Investigating the relationship between multiple sclerosis disability and driving performance: A comparative study of the multiple sclerosis functional composite and expanded disability status scale.

INTRODUCTION: Multiple Sclerosis (MS) can affect the ability to perform complex tasks such as driving. The Expanded Disability Status Scale (EDSS) overlooks cognitive deficits crucial for driving. We investigated the relationship between the Multiple Sclerosis Functional Composite (MSFC), which includes cognitive assessment, and EDSS in relation to driving performance. METHODS:  This exploratory study involved 30 MS patients (mean EDSS 2.4 ± 2.0) and 15 healthy controls. We correlated the results of the EDSS, MSFC, and driving performance tests, namely the Two-Hand Coordination Test (2HAND) and the Speed Anticipation Reaction Test (SART). RESULTS: Patients did not differ from the healthy controls regarding age, sex, and driving experience. However, they exhibited lower mean Z-scores in MSFC, particularly in motor domains, but not in cognitive function. The mean Z-score for the 25-foot Walk test was -0.42 in patients compared to -0.04 in controls. For the 9-hole Peg Test, it was 0.17 in patients versus 1.47 in controls. Patients had a mean total error time of 19.7 seconds for both hands in the 2HAND test, compared to 7.7 seconds in controls. In MS patients, the MSFC and EDSS significantly correlated with SART and 2HAND components. While upper limb function (9-HPT) did not correlate with 2HAND, cognitive function (PASAT) did correlate with the number of 2HAND errors, indicating that cognitive dysfunction impacts driving performance more than physical dysfunction. CONCLUSION: The MSFC may provide valuable insights into the driving abilities of MS patients, potentially offering advantages over the EDSS in predicting driving performance. Further research with larger, more diverse populations across various driving environments is necessary to validate these findings.

The influence of frequency, volume, and viscosity on the ultrasonic atomization threshold of sessile droplets.

In this research, we present a study on the atomization threshold (ATh) of sessile droplets, analyzing its relationship with the excitation frequency fexc (55-48 kHz), droplet volume Vdrop (1-100 µl), and droplet viscosity µ (1-6 mPa⋅s). The investigation focused on the atomization thresholds using ultrasonic excitation of distilled water droplets and water- polyethylene glycol (PEG)-8000 mixtures deposited on vibrating surfaces. The obtained results are compared with previously reported theoretical models. A modification to the model proposed by Alzuaga et al. [Alzuaga, Manceau, and Bastien, J. Sound Vib. 282(1-2), 151-162 (2005)] is suggested to determine the atomization thresholds of sessile droplets, incorporating the atomization droplet size equation proposed by Rajan and Pandit and an empirical constant α to account for the effect of droplet volume in this process. The results show that the relationship between the atomization threshold and viscosity does not fit well with the prediction of Eisenmenger [Acta Acust united Acust. 9(4), 327-340 (1959)] and Pohlman and Stamm [Untersuchung Zum Mechanismus Der Ultraschallvernebelung an Flüssigkeitsoberflächen im Hinblick Auf Technische Anwendungen (Investigation on the Mechanism of Ultrasonic Nebulization on Liquid Surfaces Considering Technical Applications) (VS Verlag für Sozialwissenschaften, Wiesbaden, Germany, 1965)] and Pohlman et al. [Pohlman, Heisler, and Cichos, Ultrasonicc 12(1), 11-15 (1974)] (ATh∝µ). However, the data tendency aligns with the model proposed by Alzuaga (ATh ∝ µ1/2). The results obtained in this study provide a deeper understanding of the atomization thresholds of sessile droplets through ultrasonic excitation.

Characterization of Novel Trypanosoma cruzi-Specific Antigen with Potential Use in the Diagnosis of Chagas Disease.

