Nociplastic pain mechanisms and toll-like receptors as promising targets for its management.

ABSTRACT: Nociplastic pain, characterized by abnormal pain processing without an identifiable organic cause, affects a significant portion of the global population. Unfortunately, current pharmacological treatments for this condition often prove ineffective, prompting the need to explore new potential targets for inducing analgesic effects in patients with nociplastic pain. In this context, toll-like receptors (TLRs), known for their role in the immune response to infections, represent promising opportunities for pharmacological intervention because they play a relevant role in both the development and maintenance of pain. Although TLRs have been extensively studied in neuropathic and inflammatory pain, their specific contributions to nociplastic pain remain less clear, demanding further investigation. This review consolidates current evidence on the connection between TLRs and nociplastic pain, with a specific focus on prevalent conditions like fibromyalgia, stress-induced pain, sleep deprivation-related pain, and irritable bowel syndrome. In addition, we explore the association between nociplastic pain and psychiatric comorbidities, proposing that modulating TLRs can potentially alleviate both pain syndromes and related psychiatric disorders. Finally, we discuss the potential sex differences in TLR signaling, considering the higher prevalence of nociplastic pain among women. Altogether, this review aims to shed light on nociplastic pain, its underlying mechanisms, and its intriguing relationship with TLR signaling pathways, ultimately framing the potential therapeutic role of TLRs in addressing this challenging condition.

Estradiol modulates the role of the spinal α6-subunit containing GABAA receptors in female rats with neuropathic pain.

The purpose of this study was to investigate the mechanisms underlying sex differences in the role of spinal α6-subunit containing GABAA (α6GABAA) receptors in rats with neuropathic pain. Intrathecal 2,5-dihydro-7-methoxy-2-(4-methoxyphenyl)-3H-pyrazolo [4,3-c] quinoline-3-one (PZ-II-029, positive allosteric modulator of α6GABAA receptors) reduced tactile allodynia in female but not in male rats with neuropathic pain. PZ-II-029 was also more effective in females than males in inflammatory and nociplastic pain. Ovariectomy abated the antiallodynic effect of PZ-II-029 in neuropathic rats, whereas 17ß-estradiol or 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT), estradiol receptor-α agonist, restored the effect of PZ-II-029 in ovariectomized rats. Blockade of estradiol receptor-α, using MPP (1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy) phenol]-1H-pyrazole dihydrochloride), prevented the effect of 17ß-estradiol on PZ-II-029-induced antiallodynia in ovariectomized neuropathic females. Nerve injury reduced α6GABAA receptor protein expression at the dorsal root ganglia (DRG) and spinal cord of intact and ovariectomized female rats. In this last group, reconstitution with 17ß-estradiol fully restored its expression in DRG and spinal cord. In male rats, nerve injury reduced α6GABAA receptor protein expression only at the spinal cord. Nerve injury enhanced estradiol receptor-α protein expression at the DRG in intact non-ovariectomized rats. However, ovariectomy decreased estradiol receptor-α protein expression at the DRG. In the spinal cord there were no changes in estradiol receptor-α protein expression. 17ß-estradiol restored estradiol receptor-α protein expression at the DRG and increased it at the spinal cord of neuropathic rats. These data suggest that 17ß-estradiol modulates the expression and function of the α6GABAA receptor through its interaction with estradiol receptor-α in female rats.

Broad immunogenic spectrum of monovalent and trivalent foot-and-mouth disease virus vaccines containing O1 campos, A24 cruzeiro and A Argentina 2001 strains against circulating viral lineages in cattle and pigs.

FMD remains endemic in many Asian and African countries where multiple variants of serotypes O and A, among others, currently circulate. Due to lack of cross-protection between serotypes and incomplete protection between some strains even within a serotype, an important challenge for the application of effective vaccination programs is to select highly immunogenic and widely cross-reactive vaccine strains. Adaptation of a candidate field virus for use as a vaccine can be quite complex, so that whenever possible, the use of well-established vaccine viruses could have enormous advantages. FMD vaccine strains harmonized for use in South America have shown excellent results in FMD control, not only in the region, where it is still used systematically as a preventive measure, but also more recently in some Asian countries. To gain further insight into the immunogenic spectrum of these strains, VN tests (VNT) were performed with sera from cattle and/or pigs vaccinated with monovalent (type O) or trivalent (types O and A) formulations against 122 type O and 32 type A field viruses isolated from 35 countries in Asia and Africa, belonging to different lineages. Almost all VNT titers obtained were within the expected protective level, indicating the wide immunogenic spectrum of high potency FMD vaccines formulated with O1 Campos, A24 Cruzeiro and A Argentina 2001 South American vaccine strains belonging to EURO-SA topotypes against currently active viruses from other topotypes. These in vitro results are in line with previously reported in vivo challenge tests in pigs against three A/ASIA/Sea-97 isolates and two isolates belonging to type O lineages O/SEA/Mya-98 and O/ME-SA/Ind-2001e.

