Effects induced by Apis mellifera venom and its components in experimental models of nociceptive and inflammatory pain

AbstractThe effects induced by Apis mellifera venom (AMV), melittin-free AMV, fraction with molecular mass < 10 kDa (F<10) or melittin in nociceptive and inflammatory pain models in mice were investigated. Subcutaneous administration of AMV (2, 4 or 6 mg/kg) or melittin-free AMV (1, 2 or 4 mg/kg) into the dorsum of mice inhibited both phases of formaldehyde-induced nociception. However, F<10 (2, 4 or 6 mg/kg) or melittin (2 or 3 mg/kg) inhibited only the second phase. AMV (4 or 6 mg/kg), but not F<10, melittin-free AMV or melittin, induced antinociception in the hot-plate model. Paw injection of AMV (0.05 or 0.10 mg), F<10 (0.05 or 0.1 mg) or melittin (0.025 or 0.050 mg) induced a nociceptive response. In spite of inducing nociception after paw injection, scorpion (Tityus serrulatus) or snake (Bothrops jararaca) venom injected into the dorsum of mice did not inhibit formaldehyde-induced nociception. In addition, AMV (6 mg/kg), but not F<10 (6 mg/kg) or melittin (3 mg/kg), inhibited formaldehyde paw oedema. Concluding, AMV, F<10 and melittin induce two contrasting effects: nociception and antinociception. AMV antinociception involves the action of different components and does not result from non-specific activation of endogenous antinociceptive mechanisms activated by exposure to noxious stimuli

Nicotinic acid induces antinociceptive and anti-inflammatory effects in different experimental models

AbstractAlthough in vitro studies have shown that nicotinic acid inhibits some aspects of the inflammatory response, a reduced number of in vivo studies have investigated this activity. To the best of our knowledge, the effects induced by nicotinic acid in models of nociceptive and inflammatory pain are not known. Per os (p.o.) administration of nicotinic acid (250, 500 or 1000mg/kg, −1h) inhibited the first and the second phases of the nociceptive response induced by formalin in mice. Nicotinic acid (250 or 500mg/kg, −1 and 3h) also inhibited the mechanical allodynia induced by carrageenan in rats, a model of inflammatory pain. However, in a model of nociceptive pain, exposure of mice to a hot-plate, nicotinic acid was devoid of activity. In addition to inhibiting the nociceptive response in models of inflammatory pain, nicotinic acid (250 or 500mg/kg, p.o., −1 and 3h) inhibited paw edema induced by carrageenan in mice and rats. Picolinic acid (62.5 or 125mg/kg, p.o., −1h), a nicotinic acid isomer, inhibited both phases of the nociceptive response induced by formalin, but not paw edema induced by carrageenan in mice. The other nicotinic acid isomer, isonicotinic acid, was devoid of activity in these two models. In conclusion, our results represent the first demonstration of the activity of nicotinic acid in experimental models of nociceptive and inflammatory pain and also provide further support to its anti-inflammatory activity. It is unlikely that conversion to nicotinamide represents an important mechanism to explain the antinociceptive and anti-inflammatory activities of nicotinic acid. The demonstration of new activities of nicotinic acid, a drug that has already been approved for clinical use and presents a positive safety record, may contribute to raise the interest in conducting clinical trials to investigate its usefulness in the treatment of painful and inflammatory diseases

The cost-effectiveness of controlling dengue in Indonesia using wMel Wolbachia released at scale: a modelling study.

