Nifurtimox plus Eflornithine for Late-Stage Sleeping Sickness in Uganda: A Case Series

African sleeping sickness (Human African Trypanosomiasis, or HAT), due to the parasite Trypanosoma brucei gambiense, threatens millions across remote and conflict-affected regions of sub-Saharan Africa, and causes about 15 000 reported cases every year. Untreated HAT progresses from stage 1 (infection of the blood and lymph) to stage 2 (invasion of the central nervous system), and ultimately death. Drugs for stage 2 are few. The historical mainstay, melarsoprol, is highly toxic and inefficacious in some areas due to parasite resistance. Eflornithine is the only viable alternative, already established as safe and efficacious, but difficult to administer and at risk of resistance if used in monotherapy. This paper reports on a series of 48 Ugandan patients treated with a novel combination of nifurtimox (a drug registered for Chagas disease) and eflornithine, 17 as part of a terminated trial, and 31 in a subsequent case series study. Despite the low sample size, findings are promising: no cases of treatment failure, no treatment terminations, and no HAT- or treatment-related deaths. Nifurtimox plus eflornithine may be the best treatment hope for stage 2 HAT patients in the next decade, while new drugs are developed. A larger, multi-centric trial of the combination is ongoing

Validity and reliability of telephone administration of the patient-specific functional scale for the assessment of recovery from snakebite envenomation

Objectives: Although more than 1.8 million people survive snakebite envenomation each year, their recovery is understudied. Obtaining long-term follow-up is challenging in both high- and low-resource settings. The Patient-Specific Functional Scale (PSFS) is an easily administered, well-accepted patient-reported outcome that is validated for assessing limb recovery from snakebite envenomation. We studied whether the PSFS is valid and reliable when administered by telephone. Methods: This is a secondary analysis of data from a randomized clinical trial. We analyzed the results of PSFS collected in-person on days 3, 7, 14, 21, and 28 and by telephone on days 10, 17, and 24. We assessed the following scale psychometric properties: (a) content validity (ceiling and floor effects), (b) internal structure and consistency (Cronbach’s alpha), and (c) temporal and external validity using Intraclass Correlation Coefficient (ICC). Temporal stability was assessed using Spearman’s correlation coefficient and agreement between adjacent in-person and telephonic assessments with Cohen’s kappa. Bland Altman analysis was used to assess differential bias in low and high score results. Results: Data from 74 patients were available for analysis. Floor effects were seen in the early post-injury time points (median: 3 (IQR: 0, 5) at 3 days post-enrollment) and ceiling effects in the late time points (median: 9 (IQR: 8, 10). Internal consistency was good to excellent with both in-person (Cronbach α: 0.91 (95%CI 0.88, 0.95)) and telephone administration (0.81 (0.73, 0.89). Temporal stability was also good (ICC: 0.83 (0.72, 0.89) in-person, 0.80 (0.68, 0.88) telephone). A strong linear correlation was found between in-person and telephone administration (Spearman’s �: 0.83 (CI: 0.78, 0.84), consistency was assessed as excellent (Cohen’s κ 0.81 (CI: 0.78, 0.84), and Bland Altman analysis showed no systematic bias. Conclusions: Telephone administration of the PSFS provides valid, reliable, and consistent data for the assessment of recovery from snakebite envenomation

Testing the Waste Based Biorefinery Concept: Pilot Scale Cultivation of Microalgal Species on Spent Anaerobic Digestate Fluids

PurposeA waste based biorefinery approach has been tested.MethodsThis has been investigated by culturing in a 800 L photobioreactor two autotrophic microalgae namely Nannochloropsis oceanica and Scenedesmus quadricauda utilising filtered spent anaerobic digestate fluids of N:P ratio 14.22 as substrate.ResultsSignificant rates of bioremediation simultaneously with biomass and associated end product formation were achieved. Nitrogen and phosphorus of waste based media was decreased up to 90%. The biomass biochemical analysis of the microalgae when grown on the waste based formulated media demonstrated the comparable content of lipids and proteins with the species grown on f/2 media.ConclusionsTheoretical biomethane potential generation, should the algal cultures be placed in an anaerobic digester, was calculated at 0.58 L CH4 g−1 VS for N. oceanica and 0.48 L CH4 g−1 VS for S. quadricauda showing comparable results with other studies of different source of biomass