Phenotypic variation in leaf photosynthetic traits, leaf area index, and carbon discrimination of field-grown wheat genotypes and their relationship with yield performance in Mediterranean environments.

MAIN CONCLUSION: Leaf water potential, gas exchange, and chlorophyll fluorescence exhibited significant differences among genotypes, high environmental effects, but low heritability. The highest-yielding and drought-tolerant genotypes presented superior harvest index and grain weight, compared to drought-susceptible ones. Physiological phenotyping can help identify useful traits related to crop performance under water-limited conditions. A set of fourteen bread wheat genotypes with contrasting grain yield (GY) was studied in eight Mediterranean environments in Chile, resulting from the combination of two sites (Cauquenes and Santa Rosa), two water conditions (rainfed-WL and irrigated-WW), and four growing seasons (2015-2018). The objectives were to (i) evaluate the phenotypic variation of leaf photosynthetic traits after heading (anthesis and grain filling) in different environments; (ii) analyze the relationship between GY and leaf photosynthetic traits and carbon isotope discrimination (Δ13C); and (iii) identify those traits that could have a greater impact in the determination of tolerant genotypes under field conditions. Agronomic traits exhibited significant genotypic differences and genotype × environment (GxE) interaction. The average GY under the WW condition at Santa Rosa was 9.2 Mg ha-1 (range 8.2-9.9 Mg ha-1) and under the WL condition at Cauquenes was 6.2 Mg ha-1 (range 3.7-8.3 Mg ha-1). The GY was closely related to the harvest index (HI) in 14 out of 16 environments, a trait exhibiting a relatively high heritability. In general terms, the leaf photosynthetic traits presented low GxE interaction, but high environmental effects and low heritability, except for the chlorophyll content. The relationships between GY and leaf photosynthetic traits were weaker when performed across genotypes in each environment, indicating low genotypic effects, and stronger when performed across environments for each genotype. The leaf area index and Δ13C also presented high environmental effects and low heritability, and their correlations with GY were influenced by environmental effects. The highest-yielding and drought-tolerant genotypes presented superior HI and grain weight, but no clear differences in leaf photosynthetic traits or Δ13C, compared to drought-susceptible ones. It seems that the phenotypic plasticity of agronomic and leaf photosynthetic traits is very important for crop adaptation to Mediterranean environments.

Activation of α 6 -containing GABA A receptors induces antinociception under physiological and pathological conditions.

ABSTRACT: The loss of GABAergic inhibition is a mechanism that underlies neuropathic pain. Therefore, rescuing the GABAergic inhibitory tone through the activation of GABA A receptors is a strategy to reduce neuropathic pain. This study was designed to elucidate the function of the spinal α 6 -containing GABA A receptor in physiological conditions and neuropathic pain in female and male rats. Results show that α 6 -containing GABA A receptor blockade or transient α 6 -containing GABA A receptor knockdown induces evoked hypersensitivity and spontaneous pain in naive female rats. The α 6 subunit is expressed in IB4 + and CGRP + primary afferent neurons in the rat spinal dorsal horn and dorsal root ganglia but not astrocytes. Nerve injury reduces α 6 subunit protein expression in the central terminals of the primary afferent neurons and dorsal root ganglia, whereas intrathecal administration of positive allosteric modulators of the α 6 -containing GABA A receptor reduces tactile allodynia and spontaneous nociceptive behaviors in female, but not male, neuropathic rats and mice. Overexpression of the spinal α 6 subunit reduces tactile allodynia and restores α 6 subunit expression in neuropathic rats. Positive allosteric modulators of the α 6 -containing GABA A receptor induces a greater antiallodynic effect in female rats and mice compared with male rats and mice. Finally, α 6 subunit is expressed in humans. This receptor is found in CGRP + and P2X3 + primary afferent fibers but not astrocytes in the human spinal dorsal horn. Our results suggest that the spinal α 6 -containing GABA A receptor has a sex-specific antinociceptive role in neuropathic pain, suggesting that this receptor may represent an interesting target to develop a novel treatment for neuropathic pain.

Exploring plant responses to abiotic stress by contrasting spectral signature changes.

