic management is standard of care.

BACKGROUND: Young people (YP) in southern Africa are at substantial risk of HIV and sexually transmitted infections (STIs). Despite the epidemiological and biological link between STIs and HIV transmission and acquisition, infections such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) remain widely undiagnosed. Syndromic STI management is the standard of care in low- and middle-income countries (LMICs) despite a high prevalence of asymptomatic infections. We conducted an observational study to explore the acceptability, feasibility, and cost of a STI test-and-treat service for YP in Cape Town. METHODS: YP attending a mobile clinic (MC) and a youth centre clinic (YC) were offered STI screening. Urine testing for CT and NG using a 90-min molecular point-of-care (POC) test on the GeneXpert platform was conducted and treatment provided. Data were collated on demographics, sexual behaviour, presence of symptoms, uptake of same-day treatment, prevalence of CT/NG, and service acceptability. RESULTS: Three hundred sixty six participants were enrolled (median age 20, 83% female).57% (209/366) of participants tested positive for either CT (126/366, 34%) or NG (57/366, 16%) or co-infection (26/366, 7%). Clinical symptoms were a poor predictor of GeneXpert diagnosed CT or NG, with a sensitivity of 46.8% and 54.0% for CT and NG respectively. Although half of participants initially chose to receive same day results and treatment, only a third waited for results on the day. The majority of participants (91%) rated the service highly via a post-visit acceptability questionnaire. CONCLUSION: Curable STIs are highly prevalent in this population. STI screening using POC testing was feasible and acceptability was high. The study provides further impetus for moving policy beyond syndromic management of STIs in South Africa.

Design and expression of polytopic construct of cathepsin-L1, SAP-2 and FhTP16.5 proteins of Fasciola hepatica.

The enzyme-linked immunosorbent assay (ELISA) technique can play an important role in the early detection of fascioliasis. However, they have some diagnostic limitations, including cross-reaction with other helminths. It seems that the combination of recombinant parasite proteins as antigen can reduce these problems. Hence, the present study was aimed to design and confirm the antigenic recombinant multi-epitope (rMEP) construct of three protein epitopes (linear and conformational B-cell epitopes) of the parasite using immunoinformatic tools. For this purpose, the tertiary structures of Fasciola hepatica cathepsin-L1, saposin-like protein 2 and 16.5-kDa tegument-associated protein were predicted using the I-TASSER server. Validation of the modelled structures was performed by Ramachandran plots. The antigenic epitopes of the proteins were achieved by analysing the features of the IEDB server. The synthesized gene was cloned into the pET-22b (+) expression vector and transformed into the Escherichia coli BL21. Sodium dodecyl sulfate polyacrylamide gel electrophoresis was used to verify and analyse the expression of the rMEP protein. Western blotting was utilized to confirm rMEP protein immunogenicity in two forms, one using an anti-His tag antibody and the other with human pooled sera samples (fascioliasis, non-fascioliasis and negative control sera). Our results demonstrated that the rMEP designed for the three proteins of F. hepatica was highly antigenic, and immune-detection techniques confirmed the antigen specificity. In conclusion, the presented antigenic multi-epitope may be very helpful to develop serodiagnostic kits such as indirect ELISA to evaluate the proper diagnosis of fascioliasis in humans and ruminants.

Effective, appropriate and simple culture, egg hatching and cryopreserving of the nematode Cheilospirura hamulosa.

1. Successful invasion by nematode parasites is associated with several factors including egg hatching at the right time in their hosts. To determine a simple and appropriate medium for culture and egg hatching of the highly pathogenic species of the Acuariidae family, Cheilospirura hamulosa were cultured in three different media. In addition the viability of C. hamulosa eggs was determined after storage in frozen infected gizzards. 2. Eggs removed from the uteri of the female worms in infected gizzards were pooled and washed in distilled water and screened under a stereo dissecting microscope. Eggs were counted and cultured in three different media, nutrient agar, normal saline 0.9% and Bearman, at room temperature. Additionally, 10 infected gizzards were kept at -20°C for 2 and 8 months. 3. After 4-5 d there had been no growth in the nutrient agar medium, whereas 11% of the cultured eggs in the Bearman medium contained larvae 2-3 d after culturing. In 0.9% normal saline medium the two polar knobs appeared on the two poles of the eggs at 2 d post cultivation, and 74% of the eggs contained a larva on the third day. Mature larvae gradually exited from the eggs. 4. Eggs collected from female worms in gizzards frozen at -20°C were cultured in the same three culture media at room temperature. Larvae were visible in the eggs after 2-3 d in the Bearman and 0.9% normal saline media and hatched thereafter. 5. The 0.9% normal saline medium is recommended for egg hatching and cultivation of C. hamulosa due for simplicity, efficacy and cost effectiveness. Moreover, freezing of the infected gizzards at -20°C is proposed for long-term storage of the eggs.