Chagas disease is caused by the parasite Trypanosoma cruzi. In humans, it evolves into a chronic disease, eventually resulting in cardiac, digestive, and/or neurological disorders. In the present study, we characterized a novel T. cruzi antigen named Tc323 (TcCLB.504087.20), recognized by a single-chain monoclonal antibody (scFv 6B6) isolated from the B cells of patients with cardiomyopathy related to chronic Chagas disease. Tc323, a ~323 kDa protein, is an uncharacterized protein showing putative quinoprotein alcohol dehydrogenase-like domains. A computational molecular docking study revealed that the scFv 6B6 binds to an internal domain of Tc323. Immunofluorescence microscopy and Western Blot showed that Tc323 is expressed in the main developmental forms of T. cruzi, localized intracellularly and exhibiting a membrane-associated pattern. According to phylogenetic analysis, Tc323 is highly conserved throughout evolution in all the lineages of T. cruzi so far identified, but it is absent in Leishmania spp. and Trypanosoma brucei. Most interestingly, only plasma samples from patients infected with T. cruzi and those with mixed infection with Leishmania spp. reacted against Tc323. Collectively, our findings demonstrate that Tc323 is a promising candidate for the differential serodiagnosis of chronic Chagas disease in areas where T. cruzi and Leishmania spp. infections coexist.

Changes in the Expression of TGF-Beta Regulatory Pathway Genes Induced by Vitamin D in Patients with Relapsing-Remitting Multiple Sclerosis.

Vitamin D is an environmental factor related to multiple sclerosis that plays a significant role in immune regulation. TGF-ß is a superfamily of cytokines with an important dual effect on the immune system. TGF-ß inhibits the Th1 response while facilitating the preservation of regulatory T cells (FOXP3+) in an immunoregulatory capacity. However, when IL-6 is present, it stimulates the Th17 response. Our aim was to analyze the regulatory effect of vitamin D on the in vivo TGF-ß signaling pathway in patients with relapsing-remitting multiple sclerosis (RRMS). A total of 21 patients with vitamin D levels < 30 ng/mL were recruited and supplemented with oral vitamin D. All patients were receiving disease-modifying therapy, with the majority being on natalizumab. Expression of SMAD7, ERK1, ZMIZ1, BMP2, BMPRII, BMP4, and BMP5 was measured in CD4+ lymphocytes isolated from peripheral blood at baseline and one and six months after supplementation. SMAD7 was overexpressed at six months with respect to baseline and month one. ERK1 was overexpressed at six months with respect to month one of treatment. No significant differences in expression were observed for the remaining genes. No direct correlation was found with serum vitamin D levels. BMPRII expression changed differentially in non-natalizumab- versus natalizumab-treated patients. Changes were observed in the expression of ERK1, BMP2, and BMP5 based on disease activity measured using the Rio-Score, BMP2 in patients who had relapses, and BMP5 in those whose EDSS worsened. Our results suggest indirect regulation of vitamin D in TGF-ß pathway genes in patients with RRMS.

IgE antibodies against Trypanosoma cruzi arginine kinase in patients with chronic Chagas disease.

Arginine kinase (AK) is an enzyme present in various invertebrates, as well as in some trypanosomatids such as T. cruzi, the etiological agent that causes Chagas disease. In invertebrates, this protein acts as an allergen inducing an IgE-type humoral immune response. Since AK is a highly conserved protein, we decided to study whether patients with chronic Chagas disease (CCD) produce specific antibodies against T. cruzi AK (TcAK). Plasma from patients with CCD, with and without cardiac alterations and non-infected individuals were evaluated for the presence of anti-TcAK IgG and IgE antibodies by ELISA, including detection of specific IgG subclasses. Our results showed that the levels of specific anti-TcAK IgG and IgE were different between infected and non-infected individuals, but comparable between those with different clinical manifestations. Interestingly, anti-TcAK IgG4 antibodies associated with IgE-mediated allergenic processes were also increased in CCD patients. Finally, we found that several of the predicted B cell epitopes in TcAK matched allergenic peptides previously described for its homologues in other organisms. Our results revealed for the first time a parasite's specific IgE antibody target and suggest that TcAK could contribute to delineate an inefficient B cell response by prompting a bias towards a Th2 profile. These findings also shed light on a potential allergenic response in the context of T. cruzi infection.

Ex vivo characterization of Breg cells in patients with chronic Chagas disease.

