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Background. The treatment of cutaneous leishmaniasis (CL) caused by leishmania braziliensis in Brazil with pentavalent antimony (Sb) is associated with a high rate of failure, up to 45% of cases. In addition, Sb can only administered parenterally and has important toxic effect. An effective, safe, and oral treatment for CL is required. Methods. A randomized controlled clinical trial was conducted to compare the efficacy and safety of high-dosage oral fluconazole (6.5–8.0 mg/kg/d for 28 days) versus a standard Sb protocol (20 mg/kg/d for 20 days) for the treatment of CL in Bahia, Brazil. Results. A total of 53 subjects were included in the trial; 26 were treated with Sb, and 27 with fluconazole. Intention-to-treat analysis showed initial cure rates (2 months after treatment) of 22.2% (6 of 27) in the fluconazole and 53.8% (14 of 26) in the Sb group (P = .04). Six months after treatment, the final cure rate remained the same in both groups, without any replaces. The frequencies of adverse effects in the Sb and fluconazole groups were similar, 34.6% versus 37% respectively. One patient treated with fluconazole discontinued treatment owing to malaise, headache, and moderate dizziness (Common Terminology Criteria for Adverse Events grade 2). Conclusions. Oral fluconazole at a dosage of 6.5–8 mg/kg/d for 28 days should not be considered an effective treatment for CL caused by L. braziliensis. Clinical Trials Registration. NCT01953744.

The mainstays of cutaneous leishmaniasis (CL) treatment, in several world regions, are pentavalent antimony (Sbv) compounds administered parenterally, despite their recognized toxicity, which requires frequent laboratory monitoring and complicates their use in areas with scarce infrastructure. As result of these drawbacks, the WHO Expert Committee on leishmaniasis has expanded the recommendations for the use of local therapies, including Sbv intralesional infiltration (IL-Sbv), as CL therapy alternatives even in the New World. However, the efficacy of these approaches has never been compiled. The aim of this study was to critically and systematically assess the efficacy of IL-Sbv for CL treatment. The PRISMA guidelines for systematic reviews and the Cochrane manual were followed. The sources used were the MEDLINE and LILACS databases and the International Clinical Trials Registry Platform of the World Health Organization. The outcome of interest was a clinical cure, defined as complete re-epithelialization of all lesions. The IL-Sbv pooled cure rate was estimated for several subgroups and direct comparisons were performed when possible. Thirty nine articles (40 studies) involving 5679 patients treated with IL-Sbv infiltration were included. In direct comparison, only three studies involving 229 patients compared IL-Sbv infiltration versus placebo and no difference was observed (OR: 1,9; 95%IC 0,93 to 3,82) based on cure rate 69.6% (95%CI 17.6-96.1%) and 83,2% (95%CI 66-92.7%) for placebo and IL-Sbv, respectively. In an alternative and non-comparative analysis, gathering all study arms using the intervention, the pooled IL-Sbv efficacy rate was 75% (95%CI 68-81%). In the Old World, the observed overall IL-Sbv efficacy rate was 75% (95%CI 66-82%), and the cure rates were significantly higher with sodium stibogluconate (SSG) than with meglumine antimoniate (MA): 83% (95%CI 75-90%) versus 68% (95%CI 54-79%), p = 0.03. Studies directly comparing IL-Sbv with topical 15% paromomycin ointment, IL hypertonic saline, radiofrequency-induced heat therapy, topical trichloroacetic acid and cryotherapy showed no significant difference in efficacy between the interventions. The analyses suggested a higher efficacy of IL-Sbv combined with cryotherapy (81.8%, 95%IC 62.4-92.4%) when compared with IL-Sbv alone (53.3%, 95%IC 46.1-66%), OR: 3.14 (95%CI 1.1-8.9), p = 0.03. In the New World, the global IL-Sbv efficacy was 77%(95%CI 66-85%). In contrast with the Old World, a significant difference favoring MA in relation to SSG was observed: 61% (95%CI 49-73%) versus 82% (95%CI 70-89%).By comparing IL infiltration schedules, it was determined that patients submitted to IL-Sbv treatments longer than 14 days had higher cure rates. Despite the high heterogeneity and low methodological quality of studies, an indirect comparison shows that the antimony infiltration efficacy rate is similar to that reported for antimony systemic use. The evidence gathered thus far is insufficient to identify the ideal IL therapeutic regime or estimate the rates of adverse events and mucosal late complications.