Watersheds are Schramm-Loewner evolution curves.

We show that in the continuum limit watersheds dividing drainage basins are Schramm-Loewner evolution (SLE) curves, being described by one single parameter κ. Several numerical evaluations are applied to ascertain this. All calculations are consistent with SLE(κ), with κ = 1.734 ± 0.005, being the only known physical example of an SLE with κ<2. This lies outside the well-known duality conjecture, bringing up new questions regarding the existence and reversibility of dual models. Furthermore, it constitutes a strong indication for conformal invariance in random landscapes and suggests that watersheds likely correspond to a logarithmic conformal field theory with a central charge c ≈ -7/2.

Isolation and detection of Leishmania species among naturally infected Rhombomis opimus, a reservoir host of zoonotic cutaneous leishmaniasis in Turkemen Sahara, North East of Iran.

In Iran, three species of Leishmania have been incriminated as the causative agents of human leishmaniasis, Leishmania (L.) major, Leishmania tropica, and Leishmania infantum.Rhombomis opimus have been incriminated as a principal reservoirs of the parasitic protozoan Leishmania major, the causative agent of rural zoonotic cutaneous leishmaniasis (ZCL) in Iran. Rodents captured and examined to find Leishmania species using conventional methods including direct impression smear and microscopic observation inoculation samples to Balb/c and culture in NNN medium. Also molecular method was employed to detect Leishmania in rodents by amplifying a region of the ribosomal RNA amplicon of Leishmania (ITS1-5.8S rRNA-ITS2) using Nested PCR. Leshmania species were specified by DNA sequences. 36 (38.3%) of R. opimus were Leishmania positive using at least one conventional methods. Many more ITS-rDNA fragments were amplified from R. opimus but only 65 out of 74 PCR products contained enough DNA for direct sequencing or readable sequences. The PCR assays detected in Iranian R. opimus not only Leishmania major in 59 (79.7%) rodents but also Leishmania turanica in 6 (8.1%) rodents, another parasite of the great gerbil. These parasites were found in Turkemen Sahara, North East of Iran, in a focus of rural (ZCL). L. major and L. turanica in R. opimus firmly identified from Turkemen Sahara. Nine rodents with Leishmania infections unidentified which some were unreadable sequences, these could be mixed infections of L. major, L. turanica, Leishmania gerbillisensu lato and Leishmania close to L. gerbilli or a related species reported in sandflies previously from this location. The haplotypes of L. major and L. turanica were found to be identical to that of isolates of L. major and L. turanica from Iran and in GenBank elsewhere. R. opimus is probably the key reservoir in this ZCL focus because of its abundance and its infection rates with both L. major and L. turanica.

Scaling of clusters and winding-angle statistics of isoheight lines in two-dimensional Kardar-Parisi-Zhang surfaces.

We investigate the statistics of isoheight lines of (2+1) -dimensional Kardar-Parisi-Zhang model at different level sets around the mean height in the saturation regime. We find that the exponent describing the distribution of the height-cluster size behaves differently for level cuts above and below the mean height, while the fractal dimensions of the height-clusters and their perimeters remain unchanged. The statistics of the winding angle confirms the previous observation that these contour lines are in the same universality class as self-avoiding random walks.

Direct evidence for conformal invariance of avalanche frontiers in sandpile models.

Appreciation of stochastic Loewner evolution (SLE_{kappa}) , as a powerful tool to check for conformal invariant properties of geometrical features of critical systems has been rising. In this paper we use this method to check conformal invariance in sandpile models. Avalanche frontiers in Abelian sandpile model are numerically shown to be conformally invariant and can be described by SLE with diffusivity kappa=2 . This value is the same as value obtained for loop-erased random walks. The fractal dimension and Schramm's formula for left passage probability also suggest the same result. We also check the same properties for Zhang's sandpile model.

Conformal invariance of isoheight lines in a two-dimensional Kardar-Parisi-Zhang surface.