In this study, daily changes over a short period and diurnal progression of spectral reflectance at the leaf level were used to identify spring wheat genotypes (Triticum aestivum L.) susceptible to adverse conditions. Four genotypes were grown in pots experiments under semi-controlled conditions in Chile and Spain. Three treatments were applied: i) control (C), ii) water stress (WS), and iii) combined water and heat shock (WS+T). Spectral reflectance, gas exchange and chlorophyll fluorescence measurements were performed on flag leaves for three consecutive days at anthesis. High canopy temperature ( H CT ) genotypes showed less variability in their mean spectral reflectance signature and chlorophyll fluorescence, which was related to weaker responses to environmental fluctuations. While low canopy temperature ( L CT ) genotypes showed greater variability. The genotypes spectral signature changes, in accordance with environmental fluctuation, were associated with variations in their stomatal conductance under both stress conditions (WS and WS+T); L CT genotypes showed an anisohydric response compared that of H CT , which was isohydric. This approach could be used in breeding programs for screening a large number of genotypes through proximal or remote sensing tools and be a novel but simple way to identify groups of genotypes with contrasting performances.

Arrhythmogenic and antiarrhythmic actions of late sustained sodium current in the adult human heart.

Late sodium current (late INa) inhibition has been proposed to suppress the incidence of arrhythmias generated by pathological states or induced by drugs. However, the role of late INa in the human heart is still poorly understood. We therefore investigated the role of this conductance in arrhythmias using adult primary cardiomyocytes and tissues from donor hearts. Potentiation of late INa with ATX-II (anemonia sulcata toxin II) and E-4031 (selective blocker of the hERG channel) slowed the kinetics of action potential repolarization, impaired Ca2+ homeostasis, increased contractility, and increased the manifestation of arrhythmia markers. These effects could be reversed by late INa inhibitors, ranolazine and GS-967. We also report that atrial tissues from donor hearts affected by atrial fibrillation exhibit arrhythmia markers in the absence of drug treatment and inhibition of late INa with GS-967 leads to a significant reduction in arrhythmic behaviour. These findings reveal a critical role for the late INa in cardiac arrhythmias and suggest that inhibition of this conductance could provide an effective therapeutic strategy. Finally, this study highlights the utility of human ex-vivo heart models for advancing cardiac translational sciences.

Genetic Yield Gains and Changes in Morphophysiological-Related Traits of Winter Wheat in Southern Chilean High-Yielding Environments.

Both the temperate-humid zone and the southern part of the Mediterranean climate region of Chile are characterized by high wheat productivity. Study objectives were to analyze the yield potential, yield progress, and genetic progress of the winter bread wheat (Triticum aestivum L.) cultivars and changes in agronomic and morphophysiological traits during the past 60 years. Thus, two field experiments: (a) yield potential and (b) yield genetic progress trials were conducted in high-yielding environments of central-southern Chile during the 2018/2019 and 2019/2020 seasons. In addition, yield progress was analyzed using yield historical data of a high-yielding environment from 1957 to 2017. Potential yield trials showed that, at the most favorable sites, grain yield reached ∼20.46 Mg ha-1. The prolonged growing and grain filling period, mild temperatures in December-January, ample water availability, and favorable soil conditions explain this high-potential yield. Yield progress analysis indicated that average grain yield increased from 2.70 Mg ha-1 in 1959 to 12.90 Mg ha-1 in 2017, with a 128.8 kg ha-1 per-year increase due to favorable soil and climatic conditions. For genetic progress trials, genetic gain in grain yield from 1965 to 2019 was 70.20 kg ha-1 (0.49%) per year, representing around 55% of the yield progress. Results revealed that the genetic gains in grain yield were related to increases in biomass partitioning toward reproductive organs, without significant increases in Shoot DW production. In addition, reducing trends in the NDVI, the fraction of intercepted PAR, the intercepted PAR (form emergence to heading), and the RGB-derived vegetation indices with the year of cultivar release were detected. These decreases could be due to the erectophile leaf habit, which enhanced photosynthetic activity, and thus grain yield increased. Also, senescence of bottom canopy leaves (starting from booting) could be involved by decreasing the ability of spectral and RGB-derived vegetation indices to capture the characteristics of green biomass after the booting stage. Contrary, a positive correlation was detected for intercepted PAR from heading to maturity, which could be due to a stay-green mechanism, supported by the trend of positive correlations of Chlorophyll content with the year of cultivar release.

Changes in the physiological and biochemical state of peanut plants (Arachis hypogaea L.) induced by exposure to green metallic nanoparticles.