Operation speed is a key challenge in phase-change random-access memory (PCRAM) technology, especially for achieving subnanosecond high-speed cache memory. Commercialized PCRAM products are limited by the tens of nanoseconds writing speed, originating from the stochastic crystal nucleation during the crystallization of amorphous germanium antimony telluride (Ge₂Sb₂Te₅). Here, we demonstrate an alloying strategy to speed up the crystallization kinetics. The scandium antimony telluride (Sc0.2Sb₂Te₃) compound that we designed allows a writing speed of only 700 picoseconds without preprogramming in a large conventional PCRAM device. This ultrafast crystallization stems from the reduced stochasticity of nucleation through geometrically matched and robust scandium telluride (ScTe) chemical bonds that stabilize crystal precursors in the amorphous state. Controlling nucleation through alloy design paves the way for the development of cache-type PCRAM technology to boost the working efficiency of computing systems.

The reaction between methylammonium iodide ( MAI ( MA = CH 3 NH 3 + ) ) and antimony sulfoiodide ( SbSI ) in reflux conditions results in the formation of a 2D-layered perovskite phase, methylammonium antimony iodide ( MA 3 Sb 2 I 9 ). X-ray diffraction XRD and UV - Vis spectroscopy confirm that in reflux conditions, the reaction between MAI and SbSI in a 2:7 molar ratio (MR(2:7)) obtains the 2 D -layered MA 3 Sb 2 I 9 lead-free perovskite phase as the main product. The MR(2:7) MAI - SbSI reaction product in a carbon matrix in lateral electrode configuration exhibits a relatively high difference between light and dark current I light - I dark of ~ 55 µA at 1 V applied bias voltage. The better photoresponse for the MR(2:7) MAI - SbSI reaction product in the presented device configuration indicates that the lead-free 2D-layered perovskite structure ( MA 3 Sb 2 I 9 ) found assistance from the carbon materials for improved photogenerated charge carrier harvesting.

Microorganisms play crucial roles in phosphorus (P) turnover and P bioavailability increases in heavy metal-contaminated soils. However, microbially driven P-cycling processes and mechanisms of their resistance to heavy metal contaminants remain poorly understood. Here, we examined the possible survival strategies of P-cycling microorganisms in horizontal and vertical soil samples from the world’s largest antimony (Sb) mining site, which is located in Xikuangshan, China. We found that total soil Sb and pH were the primary factors affecting bacterial community diversity, structure and P-cycling traits. Bacteria with the gcd gene, encoding an enzyme responsible for gluconic acid production, largely correlated with inorganic phosphate (Pi) solubilization and significantly enhanced soil P bioavailability. Among the 106 nearly complete bacterial metagenome-assembled genomes (MAGs) recovered, 60.4% carried the gcd gene. Pi transportation systems encoded by pit or pstSCAB were widely present in gcd -harboring bacteria, and 43.8% of the gcd -harboring bacteria also carried the acr3 gene encoding an Sb efflux pump. Phylogenetic and potential horizontal gene transfer (HGT) analyses of acr3 indicated that Sb efflux could be a dominant resistance mechanism, and two gcd -harboring MAGs appeared to acquire acr3 through HGT. The results indicated that Sb efflux could enhance P cycling and heavy metal resistance in Pi-solubilizing bacteria in mining soils. This study provides novel strategies for managing and remediating heavy metal-contaminated ecosystems.

Alternative treatments for visceral leishmaniasis (VL) are required in East Africa. Paromomycin sulphate (PM) has been shown to be efficacious for VL treatment in India. A multi-centre randomized-controlled trial (RCT) to compare efficacy and safety of PM (20 mg/kg/day for 21 days) and PM plus sodium stibogluconate (SSG) combination (PM, 15 mg/kg/day and SSG, 20 mg/kg/day for 17 days) with SSG (20 mg/kg/day for 30 days) for treatment of VL in East Africa. Patients aged 4-60 years with parasitologically confirmed VL were enrolled, excluding patients with contraindications. Primary and secondary efficacy outcomes were parasite clearance at 6-months follow-up and end of treatment, respectively. Safety was assessed mainly using adverse event (AE) data. The PM versus SSG comparison enrolled 205 patients per arm with primary efficacy data available for 198 and 200 patients respectively. The SSG & PM versus SSG comparison enrolled 381 and 386 patients per arm respectively, with primary efficacy data available for 359 patients per arm. In Intention-to-Treat complete-case analyses, the efficacy of PM was significantly lower than SSG (84.3% versus 94.1%, difference = 9.7%, 95% confidence interval, CI: 3.6 to 15.7%, p = 0.002). The efficacy of SSG & PM was comparable to SSG (91.4% versus 93.9%, difference = 2.5%, 95% CI: -1.3 to 6.3%, p = 0.198). End of treatment efficacy results were very similar. There were no apparent differences in the safety profile of the three treatment regimens. The 17 day SSG & PM combination treatment had a good safety profile and was similar in efficacy to the standard 30 day SSG treatment, suggesting suitability for VL treatment in East Africa. www.clinicaltrials.govNCT00255567.

SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa. A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three treatment regimens: 10 mg/kg single dose AmBisome plus 10 days of SSG (20 mg/kg/day), 10 mg/kg single dose AmBisome plus 10 days of miltefosine (2.5mg/kg/day) and miltefosine alone (2.5 mg/kg/day for 28 days). The primary endpoint was initial parasitological cure at Day 28, and secondary endpoints included definitive cure at Day 210, and pharmacokinetic (miltefosine) and pharmacodynamic assessments. In sequential analyses with 49-51 patients per arm, initial cure was 85% (95% CI: 73-92) in all arms. At D210, definitive cure was 87% (95% CI: 77-97) for AmBisome + SSG, 77% (95% CI 64-90) for AmBisome + miltefosine and 72% (95% CI 60-85) for miltefosine alone, with lower efficacy in younger patients, who weigh less. Miltefosine pharmacokinetic data indicated under-exposure in children compared to adults. No major safety concerns were identified, but point estimates of definitive cure were less than 90% for each regimen so none will be evaluated in Phase III trials in their current form. Allometric dosing of miltefosine in children needs to be evaluated. The study was registered with ClinicalTrials.gov, number NCT01067443.

Arsenic and antimony are metalloids with profound effects on biological systems and human health. Both elements are toxic to cells and organisms, and exposure is associated with several pathological conditions including cancer and neurodegenerative disorders. At the same time, arsenic- and antimony-containing compounds are used in the treatment of multiple diseases. Although these metalloids can both cause and cure disease, their modes of molecular action are incompletely understood. The past decades have seen major advances in our understanding of arsenic and antimony toxicity, emphasizing genotoxicity and proteotoxicity as key contributors to pathogenesis. In this review, we highlight mechanisms by which arsenic and antimony cause toxicity, focusing on their genotoxic and proteotoxic effects. The mechanisms used by cells to maintain proteostasis during metalloid exposure are also described. Furthermore, we address how metalloid-induced proteotoxicity may promote neurodegenerative disease and how genotoxicity and proteotoxicity may be interrelated and together contribute to proteinopathies. A deeper understanding of cellular toxicity and response mechanisms and their links to pathogenesis may promote the development of strategies for both disease prevention and treatment.

Antimony has been known and used since ancient times, but its applications have increased significantly during the last two centuries. Aside from its few medical applications, it also has industrial applications, acting as a flame retardant and a catalyst. Geologically, native antimony is rare, and it is mostly found in sulfide ores. The main ore minerals of antimony are antimonite and jamesonite. The extensive mining and use of antimony have led to its introduction into the biosphere, where it can be hazardous, depending on its bioavailability and absorption. Detailed studies exist both from active and abandoned mining sites, and from urban settings, which document the environmental impact of antimony pollution and its impact on human physiology. Despite its evident and pronounced toxicity, it has also been used in some drugs, initially tartar emetics and subsequently antimonials. The latter are used to treat tropical diseases and their therapeutic potential for leishmaniasis means that they will not be soon phased out, despite the fact the antimonial resistance is beginning to be documented. The mechanisms by which antimony is introduced into human cells and subsequently excreted are still the subject of research; their elucidation will enable us to better understand antimony toxicity and, hopefully, to improve the nature and delivery method of antimonial drugs.

Antimony selenide (Sb 2 Se 3 ) has a one-dimensional (1D) crystal structure comprising of covalently bonded (Sb 4 Se 6 ) n ribbons stacking together through van der Waals force. This special structure results in anisotropic optical and electrical properties. Currently, the photovoltaic device performance is dominated by the grain orientation in the Sb 2 Se 3 thin film absorbers. Effective approaches to enhance the carrier collection and overall power-conversion efficiency are urgently required. Here, we report the construction of Sb 2 Se 3 solar cells with high-quality Sb 2 Se 3 nanorod arrays absorber along the [001] direction, which is beneficial for sun-light absorption and charge carrier extraction. An efficiency of 9.2%, which is the highest value reported so far for this type of solar cells, is achieved by junction interface engineering. Our cell design provides an approach to further improve the efficiency of Sb 2 Se 3 -based solar cells. Antimony selenide is a promising thin film solar cell absorber material in which grain orientation is crucial for high device performance. Here Li et al. grow the material in nanorod arrays along the [001] direction and obtain record high efficiency of 9.2%.