763 research outputs found
Switchable Adhesion of Soft Composites Induced by a Magnetic Field
Switchable adhesives have the potential to improve the manufacturing and
recycling of parts and to enable new modes of motility for soft robots. Here,
we demonstrate magnetically-switchable adhesion of a two-phase composite to
non-magnetic objects. The composite's continuous phase is a silicone elastomer,
and the dispersed phase is a magneto-rheological fluid. The composite is simple
to prepare, and to mould to different shapes. When a magnetic field is applied,
the magneto-rheological fluid develops a yield stress, which dramatically
enhances the composite's adhesive properties. We demonstrate up to a nine-fold
increase of the pull-off force of non-magnetic objects in the presence of a 250
mT field
Risk factors of visceral leishmaniasis in East Africa: a case-control study in Pokot territory of Kenya and Uganda
BACKGROUND: In East Africa, visceral leishmaniasis (VL) is endemic in parts of Sudan, Ethiopia, Somalia, Kenya and Uganda. It is caused by Leishmania donovani and transmitted by the sandfly vector Phlebotomus martini. In the Pokot focus, reaching from western Kenya into eastern Uganda, formulation of a prevention strategy has been hindered by the lack of knowledge on VL risk factors as well as by lack of support from health sector donors. The present study was conducted to establish the necessary evidence-base and to stimulate interest in supporting the control of this neglected tropical disease in Uganda and Kenya. METHODS: A case-control study was carried out from June to December 2006. Cases were recruited at Amudat hospital, Nakapiripirit district, Uganda, after clinical and parasitological confirmation of symptomatic VL infection. Controls were individuals that tested negative using a rK39 antigen-based dipstick, which were recruited at random from the same communities as the cases. Data were analysed using conditional logistic regression. RESULTS: Ninety-three cases and 226 controls were recruited into the study. Multivariate analysis identified low socio-economic status and treating livestock with insecticide as risk factors for VL. Sleeping near animals, owning a mosquito net and knowing about VL symptoms were associated with a reduced risk of VL. CONCLUSIONS: VL affects the poorest of the poor of the Pokot tribe. Distribution of insecticide-treated mosquito nets combined with dissemination of culturally appropriate behaviour-change education is likely to be an effective prevention strategy
Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: confirmation from a multinational study (IMPAMEL II).
BACKGROUND: Treatment of late-stage human African trypanosomiasis (HAT) with melarsoprol can be improved by shortening the regimen. A previous trial demonstrated the safety and efficacy of a 10-day treatment schedule. We demonstrate the effectiveness of this schedule in a noncontrolled, multinational drug-utilization study. METHODS: A total of 2020 patients with late-stage HAT were treated with the 10-day melarsoprol schedule in 16 centers in 7 African countries. We assessed outcome on the basis of major adverse events and the cure rate after treatment and during 2 years of follow-up. RESULTS: The cure rate 24 h after treatment was 93.9%; 2 years later, it was 86.2%. However, 49.3% of patients were lost to follow-up. The overall fatality rate was 5.9%. Of treated patients, 8.7% had an encephalopathic syndrome that was fatal 45.5% of the time. The rate of severe bullous and maculopapular eruptions was 0.8% and 6.8%, respectively. CONCLUSIONS: The 10-day treatment schedule was well implemented in the field and was effective. It reduces treatment duration, drug amount, and hospitalization costs per patient, and it increases treatment-center capacity. The shorter protocol has been recommended by the International Scientific Council for Trypanosomiasis Research and Control for the treatment of late-stage HAT caused by Trypanosoma brucei gambiense
Proteolytic Cleavage of a Spectrin-Related Protein by Calcium-Dependent Protease in Neurospora crassa
To investigate the functional significance of a cytoskeletal spectrin-like protein, we studied its localization pattern in Neurospora crassa and sought the answer to whether it is a substrate for another apically localized protein, the calcium-dependent protease (CDP II). Immunoblots of crude extracts from exponentially growing mycelia, separated by one- and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis using antichicken α/β-spectrin antibodies, revealed a single band of approximately relative mass (Mr) 100 kDa with an isoeletric point (pI) in the range of 6.5 to 7.0. Despite rigorous efforts, we could not confirm the presence of an Mr 240- to 220-kDa spectrin-like protein in N. crassa. The immunofluorescence- and immunogold-labeling Mr 100-kDa protein showed its predominance along the plasma membrane of the conidia during the swelling phase of germination. In contrast, in the germ tubes and the growing hyphae, the localization was polarized and concentrated mainly in the apical region. The in vitro proteolysis experiments showed that indeed this protein is a preferred substrate of CDP II which is, as mentioned previously, also localized in the apical regions of the hyphae. These results indicate a putative functional relationship between these two proteins (spectrin-like protein and CDP II) in the dynamics of tip growt
Sodium stibogluconate cardiotoxicity and safety of generics