Different types of nanoparticles (NPs) are increasingly used in multiple sectors such as industry, medicine and agriculture. This application has increased the possibility of NPs accumulating and contaminating the environment. Plants are one of the essential building blocks of all ecosystems and the interaction between NPs and plants is an indispensable aspect of risk assessment. To understand the effects of NPs in agricultural systems, in the present study we investigated the effects of exposure of Ag, Cu and Cu/Ag phytonanoparticles in Arachis hypogaea L. plants at a physiological and biochemical level, for which NPs solutions were applied foliarly at concentrations of 250, 500, 750 and 1000 ppm for 48 days. Parameters such as leaf length, chlorophyll and concentration of phytohormones showed that phytonanoparticles could cause serious damage to plant growth and development. Plants exposed to phytonanoparticles showed an increase in total phenols, proline, PAL activity and antioxidant enzymes, this to mitigate the stress caused. The alteration in the composition and content of fatty acids in the peanut kernels after exposure to different NPs indicated that they could affect the yield and quality of crop. Therefore, it is necessary to investigate its potential impact on food quality. Statement of noveltyIn this manuscript, we report for the first time that green nanoparticles induced a lower degree of toxicity in plants compared to commercial nanoparticles.Our results indicate that the mechanisms by which peanut plants respond to the application of nanoparticles were an increase in the activity of phenylalanine ammonia-lyase and antioxidant enzymes. So far there are few studies on the effect of nanoparticles on plant hormones, our results revealed a significant decrease in indole-3 acetic acid and induced the synthesis of gibberellins. The modification in the composition and content of fatty acids in the peanut kernels indicated that the nanoparticles could affect the quality of the crop.

Data on litterfall production and meteorology at an old-growth tropical dry forest in northwestern Mexico.

Chronological measurements of litterfall production can be used for understanding ecosystem dynamics such as net primary production and carbon cycling in highly seasonal ecosystems such as tropical dry forests (TDF). This paper presents data on litterfall production and meteorology in an old-growth TDF. The data was generated within the Monte Mojino Reserve located in the Sierra de Alamos - Rio Cuchujaqui Natural Protected Area in northwestern México. For litterfall collection, twenty randomly placed litterfall traps were installed to collect monthly litterfall production across four full growing seasons (48 monthly collections). Meteorological data were obtained from an automatic micrometeorological station that recorded data in situ from January 2013 to March 2019. The database includes litterfall production [g m-2 month-1], monthly rainfall [mm], air temperature [°C], relative humidity [%] and photosynthetic active radiation [µmol m-2 s-1].

Validation of a counseling guide for adherence to antiretroviral therapy using implementation science.

OBJECTIVE: to determine the contents that must be included in the usual counseling to improve the adherence to antiretroviral therapy (ART) of HIV patients, according to their different levels of alcohol consumption, and to determine the validity of the Counseling Guide in improving the adherence to ART in patients who consume alcohol using Implementation Science. METHOD: this is an observational study with formative and validation phases. The formative phase defined the content, approach and structure of the counseling. Validation included focus groups with patients and nurses, trial process by an expert and a pilot test. The criteria evaluated based on Implementation Science were: intervention source, evidence strength and quality, relative advantage, and complexity. The following criteria were also evaluated: usefulness, practicality, acceptability, sustainability, effectiveness; content consistency and congruence; procedural compliance and difficulties, and time spent in counseling. RESULTS: the strength of evidence of the counseling is High-IIA, with strong level of recommendation and presenting usefulness, practicality, acceptability, sustainability and effectiveness. Eight in 11 experts argued that the Guide is clear, consistent and congruent. Initial counseling takes around 24 minutes; and follow-up counseling, 21. The instruments of the Guide present reliability levels between good and high (0.65 ≥ alpha ≤ 0.92). CONCLUSION: the Counseling Guide is valid to improve the adherence to antiretroviral therapy in patients who consume alcohol.

Genotypic variations in leaf and whole-plant water use efficiencies are closely related in bread wheat genotypes under well-watered and water-limited conditions during grain filling.

Wheat plants growing under Mediterranean rain-fed conditions are exposed to water deficit, particularly during the grain filling period, and this can lead to a strong reduction in grain yield (GY). This study examines the effects of water deficit after during the grain filling period on photosynthetic and water-use efficiencies at the leaf and whole-plant level for 14 bread wheat genotypes grown in pots under glasshouse conditions. Two glasshouse experiments were conducted, one in a conventional glasshouse at the Universidad de Talca, Chile (Experiment 1), and another at the National Plant Phenomics Centre (NPPC), Aberystwyth, UK (Experiment 2), in 2015. Plants were grown under well-watered (WW) and water-limited (WL) conditions during grain filling. The reductions in leaf water potential (Ψ), net CO2 assimilation (An) and stomatal conductance (gs) due to water deficit were 79, 35 and 55%, respectively, during grain filling but no significant differences were found among genotypes. However, chlorophyll fluorescence parameters (as determined on dark-adapted and illuminated leaves) and chlorophyll content (Chl) were significantly different among genotypes, but not between water conditions. Under both water conditions, An presented a positive and linear relationship with the effective photochemical quantum yield of Photosystem II (Y(II)) and the maximum rate of electron transport (ETRmax), and negative with the quantum yield of non-photochemical energy conversion in Photosystem II (Y(NPQ)). The relationship between An and Chl was positive and linear for both water conditions, but under WL conditions An tended to be lower at any Chl value. Both, instantaneous (An/E) and intrinsic (An/gs) water-use efficiencies at the leaf level exhibited a positive and linear relationship with plant water-use efficiency (WUEp = plant dry weight/water use). Carbon discrimination (Δ13C) in kernels presented a negative relationship with WUEp, at both WW and WL conditions, and a positive relationship with GY. Our results indicate that during grain filling wheat plants face limitations to the assimilation process due to natural senesce and water stress. The reduction in An and gs after anthesis in both water conditions was mainly due a decline in the chlorophyll content (non-stomatal limitation), whereas the observed differences between water conditions were mainly due to a stomatal limitation.