BACKGROUND: Release of virus-blocking Wolbachia-infected mosquitoes is an emerging disease control strategy that aims to control dengue and other arboviral infections. Early entomological data and modelling analyses have suggested promising outcomes, and wMel Wolbachia releases are now ongoing or planned in 12 countries. To help inform government, donor, or philanthropist decisions on scale-up beyond single city releases, we assessed this technology's cost-effectiveness under alternative programmatic options. METHODS: Using costing data from existing Wolbachia releases, previous dynamic model-based estimates of Wolbachia effectiveness, and a spatially explicit model of release and surveillance requirements, we predicted the costs and effectiveness of the ongoing programme in Yogyakarta City and three new hypothetical programmes in Yogyakarta Special Autonomous Region, Jakarta, and Bali. RESULTS: We predicted Wolbachia to be a highly cost-effective intervention when deployed in high-density urban areas with gross cost-effectiveness below $1500 per DALY averted. When offsets from the health system and societal perspective were included, such programmes even became cost saving over 10-year time horizons with favourable benefit-cost ratios of 1.35 to 3.40. Sequencing Wolbachia releases over 10 years could reduce programme costs by approximately 38% compared to simultaneous releases everywhere, but also delays the benefits. Even if unexpected challenges occurred during deployment, such as emergence of resistance in the medium-term or low effective coverage, Wolbachia would remain a cost-saving intervention. CONCLUSIONS: Wolbachia releases in high-density urban areas are expected to be highly cost-effective and could potentially be the first cost-saving intervention for dengue. Sites with strong public health infrastructure, fiscal capacity, and community support should be prioritised

Pathophysiological Mechanisms In Gaseous Therapies For Severe Malaria.

Over 200 million people worldwide suffer from malaria every year, a disease that causes 584,000 deaths annually. In recent years, significant improvements have been achieved on the treatment of severe malaria, with intravenous artesunate proving superior to quinine. However, mortality remains high at 8% in children and 15% in adults in clinical trials, and even worse in the case of cerebral malaria (18% and 30%, respectively). Moreover, some individuals who do not succumb to severe malaria present long-term cognitive deficits. These observations indicate that strategies focused only on parasite killing fail to prevent neurological complications and deaths associated with severe malaria, possibly because clinical complications are associated in part with a cerebrovascular dysfunction. Consequently, different adjunctive therapies aimed at modulating malaria pathophysiological processes are currently being tested. However, none of these therapies has shown unequivocal evidence in improving patients' clinical status. Recently, key studies have shown that gaseous therapies based mainly on nitric oxide (NO), carbon monoxide (CO) and hyperbaric (pressurized) oxygen (HBO) alter vascular endothelium dysfunction and modulate host immune response to infection. Considering gaseous administration as a promising adjunctive treatment against severe malaria cases, we review here the pathophysiological mechanisms and the immunological aspects of such therapies.8

Alfalfa water productivity and yield gaps in the U.S. central Great Plains

Context: Yield gap (Yg) analyses using farmer-reported yield and management data have been performed for a number of annual grain crops, but it lacks for perennial forages. The U.S. accounts for 21 % of the global alfalfa production with a large rainfed area located in the central Great Plains, serving as an interesting case-study for Yg in perennial forages. Most existing alfalfa Yg analyses quantified the magnitude of the Yg but failed to identify associated management practices to reduce it. Challenging this analysis, a systematic benchmark for alfalfa water productivity [WP, kg dry matter per mm evapotranspiration (ETc)] that allows for the quantification of Yg in farmer fields does not exist. Objectives: Our objectives were to (i) benchmark alfalfa WP, (ii) quantify Yg in alfalfa farmer fields, and (iii) identify management opportunities to improve alfalfa yield. Methods: We conducted a systematic review of literature and compiled a database on alfalfa yield and ETc (n = 68 papers and 1027 treatment means) from which a WP boundary function was derived. We collected management and yield data from 394 commercial rainfed alfalfa fields during 2016–2019 in central Kansas. We then used satellite imagery to define the growing season (and corresponding water supply) for each field. The boundary function was then used to calculate Yg of each field, and conditional inference trees (CIT) explored the impact of management practices associated with increased yield. Results: Our boundary function suggested an alfalfa WP of 34 kg ha-1 mm-1. Farmer-reported yield ranged from 0.9 to 19.0 Mg ha-1, averaging 7.6 Mg ha-1. Alfalfa water-limited yield potential (Yw) ranged from 11.1 to 23.2 Mg ha-1, resulting in an average yield gap of 54–60 % of Yw. Row spacing, seeding rates, and management of phosphorus fertilizer were major agronomic practices explaining alfalfa yields in farmer fields, followed by surrogate variables as sowing season, stand age, and soil pH. Conclusions: Our study provided the first systematic analysis estimating attainable alfalfa WP as function of ETc, suggesting that large alfalfa Yg exist in the U.S. central Great Plains. We also identified key agronomic practices associated with increased alfalfa yield. Significance: The WP here derived can be used for future studies aiming at quantifying alfalfa Yg across the globe. This was an initial step in quantifying Yg and its associated causes at farmer fields, and we highlight limitations and future directions for perennial forages yield gap analyses