Household exposure to pesticides and bladder exstrophy in a newborn baby boy: a case report and review of the literature

© 2009 Martin et al; licensee Cases Network Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Modulation of apoptosis by V protein mumps virus

<p>Abstract</p> <p>Background</p> <p>The Urabe AM9 vaccine strain of mumps virus contains two variants of V protein: VWT (of HN-A1081 viral population) and VGly (of HN-G1081). The V protein is a promoting factor of viral replication by blocking the IFN antiviral pathway.</p> <p>Findings</p> <p>We studied the relationship between V protein variants and IFN-α2b-induced apoptosis. V proteins decrease activation of the extrinsic IFN-α2b-induced apoptotic pathway monitored by the caspase 8 activity, being the effect greater with the VWT protein. Both V proteins decrease the activity of caspase 9 of the intrinsic apoptotic pathway. In a system without IFN, the VWT and VGly proteins expression promotes activation of caspases 3 and 7. However, when the cellular system was stimulated with IFN-α, this activity decreased partially. TUNEL assay shows that for treatment with IFN-α and ibuprofen of cervical adenocarcinoma cells there is nuclear DNA fragmentation but the V protein expression reduces this process.</p> <p>Conclusions</p> <p>The reduction in the levels of caspases and DNA fragmentation, suggesting that V protein, particularly VWT protein of Urabe AM9 vaccine strain, modulates apoptosis. In addition, the VWT protein shows a protective role for cell proliferation in the presence of antiproliferative signals.</p

Antagonistic Bacterial Interactions Help Shape Host-Symbiont Dynamics within the Fungus-Growing Ant-Microbe Mutualism

Conflict within mutually beneficial associations is predicted to destabilize relationships, and theoretical and empirical work exploring this has provided significant insight into the dynamics of cooperative interactions. Within mutualistic associations, the expression and regulation of conflict is likely more complex than in intraspecific cooperative relationship, because of the potential presence of: i) multiple genotypes of microbial species associated with individual hosts, ii) multiple species of symbiotic lineages forming cooperative partner pairings, and iii) additional symbiont lineages. Here we explore complexity of conflict expression within the ancient and coevolved mutualistic association between attine ants, their fungal cultivar, and actinomycetous bacteria (Pseudonocardia). Specifically, we examine conflict between the ants and their Pseudonocardia symbionts maintained to derive antibiotics against parasitic microfungi (Escovopsis) infecting the ants' fungus garden. Symbiont assays pairing isolates of Pseudonocardia spp. associated with fungus-growing ants spanning the phylogenetic diversity of the mutualism revealed that antagonism between strains is common. In contrast, antagonism was substantially less common between more closely related bacteria associated with Acromyrmex leaf-cutting ants. In both experiments, the observed variation in antagonism across pairings was primarily due to the inhibitory capabilities and susceptibility of individual strains, but also the phylogenetic relationships between the ant host of the symbionts, as well as the pair-wise genetic distances between strains. The presence of antagonism throughout the phylogenetic diversity of Pseudonocardia symbionts indicates that these reactions likely have shaped the symbiosis from its origin. Antagonism is expected to prevent novel strains from invading colonies, enforcing single-strain rearing within individual ant colonies. While this may align ant-actinomycete interests in the bipartite association, the presence of single strains of Pseudonocardia within colonies may not be in the best interest of the ants, because increasing the diversity of bacteria, and thereby antibiotic diversity, would help the ant-fungus mutualism deal with the specialized parasites