Validation of a counseling guide for adherence to antiretroviral therapy using implementation science / Validação de um guia de aconselhamento para a adesão ao tratamento antirretroviral usando ciência da implementação / Validación de Guía de Consejería para adherencia al tratamiento antirretroviral usando ciencia de la implementación

Objective: to determine the contents that must be included in the usual counseling to improve the adherence to antiretroviral therapy (ART) of HIV patients, according to their different levels of alcohol consumption, and to determine the validity of the Counseling Guide in improving the adherence to ART in patients who consume alcohol using Implementation Science. Method: this is an observational study with formative and validation phases. The formative phase defined the content, approach and structure of the counseling. Validation included focus groups with patients and nurses, trial process by an expert and a pilot test. The criteria evaluated based on Implementation Science were: intervention source, evidence strength and quality, relative advantage, and complexity. The following criteria were also evaluated: usefulness, practicality, acceptability, sustainability, effectiveness; content consistency and congruence; procedural compliance and difficulties, and time spent in counseling. Results: the strength of evidence of the counseling is High-IIA, with strong level of recommendation and presenting usefulness, practicality, acceptability, sustainability and effectiveness. Eight in 11 experts argued that the Guide is clear, consistent and congruent. Initial counseling takes around 24 minutes; and follow-up counseling, 21. The instruments of the Guide present reliability levels between good and high (0.65 ≥ alpha ≤ 0.92). Conclusion: the Counseling Guide is valid to improve the adherence to antiretroviral therapy in patients who consume alcohol.

Objetivo: determinar os conteúdos que devem ser incluídos no aconselhamento habitual para melhorar a adesão ao TARV de pacientes com HIV, conforme seus diferentes níveis de consumo de álcool, e determinar a validade do Guia de Aconselhamento para melhorar a adesão ao TARV em pacientes que consomem álcool, usando a Ciência da Implementação. Método: estudo observacional com fase formativa e de validação. A fase formativa permitiu definir o conteúdo, a abordagem e a estrutura do aconselhamento. A validação incluiu grupos focais com pacientes e enfermeiras, processo de julgamento de especialista e teste piloto. Estes foram os critérios avaliados com base na Ciência da Implementação: fonte de intervenção, força e qualidade da evidência, vantagem relativa e complexidade. Foram avaliados ainda: utilidade, praticidade, aceitabilidade, sustentabilidade, efetividade; consistência e congruência do conteúdo; cumprimento, dificuldades do procedimento e tempo empregado no aconselhamento. Resultados: o aconselhamento tem força de evidência Alta -IIA, forte nível de recomendação, apresenta utilidade, praticidade, aceitabilidade, sustentabilidade e efetividade. Oito de 11 especialistas argumentaram que o Guia é claro, consistente e congruente. O aconselhamento de início leva em torno de 24 minutos; e o de acompanhamento, 21. Os instrumentos do Guia têm um nível de confiabilidade entre bom e alto (0,65 ≥ alfa ≤ 0,92). Conclusão: o guia de aconselhamento é válido para melhorar a adesão ao tratamento antirretroviral em pacientes que consomem álcool.