Early-season plant-to-plant spatial uniformity can affect soybean yields

Increased soybean (Glycine max L. Merril) seed costs have motivated interest in reduced seeding rates to improve profitability while maintaining or increasing yield. However, little is known about the effect of early-season plant-to-plant spatial uniformity on the yield of modern soybean varieties planted at reduced seeding rates. The objectives of this study were to (i) investigate traditional and devise new metrics for characterizing early-season plant-to-plant spatial uniformity, (ii) identify the best metrics correlating plant-to-plant spatial uniformity and soybean yield, and (iii) evaluate those metrics at different seeding rate (and achieved plant density) levels and yield environments. Soybean trials planted in 2019 and 2020 compared seeding rates of 160, 215, 270, and 321 thousand seeds ha−1 planted with two different planters, Max Emerge and Exact Emerge, in rainfed and irrigated conditions in the United States (US). In addition, trials comparing seeding rates of 100, 230, 360, and 550 thousand seeds ha−1 were conducted in Argentina (Arg) in 2019 and 2020. Achieved plant density, grain yield, and early-season plant-to-plant spacing (and calculated metrics) were measured in all trials. All site-years were separated into low- (2.7 Mg ha−1), medium- (3 Mg ha−1), and high- (4.3 Mg ha−1) yielding environments, and the tested seeding rates were separated into low ( 300 seeds m−2) levels. Out of the 13 metrics of spatial uniformity, standard deviation (sd) of spacing and of achieved versus targeted evenness index (herein termed as ATEI, observed to theoretical ratio of plant spacing) showed the greatest correlation with soybean yield in US trials (R2 = 0.26 and 0.32, respectively). However, only the ATEI sd, with increases denoting less uniform spacing, exhibited a consistent relationship with yield in both US and Arg trials. The effect of spatial uniformity (ATEI sd) on soybean yield differed by yield environment. Increases in ATEI sd (values > 1) negatively impacted soybean yields in both low- and medium-yield environments, and in achieved plant densities below 200 thousand plants ha−1. High-yielding environments were unaffected by variations in spatial uniformity and plant density levels. Our study provides new insights into the effect of early-season plant-to-plant spatial uniformity on soybean yields, as influenced by yield environments and reduced plant densities.Fil: Pereyra, Valentina M.. Kansas State University; Estados UnidosFil: Bastos, Leonardo M.. University of Georgia; Estados UnidosFil: Froes de Borja Reis, André. State University of Louisiana; Estados UnidosFil: Melchiori, Ricardo J. M.. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Entre Ríos. Estación Experimental Agropecuaria Paraná; ArgentinaFil: Maltese, Nicolás Elías. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Entre Ríos. Facultad de Ciencias Agropecuarias; ArgentinaFil: Appelhans, Stefania Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Entre Ríos. Facultad de Ciencias Agropecuarias; ArgentinaFil: Vara Prasad, P. V.. Kansas State University; Estados UnidosFil: Wright, Yancy. No especifíca;Fil: Brokesh, Edwin. Kansas State University; Estados UnidosFil: Sharda, Ajay. Kansas State University; Estados UnidosFil: Ciampitti, Ignacio Antonio. Kansas State University; Estados Unido