The statistics of isoheight lines in the (2+1) -dimensional Kardar-Parisi-Zhang (KPZ) model is shown to be conformally invariant and equivalent to those of self-avoiding random walks. This leads to a rich variety of exact analytical results for the KPZ dynamics. We present direct evidence that the isoheight lines can be described by the family of conformally invariant curves called Schramm-Loewner evolution (or SLE_{kappa} ) with diffusivity kappa=8/3 . It is shown that the absence of the nonlinear term in the KPZ equation will change the diffusivity kappa from 8/3 to 4, indicating that the isoheight lines of the Edwards-Wilkinson surface are also conformally invariant and belong to the universality class of domain walls in the O(2) spin model.

Crystal structure of the D85S mutant of bacteriorhodopsin: model of an O-like photocycle intermediate.

Crystal structures are reported for the D85S and D85S/F219L mutants of the light-driven proton/hydroxyl-pump bacteriorhodopsin. These mutants crystallize in the orthorhombic C222(1) spacegroup, and provide the first demonstration that monoolein-based cubic lipid phase crystallization can support the growth of well-diffracting crystals in non-hexagonal spacegroups. Both structures exhibit similar and substantial differences relative to wild-type bacteriorhodopsin, suggesting that they represent inherent features resulting from neutralization of the Schiff base counterion Asp85. We argue that these structures provide a model for the last photocycle intermediate (O) of bacteriorhodopsin, in which Asp85 is protonated, the proton release group is deprotonated, and the retinal has reisomerized to all-trans. Unlike for the M and N photointermediates, where structural changes occur mainly on the cytoplasmic side, here the large-scale changes are confined to the extracellular side. As in the M intermediate, the side-chain of Arg82 is in a downward configuration, and in addition, a pi-cloud hydrogen bond forms between Trp189 NE1 and Trp138. On the cytoplasmic side, there is increased hydration near the surface, suggesting how Asp96 might communicate with the bulk during the rise of the O intermediate.

Stability of brain content of magnesium in experimental hypomagnesemia.

Magnesium is important in cerebral function. If there is a deficiency and neurological symptoms accrue, we hypothesised that Mg2+ deficiency causes neurological symptoms by decreasing the level of Mg2+ in cerebral tissue. The content of magnesium was determined in 12 brain structures in magnesium-deficient rats. Experiments were carried out for 40 days in two groups of Wistar male rats made magnesium-deficient (MD) by a well-controlled diet (50 mg of Mg2+/kg of food), and a control group (CG) rats fed normal diet (1 g of Mg2+/kg of food). At the end of the 40 days, the clinical signs of hypomagnesemia were sought in the MD rats and Mg2+ concentration levels were measured in the blood and brain. The results showed variable distribution of Mg2+ in the different brain structures, both in CG and MD rats; in the MD rats there is an important stability of global Mg2+ content of the brain. Although the global values for Mg2+ in the brain did not decline in MD rats, there was a significant decrease in Mg2+ in the brainstem. We conclude that the brain is able to maintain a stable concentration of Mg2+ during chronic hypomagnesemia, but its topographic variations could account for some of neurological signs accompanying this condition.

Circadian variations in vigilance states in the alcohol-dependent rat.

Waking and sleep states were studied in the alcohol-dependent rat after administration of ethanol (416 mg/kg/hr) by indwelling intragastric catheter (IGC) for 13 days. Electropolygraphic recordings performed for a total of 24 hr from the start of withdrawal were compared with those of control rats receiving water by IGC and showed 1) that rapid eye movement sleep was the most sensitive of the four vigilance states studied. A decrease was noted both for the total duration of recording and for the light period; 2) that nonactive wakefulness was the only vigilance state to show an inversion of percentages between the light and dark period; 3) that the light period was the best time for studying changes in vigilance states. Changes included increased percentages of active and nonactive wakefulness and decreased percentages of slow-wave and rapid eye movement sleep. This was due to a change in the number of episodes rather to a change in their mean duration. No significant change occurred during the dark period.

Effects of alcohol dependence on shock-induced fighting: action of muscimol and homotaurine.