Objetivo: determinar los contenidos necesarios a incluir a la consejería habitual para mejorar la adherencia al TARV de pacientes con VIH según sus diferentes niveles de consumo de alcohol, y determinar la validez de la Guía de Consejería para mejorar la adherencia al TARV en paciente que consumen alcohol usando Ciencia de la Implementación. Método: estudio Observacional con fase formativa y de validación. La fase formativa permitió definir el contenido, enfoque y estructura de la consejería. La validación incluyó grupos focales con pacientes y enfermeras, juicio experto y prueba piloto. Los criterios evaluados en base a la Ciencia de la Implementación fueron: fuente de intervención, fuerza y calidad de la evidencia, ventaja relativa y complejidad. También se evaluó: utilidad, practicidad, aceptabilidad, sostenibilidad, efectividad; consistencia y congruencia del contenido; cumplimiento, dificultades del procedimiento y tiempo empleado en la consejería. Resultados: la consejería tiene fuerza de evidencia Alta -IIA, fuerte nivel de recomendación, presenta utilidad, practicidad, aceptabilidad, sostenibilidad y efectividad. Ocho de 11 expertos, sostuvieron que la Guía es clara, consistente y congruente. La consejería de inicio toma en promedio 24 minutos y 21 minutos la de seguimiento. Los instrumentos de la Guía tienen un nivel de fiabilidad entre bueno y alto (0,65 ≥ alfa ≤ 0,92). Conclusión: la guía de consejería es válida para mejorar la adherencia al tratamiento antirretroviral en pacientes que consumen alcohol.

Validation of a counseling guide for adherence to antiretroviral therapy using implementation science / Validação de um guia de aconselhamento para a adesão ao tratamento antirretroviral usando ciência da implementação / Validación de Guía de Consejería para adherencia al tratamiento antirretroviral usando ciencia de la implementación

Objective: to determine the contents that must be included in the usual counseling to improve the adherence to antiretroviral therapy (ART) of HIV patients, according to their different levels of alcohol consumption, and to determine the validity of the Counseling Guide in improving the adherence to ART in patients who consume alcohol using Implementation Science. Method: this is an observational study with formative and validation phases. The formative phase defined the content, approach and structure of the counseling. Validation included focus groups with patients and nurses, trial process by an expert and a pilot test. The criteria evaluated based on Implementation Science were: intervention source, evidence strength and quality, relative advantage, and complexity. The following criteria were also evaluated: usefulness, practicality, acceptability, sustainability, effectiveness; content consistency and congruence; procedural compliance and difficulties, and time spent in counseling. Results: the strength of evidence of the counseling is High-IIA, with strong level of recommendation and presenting usefulness, practicality, acceptability, sustainability and effectiveness. Eight in 11 experts argued that the Guide is clear, consistent and congruent. Initial counseling takes around 24 minutes; and follow-up counseling, 21. The instruments of the Guide present reliability levels between good and high (0.65 ≥ alpha ≤ 0.92). Conclusion: the Counseling Guide is valid to improve the adherence to antiretroviral therapy in patients who consume alcohol.

Objetivo: determinar os conteúdos que devem ser incluídos no aconselhamento habitual para melhorar a adesão ao TARV de pacientes com HIV, conforme seus diferentes níveis de consumo de álcool, e determinar a validade do Guia de Aconselhamento para melhorar a adesão ao TARV em pacientes que consomem álcool, usando a Ciência da Implementação. Método: estudo observacional com fase formativa e de validação. A fase formativa permitiu definir o conteúdo, a abordagem e a estrutura do aconselhamento. A validação incluiu grupos focais com pacientes e enfermeiras, processo de julgamento de especialista e teste piloto. Estes foram os critérios avaliados com base na Ciência da Implementação: fonte de intervenção, força e qualidade da evidência, vantagem relativa e complexidade. Foram avaliados ainda: utilidade, praticidade, aceitabilidade, sustentabilidade, efetividade; consistência e congruência do conteúdo; cumprimento, dificuldades do procedimento e tempo empregado no aconselhamento. Resultados: o aconselhamento tem força de evidência Alta -IIA, forte nível de recomendação, apresenta utilidade, praticidade, aceitabilidade, sustentabilidade e efetividade. Oito de 11 especialistas argumentaram que o Guia é claro, consistente e congruente. O aconselhamento de início leva em torno de 24 minutos; e o de acompanhamento, 21. Os instrumentos do Guia têm um nível de confiabilidade entre bom e alto (0,65 ≥ alfa ≤ 0,92). Conclusão: o guia de aconselhamento é válido para melhorar a adesão ao tratamento antirretroviral em pacientes que consomem álcool.