Despite the growing importance of the regulatory function of B cells in many infectious diseases, their immunosuppressive role remains elusive in chronic Chagas disease (CCD). Here, we studied the proportion of different B cell subsets and their capacity to secrete IL-10 ex vivo in peripheral blood from patients with or without CCD cardiomyopathy. First, we immunophenotyped peripheral blood mononuclear cells from patients according to the expression of markers CD19, CD24, CD38 and CD27 and we showed an expansion of total B cell and transitional CD24highCD38high B cell subsets in CCD patients with cardiac involvement compared to non-infected donors. Although no differences were observed in the frequency of total IL-10 producing B cells (B10) among the groups, CCD patients with cardiac involvement showed an increased proportion of naïve B10 cells and a tendency to a higher frequency of transitional B10 cells compared to non-infected donors. Our research demonstrates that transitional B cells are greatly expanded in patients with the cardiac form of CCD and these cells retain the ability to secrete IL-10. These findings provide insight into the phenotypic distribution of regulatory B cells in CCD, an important step towards new strategies to prevent cardiomyopathy associated with T. cruzi infection.

Effect of preoperative exercise on vascular caliber and maturation of arteriovenous fistula: the physicalfav trial, a randomized controlled study.

BACKGROUND AND OBJECTIVES: Autologous arteriovenous fistula (AVF) is the best vascular access for hemodialysis. Distal forearm radiocephalic fistula is the best option, although the primary failure rate ranges from 20% to 50%. The main objective of the PHYSICALFAV trial was to evaluate the effect of preoperative isometric exercise on vascular caliber, percentage of distal arteriovenous fistula, and primary failure rate. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The PHYSICALFAV trial (NCT03213756) is an open-label, multicenter, prospective, randomized, controlled trial (RCT). A total of 138 patients were randomized 1:1 to the exercise group (exercises combining a handgrip device and an elastic band for 8 weeks) or the control group (no exercise) and followed up with periodic Doppler ultrasound (DU) examinations. RESULTS: After 8 weeks of preoperative isometric exercise, in the exercise group, significant increases were detected in venous caliber (2.80 ± 0.95 mm vs 3.52 ± 0.93 mm [p < 0.001]), arterial caliber (2.61 ± 0.82 mm vs 2.74 ± 0.80 mm [p = 0.008]), arterial peak systolic velocity (66.34 ± 19.2 cm/s vs 71.03 ± 21.5 cm/s [p 0.043]), and maximum strength (28.35 ± 9.16 kg vs 32.68 ± 10.8 kg [p < 0.001]). Distal radiocephalic fistulas were performed in 75% of the exercise group patients compared with 50.8% in the control group (p = 0.030). The global primary failure rate was very low in both groups (7% exercise group vs 14% control group [p = 0.373]). CONCLUSION: Isometric preoperative exercise can improve vascular caliber and increase the possibility of performing distal arteriovenous fistula, with no significant differences in primary failure rate.

Predicting conversion to multiple sclerosis by assessing cognitive impairment in radiologically isolated syndrome.

Up to a third of patients with radiologically isolated syndrome (RIS) exhibit lower-than-expected cognitive performances in neuropsychological evaluations, but the relationship between cognitive impairment (CI) and quantitative magnetic resonance (MRI) measures has not been stablished. Furthermore, the prognostic role of CI in RIS for conversion to MS is currently unknown. We assessed 17 patients with RIS and 17 matched healthy controls (HC) with a neurophychological battery and a 3T MRI. Six patients (35,3%) fulfilled our criterion for CI (scores 2 SDs below the mean of HC in at least two cognitive tests) (ci-RIS). The ci-RIS subgroup showed lower values of normalized brain and gray matter volumes when compared to HC. After a median follow-up time of 4.5 years, the ci-RIS subgroup presented a higher conversion rate to MS, suggesting that CI might be an independent risk factor for conversion to MS.

The cytosolic tryparedoxin peroxidase from Trypanosoma cruzi induces a pro-inflammatory Th1 immune response in a peroxidatic cysteine-dependent manner.