We have applied the electroshock-induced fighting behavior to the study of experimental alcohol dependence. Adult Wistar rats were intoxicated chronically with ethanol (10 g/kg/24 h) for 13 days. Electroshock-induced fighting behavior was studied during chronic intoxication and withdrawal in comparison with normal rats receiving a water-carbohydrate solution isocaloric to ethanol. Rats were divided into groups receiving respectively muscimol (0.25 mg/kg), a GABAA agonist; homotaurine (140 mg/kg) a GABA mimetic; and physiological saline (10 ml/kg), intraperitoneally. During chronic intoxication, rats showed an increase in defensive-fighting behavior. Withdrawal accentuated the aggressive behavior and muscimol and homotaurine inhibited it. These results confirm the relevance of the electroshock-induced defensive fighting behavior test in chronic intoxication with alcohol, but to show the involvement of GABAergic transmission in the behavioral effects of alcohol withdrawal, additional experiments with other GABA mimetics and with GABA antagonists should be considered.

Effects of muscimol or homotaurine on sleep-wake states in alcohol-dependent rats during withdrawal.

Sleep-wake states were studied following withdrawal in 36 adult male wistar alcohol-dependent rats, after chronic administration of ethanol (10 g/kg/24 h) for 13 days. In the light phase of the withdrawal day, 12 alcohol-dependent rats received muscimol (0.25 mg/kg), 12 received homotaurine (140 mg/kg), and 12 received 0.9% physiological saline (10 ml/kg). The results have been compared with a control group of 36 rats that received water during the treatment phase of the experiment, and the 14th day received intraperitoneal muscimol or homotaurine. Muscimol significantly improves the alterations of sleep-wake states in alcohol-withdrawn rats, decreasing the percentage of active wakefulness and increasing the percentage of REMS, but without any action on the latency of appearance of REMS, which remains shortened. The effects of homotaurine are less important on the wakefulness, but it also increases the percentage of REMS without influencing its latency of appearance. The influence of these GABA(A) agonists is not identical during the whole period of survey in the light phase, as there are important differences in the temporal sequences for each of them. We conclude that the stimulation of GABA(A) receptors, of which the activity is decreased during alcohol withdrawal, significantly improves the disturbances in the sleep-wake states in the alcohol-dependent rats, in a time-related manner, and there are significant pharmacodynamic differences between muscimol and homotaurine.

EEG effects of a single low dose of ethanol on afternoon sleep in the nonalcohol-dependent adult.

Three polygraphic recordings (PGR) of afternoon sleep (ANS) related to the duration of one sleep cycle, i.e., 90 min, were performed in 14 healthy adult volunteers (7 men and 7 women): two reference PGR, on two consecutive days (before ingestion of alcohol). Only the second being retained: reference PGR = P1; another recording, on day 3, 50 min after the start of single slow oral ingestion of the equivalent of 0.25 g 95% ethyl alcohol (ETOH) per kg body weight. Alcohol was ingested as 40 degrees whiskey, and the volume administered ranged from 34.5 to 66 ml (ETOH polygraphic recording = P2). Analysis of polygraphic traces was carried out according to the criteria of Rechtschaffen and Kales, and results were presented using the parameters adopted by Gross et al. (2). A single low dose of alcohol, leading to a low mean blood alcohol level (below 30 mg/100 ml, range 9 to 29 mg/100 ml), clearly perturbs sleep in the normal nonalcohol-dependent adult. In this context, ETOH does not appear to be a hypnotic since: a) the latencies to onset of sleep and the appearance of stages II, III, and IV of slow-wave sleep (SWS) are not shortened; b) the total duration of sleep, the percentage of delta sleep, and the duration (and percentage) of rapid eye movement sleep (REMS) are decreased; c) the number, duration, and percentages of intrasleep awakenings are increased, as are the number of stage changes. In addition, the study of afternoon sleep has shown itself to be a sensitive and reliable test for the analysis of the effects of a low dose of alcohol on nonalcohol-dependent subjects.

Cobalt(II)-selective membrane electrode based on a recently synthesized benzo-substituted macrocyclic diamide.

A PVC-membrane electrode based on a recently synthesized 18-membered macrocyclic diamide is presented. The electrode reveals a Nernstian potentiometric response for Co2+ over a wide concentration range (2.0 x 10(-6)-1.0 x 10(-2) M). The electrode has a response time of about 10 s and can be used for at least 2 months without any divergence. The proposed sensor revealed very good selectivities for Co2+ over a wide variety of other metal ions, and could be used over a wide pH range (3.0-8.0). The detection limit of the sensor is 6.0 x 10(-7) M. It was successfully applied to the direct determination and potentiometric titration of cobalt ion.

Loop-erased random walk on a percolation cluster: crossover from Euclidean to fractal geometry.