Objetivo: determinar los contenidos necesarios a incluir a la consejería habitual para mejorar la adherencia al TARV de pacientes con VIH según sus diferentes niveles de consumo de alcohol, y determinar la validez de la Guía de Consejería para mejorar la adherencia al TARV en paciente que consumen alcohol usando Ciencia de la Implementación. Método: estudio Observacional con fase formativa y de validación. La fase formativa permitió definir el contenido, enfoque y estructura de la consejería. La validación incluyó grupos focales con pacientes y enfermeras, juicio experto y prueba piloto. Los criterios evaluados en base a la Ciencia de la Implementación fueron: fuente de intervención, fuerza y calidad de la evidencia, ventaja relativa y complejidad. También se evaluó: utilidad, practicidad, aceptabilidad, sostenibilidad, efectividad; consistencia y congruencia del contenido; cumplimiento, dificultades del procedimiento y tiempo empleado en la consejería. Resultados: la consejería tiene fuerza de evidencia Alta -IIA, fuerte nivel de recomendación, presenta utilidad, practicidad, aceptabilidad, sostenibilidad y efectividad. Ocho de 11 expertos, sostuvieron que la Guía es clara, consistente y congruente. La consejería de inicio toma en promedio 24 minutos y 21 minutos la de seguimiento. Los instrumentos de la Guía tienen un nivel de fiabilidad entre bueno y alto (0,65 ≥ alfa ≤ 0,92). Conclusión: la guía de consejería es válida para mejorar la adherencia al tratamiento antirretroviral en pacientes que consumen alcohol.

Cirugía de hombro en posición silla de playa: estrategias y recomendaciones para la prevención de complicaciones isquémicas / Strategies and recommendations for the prevention of ischemic complications in beach chair position for shoulder surgery

Beach chair position is require for Shoulder surgery frequently for proper resolution. The stroke associated with shoulder surgery is a rare complication and probably underreported. The objective of this article is to review the pathophysiology of the ischemic damage associated with beach chair position, learn about strategies and develop recommendations to minimize risks.

La cirugía de hombro (CH), requiere y requerirá colocar a los pacientes en la posición en silla de playa (PSP), cada vez con mayor frecuencia para su adecuada resolución. El asociado a CH, es una complicación poco frecuente y probablmente subreportada. El objetivo de esta revisión, es repasar la fisiopatología del daño isquémico asociado a PSP, conocer estrategias y elaborar recomedaciones destinadas a minimizar riesgos.

Metabolic Effects of Elevated CO2 on Wheat Grain Development and Composition.

The increase in the atmospheric CO2 concentration is predicted to influence wheat production and grain quality and nutritional properties. In the present study, durum wheat (Triticum durum Desf. cv. Sula) was grown under two different CO2 (400 versus 700 µmol mol-1) concentrations to examine effects on the crop yield and grain quality at different phenological stages (from grain filling to maturity). Exposure to elevated CO2 significantly increased aboveground biomass and grain yield components. Growth at elevated CO2 diminished the elemental N content as well as protein and free amino acids, with a typical decrease in glutamine, which is the most represented amino acid in grain proteins. Such a general decrease in nitrogenous compounds was associated with altered kinetics of protein accumulation, N remobilization, and N partitioning. Our results highlight important modifications of grain metabolism that have implications for its nutritional quality.

Thermal Imaging Reliability for Estimating Grain Yield and Carbon Isotope Discrimination in Wheat Genotypes: Importance of the Environmental Conditions.

Canopy temperature (Tc) by thermal imaging is a useful tool to study plant water status and estimate other crop traits. This work seeks to estimate grain yield (GY) and carbon discrimination (Δ13C) from stress degree day (SDD = Tc - air temperature, Ta), considering the effect of a number of environmental variables such as the averages of the maximum vapor pressure deficit (VPDmax) and the ambient temperature (Tmax), and the soil water content (SWC). For this, a set of 384 and a subset of 16 genotypes of spring bread wheat were evaluated in two Mediterranean-climate sites under water stress (WS) and full irrigation (FI) conditions, in 2011 and 2012, and 2014 and 2015, respectively. The relationship between the GY of the 384 wheat genotypes and SDD was negative and highly significant in 2011 (r2 = 0.52 to 0.68), but not significant in 2012 (r2 = 0.03 to 0.12). Under WS, the average GY, Δ13C, and SDD of wheat genotypes growing in ten environments were more associated with changes in VPDmax and Tmax than with the SWC. Therefore, the amount of water available to the plant is not enough information to assume that a particular genotype is experiencing a stress condition.

Exploring Agronomic and Physiological Traits Associated With the Differences in Productivity Between Triticale and Bread Wheat in Mediterranean Environments.