Trypanosoma cruzi cytosolic tryparedoxin peroxidase (c-TXNPx) is a 2-Cys peroxiredoxin (Prx) with an important role in detoxifying host cell oxidative molecules during parasite infection. c-TXNPx is a virulence factor, as its overexpression enhances parasite infectivity and resistance to exogenous oxidation. As Prxs from other organisms possess immunomodulatory properties, we studied the effects of c-TXNPx in the immune response and analysed whether the presence of the peroxidatic cysteine is necessary to mediate these properties. To this end, we used a recombinant c-TXNPx and a mutant version (c-TXNPxC52S) lacking the peroxidatic cysteine. We first analysed the oligomerization profile, oxidation state and peroxidase activity of both proteins by gel filtration, Western blot and enzymatic assay, respectively. To investigate their immunological properties, we analysed the phenotype and functional activity of macrophage and dendritic cells and the T-cell response by flow cytometry after injection into mice. Our results show that c-TXNPx, but not c-TXNPxC52S, induces the recruitment of IL-12/23p40-producing innate antigen-presenting cells and promotes a strong specific Th1 immune response. Finally, we studied the cellular and humoral immune response developed in the context of parasite natural infection and found that only wild-type c-TXNPx induces proliferation and high levels of IFN-γ secretion in PBMC from chronic patients without demonstrable cardiac manifestations. In conclusion, we demonstrate that c-TXNPx possesses pro-inflammatory properties that depend on the presence of peroxidatic cysteine that is essential for peroxidase activity and quaternary structure of the protein and could contribute to rational design of immune-based strategies against Chagas disease.

Plant density on yield of Husk tomato (Physalis ixocarpa Brot.) in field and greenhouse / Densidade vegetal no rendimento de tomate Husk (Physalis ixocarpa Brot.) em campo e casa de vegetação

ABSTRACT: Physalis ixocarpa Brot. (tomatillo or Husk tomato) is one of the five major vegetables cultivated in Mexico, but its yield in the field is low. However, greenhouse crops and the enhancement in plant density can promote an increase in yield per area. The aim of this research was to evaluate: yield, water consumption and water use efficiency of variety husk tomato 'Diamante'. The experiment was conducted under field and greenhouse conditions, during the two crop cycles (autumn-winter and spring-summer), with different planting densities (1.5, 2 and 3 plants m-2), in complete random blocks and three replications. The yield was influenced by the planting density and environments. In both environments, the planting density, with 3 plants m-2 increased yield 32 %, and 25% in water use efficiency (WUE). In greenhouse increased 32% yield m-2 and the WUE it was 18.1 kg m-3 while in the field was 16.4 kg m-3. Crop cycle spring-summer produced differences of 27% in plant length and 15% in stem diameter, probably due to the temperature that was 4 ºC higher with respect to autumn-winter.

RESUMO: Physalis ixocarpa Brot. (tomatillo ou tomate de cáscara) é um dos cinco principais vegetais cultivados no México, mas seu rendimento no campo é baixo. No entanto, as culturas em estufa e o aumento da densidade das plantas podem promover um aumento no rendimento por área. O objetivo desta pesquisa foi avaliar: rendimento, consumo de água e eficiência no uso da água do tomate de casca de variedade 'Diamante'. O experimento foi conduzido em condições de campo e casa de vegetação, durante os dois ciclos de cultivo (outono-inverno e primavera-verão), com diferentes densidades de plantio (1,5, 2 e 3 plantas m-2), em blocos aleatórios completos e três replicações. O rendimento foi influenciado pela densidade e pelos ambientes de plantio. Nos dois ambientes, a densidade de plantio, com três plantas m-2, aumentou a produtividade em 32% e em 25% na eficiência no uso da água (WUE). Em casa de vegetação aumentou 32% do rendimento m-2 e o WUE foi de 18,1 kg m-3, enquanto no campo foi de 16,4 kg m-3. O ciclo da safra primavera-verão produziu diferenças de 27% no comprimento das plantas e 15% no diâmetro do caule, provavelmente devido à temperatura 4 ºC maior em relação ao outono-inverno.