Soybean yield does not rely on mineral fertilizer in rotation with flooded rice under a no-till integrated crop-livestock system

In subtropical lowlands, the introduction of soybean and livestock in rotation are an alternative to rice monoculture. Due to the nutrient cycling process improved by animal grazing in winter fertilized pastures, soybean may not respond to mineral fertilization under a no-till integrated crop–livestock system (ICLS). Thus, the objectives of this study were to evaluate (i) the soybean yield response to different fertilization levels of phosphorus (P) and potassium (K) and (ii) the relationship between soybean yield and soil chemical properties sampled in different soil layers, in a no-till ICLS in subtropical lowlands. Two field studies were conducted in a system that included a soybean-flooded rice rotation integrated with cattle grazing during the winter season. During the 2015/2016 cropping season, five levels of P and K fertilization were applied to the soil. During the 2017/2018 cropping season, the relationships between soybean yield and soil chemical properties were evaluated under no fertilization treatment. Soybean yield under an ICLS did not respond to P and K fertilization, even when the soil P level was below the critical threshold. The associations between soybean yield and soil chemical properties were greatest in the 10–20 cm soil layer as compared with the 0–10 cm soil layer, especially for available P, followed by pH and soil organic matter (SOM). The crop rotation and ICLS adoption under no-till reduced the soybean reliance for mineral fertilization prior to cropping. Results of this study inform producers of possible fertilization adjustments, in which supplementing mineral fertilizer for soybean may not be necessary

Winter Wheat Yield Response to Plant Density as a Function of Yield Environment and Tillering Potential: A Review and Field Studies

Wheat (Triticum aestivum L.) grain yield response to plant density is inconsistent, and the mechanisms driving this response are unclear. A better understanding of the factors governing this relationship could improve plant density recommendations according to specific environmental and genetics characteristics. Therefore, the aims of this paper were to: i) execute a synthesis-analysis of existing literature related to yield-plant density relationship to provide an indication of the need for different agronomic optimum plant density (AOPD) in different yield environments (YEs), and ii) explore a data set of field research studies conducted in Kansas (USA) on yield response to plant density to determine the AOPD at different YEs, evaluate the effect of tillering potential (TP) on the AOPD, and explain changes in AOPD via variations in wheat yield components. Major findings of this study are: i) the synthesis-analysis portrayed new insights of differences in AOPD at varying YEs, reducing the AOPD as the attainable yield increases (with AOPD moving from 397 pl m-2 for the low YE to 191 pl m-2 for the high YE); ii) the field dataset confirmed the trend observed in the synthesis-analysis but expanded on the physiological mechanisms underpinning the yield response to plant density for wheat, mainly highlighting the following points: a) high TP reduces the AOPD mainly in high and low YEs, b) at canopy-scale, both final number of heads and kernels per square meter were the main factors improving yield response to plant density under high TP, c) under varying YEs, at per-plant-scale, a compensation between heads per plant and kernels per head was the main factor contributing to yield with different TP.Fil: Bastos, Leonardo M.. Kansas State University; Estados UnidosFil: Carciochi, Walter Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Kansas State University; Estados UnidosFil: Lollato, Romulo P.. Kansas State University; Estados UnidosFil: Jaenisch, Brent R.. Kansas State University; Estados UnidosFil: Rezende, Caio R.. Kansas State University; Estados UnidosFil: Schwalbert, Rai. Kansas State University; Estados UnidosFil: Vara Prasad, P.V.. Kansas State University; Estados UnidosFil: Zhang, Guorong. Kansas State University; Estados UnidosFil: Fritz, Allan K.. Kansas State University; Estados UnidosFil: Foster, Chris. John Deer; Estados UnidosFil: Wright, Yancy. John Deer; Estados UnidosFil: Young, Steven. John Deer; Estados UnidosFil: Bradley, Pauley. John Deer; Estados UnidosFil: Ciampitti, Ignacio Antonio. Kansas State University; Estados Unido