Between April 9 and May 5 2000, an outbreak of fatal cardiotoxicity occurred in Nepal amongst visceralleishmaniasis patients treated with a recently introduced batch of generic sodium stibogluconate (SSG) from GL Pharmaceuticals, Calcutta, India. Eight (36%) of 23 patients treated with this batch died, and in 5 (23%) death was attributed to the cardiotoxicity of the drug. This contrasts with the low total death rate (3.2%) and death rate due to cardiotoxicity (0.8%) observed among 252 patients treated between August 1999 and December 2001 with generic SSG from Albert David Ltd, Calcutta, India. These data show that every batch of generic SSG should be subject to rigorous quality control prior to us
Validation of Two Rapid Diagnostic Tests for Visceral Leishmaniasis in Kenya
BACKGROUND: Visceral leishmaniasis (VL) is a systemic parasitic disease that is fatal unless treated. In Kenya, national VL guidelines rely on microscopic examination of spleen aspirate to confirm diagnosis. As this procedure is invasive, it cannot be safely implemented in peripheral health structures, where non-invasive, accurate, easy to use diagnostic tests are needed. METHODOLOGY: We evaluated the sensitivity, specificity and predictive values of two rapid diagnostic tests (RDT), DiaMed IT LEISH and Signal-KA, among consecutive patients with clinical suspicion of VL in two treatment centres located in Baringo and North Pokot District, Rift Valley province, Kenya. Microscopic examination of spleen aspirate was the reference diagnostic standard. Patients were prospectively recruited between May 2010 and July 2011. PRINCIPAL FINDINGS: Of 251 eligible patients, 219 patients were analyzed, including 131 VL and 88 non-VL patients. The median age of VL patients was 16 years with predominance of males (66%). None of the tested VL patients were co-infected with HIV. Sensitivity and specificity of the DiaMed IT LEISH were 89.3% (95%CI: 82.7-94%) and 89.8% (95%CI: 81.5-95.2%), respectively. The Signal KA showed trends towards lower sensitivity (77.1%; 95%CI: 68.9-84%) and higher specificity (95.5%; 95%CI: 88.7-98.7%). Combining the tests did not improve the overall diagnostic performance, as all patients with a positive Signal KA were also positive with the DiaMed IT LEISH. CONCLUSION/SIGNIFICANCE: The DiaMed IT LEISH can be used to diagnose VL in Kenyan peripheral health facilities where microscopic examination of spleen aspirate or sophisticated serological techniques are not feasible. There is a crucial need for an improved RDT for VL diagnosis in East Africa
Arsenic exposure and outcomes of antimonial treatment in visceral leishmaniasis patients in bihar, India:a retrospective cohort study
Funding: This work was supported by a Clinical PhD Fellowship to MRP (090665) and a Principal Research Fellowship to AHF (079838) from the Wellcome Trust (http://www.wellcome.ac.uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD
Clinical risk factors for therapeutic failure in kala-azar patients treated with pentavalent antimonials in Nepal
Drug-related factors and parasite resistance have been implicated in the failure of pentavalent antimonials (Sbv) in the Indian subcontinent; however, little information is available on host-related factors. Parasitologically confirmed kala-azar patients, treatment naïve to Sbv, were prospectively recruited at a referral hospital in Nepal and were treated under supervision with 30 doses of quality-assured sodium stibogluconate (SSG) 20 mg/kg/day and followed for 12 months to assess cure. Analysis of risk factors for treatment failure was assessed in those receiving ≥25 doses and completing 12 months of follow-up. One hundred and ninety-eight cases were treated with SSG and the overall cure rate was 77.3% (153/198). Of the 181 cases who received ≥25 doses, 12-month follow-up data were obtained in 169, comprising 153 patients (90.5%) with definite cure and 16 (9.5%) treatment failures. In the final logistic regression model, increased failure to SSG was significantly associated with fever for ≥12 weeks [odds ratio (OR) = 7.4], living in districts bordering the high SSG resistance zone in Bihar (OR = 6.1), interruption of treatment (OR = 4.3) and ambulatory treatment (OR = 10.2). Early diagnosis and supervised treatment is of paramount importance to prevent treatment failures within the control programm
Treatment of visceral leishmaniasis in south-eastern Nepal: decreasing efficacy of sodium stibogluconate and need for a policy to limit further decline
Sodium stibogluconate (SSG) is the first-line therapy for visceral leishmaniasis (VL) in south-eastern Nepal. Recent studies from the neighbouring state of Bihar, India, have shown a dramatic fall in cure rates with treatment failure occurring in up to 65% of VL patients treated with SSG. A prospective study was conducted at a tertiary-level hospital located in south-eastern Nepal from July 1999 to January 2001. Parasitologically proven kala-azar patients with no previous history of treatment for VL were treated with SSG 20 mg/kg/d for 30 d which was extended to 40 d in those with persistent positive parasitology. Of the 110 patients who completed SSG therapy and were assessed at 1 and 6 months, definite cure was achieved in 99 patients (90%) and SSG failure occurred in 11 patients (10%). Except for the presence of hepatomegaly and a lower platelet count there was no clinical or laboratory baseline characteristic associated with treatment failure. A significantly lower cure rate (76%, P = 0.03) was observed in patients from the district of Saptari, which borders the antimony-resistant VL areas of Bihar. The efficacy of SSG as a first-line treatment for VL in south-eastern Nepal was still satisfactory, except for the patients living closer to the antimony-resistant VL areas of India. These findings indicate that the spread of resistance to antimonials is already taking place in Nepal and that a policy to control further spread should be urgently implemente
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