New Scheme of Intermittent Benznidazole Administration in Patients Chronically Infected with Trypanosoma cruzi: Clinical, Parasitological, and Serological Assessment after Three Years of Follow-Up.

In a pilot study, we showed that the intermittent administration of benznidazole in chronic Chagas disease patients resulted in a low rate of treatment suspension and therapeutic failure, as assessed by quantitative PCR (qPCR) at the end of treatment. Here, a 3-year posttreatment follow-up study of the same cohort of patients is presented. The treatment scheme consisted of 12 doses of benznidazole at 5 mg/kg of body weight/day in two daily doses every 5 days. Parasite load, Trypanosoma cruzi-specific antibodies, and serum chemokine levels were measured prior to treatment and after a median follow-up of 36 months posttreatment by DNA minicircle kinetoplastid and nuclear DNA satellite sequence qPCR methods, conventional serological techniques, a Luminex-based assay with recombinant T. cruzi proteins, and a cytometric bead array. At the end of follow-up, 14 of 17 (82%) patients had negative qPCR findings, whereas three of 17 (18%) had detectable nonquantifiable findings by at least one of the qPCR techniques. A decline in parasite-specific antibodies at 12 months posttreatment was confirmed by conventional serological tests and the Luminex assays. Monocyte chemoattractant protein 1 levels increased after treatment, whereas monokine induced by gamma interferon levels decreased. New posttreatment electrocardiographic abnormalities were observed in only one patient who had cardiomyopathy prior to treatment. Together, these data strengthen our previous findings by showing that the intermittent administration of benznidazole results in a low rate of treatment suspension, with treatment efficacy comparable to that of a daily dose of 5 mg/kg for 60 days.

Short-term effect of a synbiotic in salivary viscosity and buffering capacity; a quasi-experimental study / Efecto a corto plazo de un simbiótico en la viscosidad y la capacidad tampón salival; un estudio cuasi experimental

Evaluate the effect of a synbiotic on salivary viscosity and buffer capacity. Materials and Methods: A follow-up one-week study was performed on 24 healthy volunteers in San Luis Potosí, Mexico, during July 2017. Volunteers must have had active tooth decay at the moment of study. All 24 patients were given a Lactiv® probiotic package, advising not to modify usual oral hygiene practices, and were followed up during 6 days. Primary output variable was salivary viscosity while the secondary was salivary buffer capacity. Salivary viscosity was assessed by using an Ostwald Pipette and buffer capacity with bromocresol purple. Results: A total of 8 male patients (33.3%) and 16 females (66.6%) patients were included, with an average age of 10.92 years. All the volunteers completed the study. Comparisons between pre- and post-treatment showed a decrease in salivary viscosity, while buffer capacity was showed to increase. Conclusion: The use of a synbiotic during a short period of time lowered the viscosity of saliva and increased salivary buffer capacity.

Evaluar el efecto de un sinbiótico sobre la viscosidad salival y la capacidad de tampón de la saliva. Materiales and Métodos: Se realizó un estudio de seguimiento de una semana en 24 voluntarios sanos en San Luis Potosí, México, durante julio de 2017. Los voluntarios cursaban caries dental activa en el momento del estudio. Los 24 pacientes recibieron un paquete de probióticos Lactiv®, fueron aconsejados a no modificar las prácticas habituales de higiene oral, y fueron seguidos durante 6 días. La variable primaria fue la viscosidad salival mientras que la secundaria fue la capacidad tampón. La viscosidad salival se evaluó usando una pipeta Ostwald y capacidad tampón con bromocresol púrpura. Resultados: Se incluyeron un total de 8 pacientes varones (33,3%) y 16 mujeres (66,6%), con una edad promedio de 10,92 años. Todos los voluntarios completaron el estudio. Las comparaciones entre el pretratamiento y el postratamiento mostraron una disminución de la viscosidad salival, mientras que se demostró que la capacidad del tampón aumentó. Conclusión: El uso de un sinbiótico durante un corto período de tiempo mostró un efecto sobre la disminución de la viscosidad y el aumento de la capacidad del tampón salival.