Species Richness and Range Size of the Terrestrial Mammals of the World: Biological Signal within Mathematical Constraints

We explore global spatial diversity patterns for terrestrial mammals using as a tool range-diversity plots. These plots display simultaneously information about the number of species in localities and their spatial covariance in composition. These are highly informative, as we show by linking range-diversity plots with maps and by highlighting the correspondences between well defined regions of the plots with geographical regions or with taxonomic groups. Range-diversity plots are mathematically constrained by the lines of maximum and minimum mean covariance in species composition. We show how regions in the range-diversity plot corresponding to the line of maximum covariance correspond to large continental masses, and regions near the lower limit of the range-diversity plot correspond to archipelagos and mountain ranges. We show how curves of constant covariance correspond to nested faunas. Finally, we show that the observed distribution of the covariance range has significantly longer tails than random, with clear geographic correspondences. At the scale of our data we found that range-diversity plots reveal biodiversity patterns that cannot be replicated by null models, and correspond to conspicuous terrain features and taxonomic groupings

Measuring Adherence to Inhaled Control Medication in Patients with Asthma: Comparison Among an Asthma App, Patient Self‐Report and Physician Assessment

Background: Previous studies have demonstrated the feasibility of using an asthma app to support medication management and adherence but failed to compare with other measures currently used in clinical practice. However, in a clinical setting, any additional adherence measurement must be evaluated in the context of both the patient and physician perspectives so that it can also help improve the process of shared decision making. Thus, we aimed to compare different measures of adherence to asthma control inhalers in clinical practice, namely through an app, patient self-report and physician assessment. Methods: This study is a secondary analysis of three prospective multicentre observational studies with patients (≥13 years old) with persistent asthma recruited from 61 primary and secondary care centres in Portugal. Patients were invited to use the InspirerMundi app and register their inhaled medication. Adherence was measured by the app as the number of doses taken divided by the number of doses scheduled each day and two time points were considered for analysis: 1-week and 1-month. At baseline, patients and physicians independently assessed adherence to asthma control inhalers during the previous week using a Visual Analogue Scale (VAS 0-100). Results: A total of 193 patients (72% female; median [P25-P75] age 28 [19-41] years old) were included in the analysis. Adherence measured by the app was lower (1 week: 31 [0-71]%; 1 month: 18 [0-48]%) than patient self-report (80 [60-95]) and physician assessment (82 [51-94]) (p 0.05). There was a moderate correlation between patient self-report and physician assessment (ρ = 0.596, p < 0.001). Conclusions: Adherence measured by the app was lower than that reported by the patient or the physician. This was expected as objective measurements are commonly lower than subjective evaluations, which tend to overestimate adherence. Nevertheless, the low adherence measured by the app may also be influenced by the use of the app itself and this needs to be considered in future studies.info:eu-repo/semantics/publishedVersio

Autoinhibition of TBCB regulates EB1-mediated microtubule dynamics

Tubulin cofactors (TBCs) participate in the folding, dimerization, and dissociation pathways of the tubulin dimer. Among them, TBCB and TBCE are two CAP-Gly domain-containing proteins that interact and dissociate the tubulin dimer. Here we show how TBCB localizes at spindle and midzone microtubules during mitosis. Furthermore, the motif DEI/M-COO– present in TBCB, which is similar to the EEY/F-COO– element characteristic of EB proteins, CLIP-170, and α-tubulin, is required for TBCE–TBCB heterodimer formation and thus for tubulin dimer dissociation. This motif is responsible for TBCB autoinhibition, and our analysis suggests that TBCB is a monomer in solution. Mutants of TBCB lacking this motif are derepressed and induce microtubule depolymerization through an interaction with EB1 associated to microtubule tips. TBCB is also able to bind to the chaperonin complex CCT containing α-tubulin, suggesting that it could escort tubulin to facilitate its folding and dimerization, recycling or degradation