We study loop-erased random walk (LERW) on the percolation cluster, with occupation probability p ≥ p_{c}, in two and three dimensions. We find that the fractal dimensions of LERW_{p} are close to normal LERW in a Euclidean lattice, for all p>p_{c}. However, our results reveal that LERW on critical incipient percolation clusters is fractal with d_{f}=1.217 ± 0.002 for d=2 and 1.43 ± 0.02 for d=3, independent of the coordination number of the lattice. These values are consistent with the known values for optimal path exponents in strongly disordered media. We investigate how the behavior of the LERW_{p} crosses over from Euclidean to fractal geometry by gradually decreasing the value of the parameter p from 1 to p_{c}. For finite systems, two crossover exponents and a scaling relation can be derived. This work opens up a theoretical window regarding the diffusion process on fractal and random landscapes.

Molecular detection and conventional identification of leishmania species in reservoir hosts of zoonotic cutaneous leishmaniasis in fars province, South of iran.

BACKGROUND: The objectives of our research were to search for Leishmania species in rodents in Fars province, south of Iran, and to compare molecular with conventional methods for detecting these parasites. METHODS: Rodents were captured using live traps and screened for Leishmania species using molecular and conventional methods, including the taking of smears from each ear. Nested PCR was employed to detect Leishmania in rodents by amplifying a region of the ribosomal RNA amplicon of Leishmania (ITS1-5.8S rRNA-ITS2) that is species-specific by DNA sequence. RESULTS: Totally, 122 rodents were captured. Leishmania parasites were detected using the nested PCR and three conventional methods (direct smear, NNN culture and Balb/C inoculation. 41 (33.6%) out of 122 rodents had Leishmania infections (34 Meriones lybicus and 7 M. persicus). All PCR products of the ITS-rDNA gene were sequenced. Sequence analysis revealed that 28 out of 41 positive samples were Leishmania major. Thirteen sequences were unreadable and therefore not identified. CONCLUSION: At least two gerbil species common in Fars ZCL foci, M. lybicus and M. persicus, are acquiring infections of L. major and may be reservoir hosts of one predominant parasite haplotype. Most infections were detected molecularly not by conventional methods, because most rodents died in the traps.

Avalanche frontiers in the dissipative Abelian sandpile model and off-critical Schramm-Loewner evolution.

Avalanche frontiers in Abelian sandpile model (ASM) are random simple curves whose continuum limit is known to be a Schramm-Loewner evolution with diffusivity parameter κ=2. In this paper we consider the dissipative ASM and study the statistics of the avalanche and wave frontiers for various rates of dissipation. We examine the scaling behavior of a number of functions, such as the correlation length, the exponent of distribution function of loop lengths, and the gyration radius defined for waves and avalanches. We find that they do scale with the rate of dissipation. Two significant length scales are observed. For length scales much smaller than the correlation length, these curves show properties close to the critical curves, and the corresponding diffusivity parameter is nearly the same as the critical limit. We interpret this as the ultraviolet limit where κ=2 corresponding to c=-2. For length scales much larger than the correlation length, we find that the avalanche frontiers tend to self-avoiding walk, and the corresponding driving function is proportional to the Brownian motion with the diffusivity parameter κ=8/3 corresponding to a field theory with c=0. We interpret this to be the infrared limit of the theory or at least a crossover.

First-passage-time processes and subordinated Schramm-Loewner evolution.

We study the first-passage-time processes of the anomalous diffusion on the self-similar curves in two dimensions. The scaling properties of the mean-square displacement and mean first passage time of the fractional Brownian motion and subordinated walk on the different fractal curves (loop-erased random walk, harmonic explorer, and percolation front) are derived. We also define natural parametrized subordinated Schramm-Loewner evolution (NS-SLE) as a mathematical tool that can model diffusion on fractal curves. The scaling properties of the mean-square displacement and mean first passage time for NS-SLE are obtained by numerical means.

Classification of (2+1) -dimensional growing surfaces using Schramm-Loewner evolution.

Statistical behavior and scaling properties of isoheight lines in three different saturated two-dimensional grown surfaces with controversial universality classes are investigated using ideas from Schramm-Loewner evolution (SLE_{κ}). We present some evidence that the isoheight lines in the ballistic deposition (BD), Eden and restricted solid-on-solid (RSOS) models have conformally invariant properties all in the same universality class as the self-avoiding random walk (SAW), equivalently SLE_{8/3}. This leads to the conclusion that all these discrete growth models fall into the same universality class as the Kardar-Parisi-Zhang (KPZ) equation in two dimensions.