In Silico Guided Discovery of Novel Class I and II Trypanosoma cruzi Epitopes Recognized by T Cells from Chagas' Disease Patients.

T cell-mediated immune response plays a crucial role in controlling Trypanosoma cruzi infection and parasite burden, but it is also involved in the clinical onset and progression of chronic Chagas' disease. Therefore, the study of T cells is central to the understanding of the immune response against the parasite and its implications for the infected organism. The complexity of the parasite-host interactions hampers the identification and characterization of T cell-activating epitopes. We approached this issue by combining in silico and in vitro methods to interrogate patients' T cells specificity. Fifty T. cruzi peptides predicted to bind a broad range of class I and II HLA molecules were selected for in vitro screening against PBMC samples from a cohort of chronic Chagas' disease patients, using IFN-γ secretion as a readout. Seven of these peptides were shown to activate this type of T cell response, and four out of these contain class I and II epitopes that, to our knowledge, are first described in this study. The remaining three contain sequences that had been previously demonstrated to induce CD8+ T cell response in Chagas' disease patients, or bind HLA-A*02:01, but are, in this study, demonstrated to engage CD4+ T cells. We also assessed the degree of differentiation of activated T cells and looked into the HLA variants that might restrict the recognition of these peptides in the context of human T. cruzi infection.

Seed and seedling quality of three chilis (Capsicum annuum L.) native to Oaxaca, Mexico / Qualidade de sementes e plântulas de três pimentas (Capsicum annuum L.) endêmicas de Oaxaca, México

ABSTRACT: The diversity of chilis in Oaxaca is one of the most extensive in Mexico. Growers select seeds in the traditional manner; information on its quality is unknown. The aim of this research was to compare the physical and physiological quality of seeds and seedlings of three native types to chili (Huacle, De agua and Pasilla) and of the commercial Green pepper as control. Fifteen variables were evaluated in seed and twelve in seedlings. The laboratory experiments were established under a completely randomized design. Means of the variables were compared using the Tukey test (α=0.05). Results showed that Pasilla chili had the highest values in seed size and weight, which was 1.44 g heavier than the control and 2.09 to 3.73 g higher than native types. Haucle chili and green pepper had a 90% germination rate, while chili De agua and Pasilla chili had germination rates of 51 and 38%, respectively. Huacle chili had the highest germination rate index (29.89) and seedling vigor index (992.25). The top highest values of number of normal seedlings were obtained in the control and Huacle chili seedlings (72 and 88%); also, the latter had the longest plumule (3.36 cm) and radicle (7.67 cm) values. Both Huacle and Pasilla chili seedlings had larger values in height, stem thickness, number of leaves, leaf area and slenderness index than De agua and Green pepper. Huacle chili had good physical and physiological quality similar to the seeds of the commercial Green pepper.

RESUMO: Oaxaca é umas das regiões de maior diversidade de espécies de pimentas do México. Os agricultores selecionam sementes da maneira tradicional; informações sobre sua qualidade são desconhecidas. O objetivo desta pesquisa foi comparar a qualidade física e fisiológica de sementes e mudas de três tipos nativos de pimenta (Huacle, De Agua e Pasilla) e pimenta verde comercial como controle. Quinze variáveis foram avaliadas em sementes e doze em mudas. As experiências de laboratório foram estabelecidas sob um delineamento inteiramente casualizado. As médias das variáveis foram comparadas pelo teste de Tukey (α=0.05). Os resultados mostraram que o Pasilla apresentou os maiores valores em tamanho e peso de sementes, 1,44 g mais pesado que o controle e 2,09 a 3,73 g maior que os demais tipos de pimenta nativa. A pimenta Huacle e a pimenta verde tiveram 90% de germinação de 90%, enquanto que De Agua e Pasilla foi de 51 e 38%, respectivamente. A pimienta Huacle apresentou os maiores índices de taxa de germinação (29,89) e de vigor de plântulas (992,25). Os maiores valores máximos no número de mudas normais foram obtidos no controle e na pimenta Huacle (72 e 88%). Além disso, este último apresentou os maiores valores de plúmula (3,36 cm) e radícula (7,67 cm). As mudas do Huacle e Pasilla apresentaram maiores valores em altura, espessura do caule, número de folhas, área foliar e índice de esbelto em relação à pimenta, De agua e ao controle. O Huacle apresentou boa qualidade física e fisiológica, semelhante às sementes da pimentão comercial.

Correction to: Nifurtimox versus benznidazole or placebo for asymptomatic Trypanosoma cruzi infection (Equivalence of Usual Interventions for Trypanosomiasis - EQUITY): study protocol for a randomised controlled trial.

Following publication of the original article [1], the authors notified us of a few requested editions that were not implemented adequately during proofing. The publisher apologizes for the inconvenience caused to our authors and readers.

Nifurtimox versus benznidazole or placebo for asymptomatic Trypanosoma cruzi infection (Equivalence of Usual Interventions for Trypanosomiasis - EQUITY): study protocol for a randomised controlled trial.

BACKGROUND: Either benznidazole (BZN) or nifurtimox (NFX) is recommended as equivalent to treat Trypanosoma cruzi infection. Nonetheless, supportive data from randomised trials is limited to individuals treated with BZN in southern cone countries of Latin America. METHODS: The goal of this randomised, concealed, blind, parallel-group trial is to inform the trypanocidal efficacy and safety of NFX and its equivalence to BZN among individuals with T. cruzi positive serology (TC+). Eligible individuals are TC+, 20-65 years old, with no apparent symptoms/signs or uncontrolled risk factors for cardiomyopathy and at negligible risk of re-infection. Consenting individuals (adherent to a 10-day placebo run-in phase) receive a 120-day BID blinded treatment with NFX, BZN or matching placebo (2:2:1 ratio). The four active medication arms include (1) a randomly allocated sequence of 60-day, conventional-dose (60CD) regimes (BZN 300 mg/day or NFX 480 mg/day, ratio 1:1), followed or preceded by a 60-day placebo treatment, or (2) 120-day half-dose (120HD) regimes (BZN 150 mg/day or NFX 240 mg/day, ratio 1:1). The primary efficacy outcome is the proportion of participants testing positive at least once for up to three polymerase chain reaction (PCR) assays (1 + PCR) 12-18 months after randomisation. A composite safety outcome includes moderate to severe adverse reactions, consistent blood marker abnormalities or treatment abandons. The trial outside Colombia (expected to recruit at least 60% of participants) is pragmatic; it may be open-label and not include all treatment groups, but it must adhere to the randomisation and data administration system and guarantee a blinded efficacy outcome evaluation. Our main comparisons include NFX groups with placebo (for superiority), NFX versus BZN groups and 60CD versus 120HD groups (for non-inferiority) and testing for the agent-dose and group-region interactions. Assuming a 1 + PCR ≥ 75% in the placebo group, up to 25% among BZN-treated and an absolute difference of up to ≥ 25% with NFX to claim its trypanocidal effect, 60-80 participants per group (at least 300 from Colombia) are needed to test our hypotheses (80-90% power; one-sided alpha level 1%). DISCUSSION: The EQUITY trial will inform the trypanocidal effect and equivalence of nitroderivative agents NFX and BZN, particularly outside southern cone countries. Its results may challenge current recommendations and inform choices for these agents. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02369978 . Registered on 24 February 2015.

Survival of Entomopathogenic Nematodes in Oil Emulsions and Control Effectiveness on Adult Engorged Ticks (Acari: Ixodida).

Although their control is based on chemical products, the infestations by ticks (Ixodes scapularis Say) are causing great losses and damages in the livestock production worldwide. In this study, the survival of the entomopathogenic nematodes Heterorhabditis bacteriophora, Steinernema carpocapsae and Steinernema websteri in vegetal oil suspension at concentrations of 13% and 33% and their effectiveness to control ticks at concentrations of 50 ± 5 and 100 ± 10 nematodes in oil suspensions of Cymbopogon citratus, Pelargonium sp, Juniperus virginiana, Rosa sp, and Mentha piperita were evaluated in lab conditions. In field conditions, the Lethal Concentration (LC90) of S. websteri in oil suspensions of J. virginiana and C. citratus in dogs infested with ticks was evaluated. In the laboratory, it was found that an oil emulsion of C. citratus and J. virginiana at 13% maintained the survival of S. carpocapsae, H. bacteriophora and S. websteri from 55% to 60% for a period of 96 hr. The combination of the S. websteri nematode with 50 or 100 nematodes in oil emulsions of J. virginiana at 33% presented a control effectiveness of 80-100% in adult ticks 24 hr post-application. In field, the LC90 of 119 juveniles of S. websteri in oil emulsions of J. virginiana at 33% on domestic dogs presented an accumulated a control effectiveness of 89% after 96 hr post-application. The combined application of J. virginiana and S. websteri could be a good alternative for the control of ticks. It was observed that the time of contact and the type of vegetable oil were crucial factors to increase the effectiveness of control.Although their control is based on chemical products, the infestations by ticks (Ixodes scapularis Say) are causing great losses and damages in the livestock production worldwide. In this study, the survival of the entomopathogenic nematodes Heterorhabditis bacteriophora, Steinernema carpocapsae and Steinernema websteri in vegetal oil suspension at concentrations of 13% and 33% and their effectiveness to control ticks at concentrations of 50 ± 5 and 100 ± 10 nematodes in oil suspensions of Cymbopogon citratus, Pelargonium sp, Juniperus virginiana, Rosa sp, and Mentha piperita were evaluated in lab conditions. In field conditions, the Lethal Concentration (LC90) of S. websteri in oil suspensions of J. virginiana and C. citratus in dogs infested with ticks was evaluated. In the laboratory, it was found that an oil emulsion of C. citratus and J. virginiana at 13% maintained the survival of S. carpocapsae, H. bacteriophora and S. websteri from 55% to 60% for a period of 96 hr. The combination of the S. websteri nematode with 50 or 100 nematodes in oil emulsions of J. virginiana at 33% presented a control effectiveness of 80­100% in adult ticks 24 hr post-application. In field, the LC90 of 119 juveniles of S. websteri in oil emulsions of J. virginiana at 33% on domestic dogs presented an accumulated a control effectiveness of 89% after 96 hr post-application. The combined application of J. virginiana and S. websteri could be a good alternative for the control of ticks. It was observed that the time of contact and the type of vegetable oil were crucial factors to increase the effectiveness of control.

Digoxin and prognosis of heart failure in older patients with preserved ejection fraction: Importance of heart rate. Results from an observational and multicenter study.

BACKGROUND: The value of digoxin in heart failure (HF) remains controversial, particularly in patients with preserved ejection fraction (HFpEF). This study evaluated the 1-year risk of events after digoxin treatment for acute heart failure (AHF) in patients >70 years old with HFpEF. METHODS: 1833 patients were included in this analysis (mean age, 82 years). The main endpoints were all-cause death and the composite of death and/or HF re-admission within 1 year. Cox regression analysis was used to evaluate the association between digoxin treatment and prognosis. RESULTS: 401 patients received digoxin treatment; of these, 86% had atrial fibrillation. The mean baseline heart rate was 86 ±â€¯22 bpm. At the 1-year follow-up, 375 patients (20.5%) died and 684 (37.3%) presented composite endpoints. Patients treated with digoxin showed higher rates of death (3.21 vs. 2.44 per 10 person-years, p = .019) and composite endpoint (6.72 vs. 5.18 per 10 person-years, p = .003). After multivariate adjustment, digoxin treatment remained associated with increased risks of death (HR = 1.46, 95% CI: 1.16-1.85, p = .001) and the composite endpoint (HR = 1.35, 95% CI: 1.13-1.61, p = .001). A distinctive prognostic effect of digoxin was found across the heart rate continuum; the risks for both endpoints were higher at lower heart rates and neutral at higher heart rates (p of the interactions = 0.007 and 0.03, respectively). CONCLUSIONS: In older patients with HFpEF discharged after AHF, digoxin treatment was associated with increased mortality and/or re-admission, particularly in patients with lower heart rates.