In Mediterranean climates soil water deficit occurs mainly during the spring and summer, having a great impact on cereal productivity. While previous studies have indicated that the grain yield (GY) of triticale is usually higher than bread wheat (Triticum aestivum L.), comparatively little is known about the performance of these crops under water-limited conditions or the physiological traits involved in the different yields of both crops. For this purpose, two sets of experiments were conducted in order to compare a high yielding triticale (cv. Aguacero) and spring wheat (cvs. Pandora and Domo). The first experiment, aiming to analyze the agronomic performance, was carried out in 10 sites located across a wide range of Mediterranean and temperate environments, distributed between 33°34' and 38°41' S. The second experiment, aiming to identify potential physiological traits linked to the different yields of the two crops, was conducted in two Mediterranean sites (Cauquenes and Santa Rosa) in which crops were grown under well-watered (WW) and water-limited (WL) conditions. The relationship between GY and the environmental index revealed that triticale exhibited a higher regression coefficient (Finlay and Wilkinson slope), indicating a more stable response to the environment, accompanied by higher yields than bread wheat. Harvest index was not significantly different between the two cereals, but triticale had higher kernels per spike (35%) and 1000 kernel weight (16%) than wheat, despite a lower number of spikes per square meter. The higher yield of triticale was linked to higher values of chlorophyll content, leaf net photosynthesis (An), the maximum rate of electron transport (ETRmax), the photochemical quantum yield of PSII [Y(II)] and leaf water-use efficiency. GY was positively correlated with Ci at anthesis and Δ13C in both species, as well as with gs at anthesis in triticale, but negatively correlated with non-photochemical fluorescence quenching and quantum yield of non-photochemical energy conversion at grain filling in wheat. These results revealed that triticale presented higher photosynthetic rates that contributed to increase plant growth and yield in the different environments, whereas wheat showed higher photoprotection system in detriment of assimilate production.

Thalidomide protects against acute pentylenetetrazol and pilocarpine-induced seizures in mice.

Thalidomide was originally developed to treat primary neurological and psychiatric diseases. There are reports of anticonvulsant effects of thalidomide in rats and antiepileptic effects in patients. Hence, thalidomide (100, 200 and 400 mg/kg) was herein administered to mice to evaluate possible protection against seizures induced by the systemic administration of neurotoxins: 10 mg/kg of 4-aminopyridine (4-AP), 90 mg/kg of pentylenetetrazol (PTZ), or 380 mg/kg of pilocarpine. The effect of an NO and COX inhibitor (7-NI and ibuprofen, respectively) was also examined. The results show that thalidomide (1) induces the typical sedative effects, (2) has no anticonvulsant effect in mice treated with 4-AP, and (3) has anticonvulsant effect (400 mg/kg) in mice treated with PTZ and pilocarpine. It was found that 7-NI has an anticonvulsant effect in the pilocarpine model and that thalidomide's effect is not enhanced by its presence. However, thalidomide (200 mg/kg) plus 7-NI or ibuprofen tend to have a toxic effect in PTZ model. On the other hand, the combination of thalidomide and 7-NI or ibuprofen protects against pilocarpine-induced seizures. In conclusion, thalidomide did not exert an anticonvulsant effect for clonic-tonic type convulsions (4-AP), but it did so for seizures induced by PTZ and pilocarpine (representing absence seizures and status epilepticus, respectively). NO and prostaglandins were involved in the convulsive process elicited by pilocarpine.

The longitudinal effects of early developmental cadmium exposure on conditioned place preference and cardiovascular physiology in zebrafish.

Cadmium (Cd) is a naturally occurring trace metal that is widely considered to be highly toxic to aquatic organisms and a significant health hazard to humans (Amzal et al., 2009; Bernhoft 2013; Burger, 2008; Satarug et al., 2009). The zebrafish (Danio rerio) has been used as a model organism for toxicological studies with Cd (Banni et al., 2011; Blechinger et al., 2007; Chow et al., 2009; Chow et al., 2008; Favorito et al., 2011; Kusch et al., 2007; Matz et al., 2007; Wang and Gallagher, 2013). We asked what the lasting longitudinal effects would be from short early developmental Cd exposure (between 24 and 96h post-fertilization) in a range that larvae might experience living atop typical Cd-containing surface sediments (0, 0.01, 0.1, 1.0 and 10µM CdCl2: 1.124, 11.24, 112.4 and 1124µg Cd/L). The goal of this exposure window was to specifically target secondary neurogenesis, monoaminergic differentiation and cardiovascular development, without affecting earlier patterning processes. Developmental abnormalities in body size and CNS morphology increased with concentration, but were statistically significant only at the highest concentration used (10µM). Heart rate for Cd-treated larvae increased with concentration, and was significant even at the lowest concentration used (0.01µM). Longitudinal survival was significantly lower for fish developmentally exposed to the highest concentration. Except for brain weight, overall morphology was not affected by developmental Cd exposure. However, developmental exposure to lower concentrations of Cd (0.01, 0.1, and 1.0µM) progressively lowered cocaine-induced conditioned place preference (CPP), used to measure function of the reward pathways in the brain. Baseline heart rate was significantly lower in longitudinal fish developmentally exposed to 1.0µM Cd. Cardiovascular response to isoproterenol, a potent ß-adrenergic agonist, in longitudinal adults was also significantly affected by developmental exposure to Cd at low doses (0.01, 0.1 and 1.0µM). Surviving longitudinal adult fish exposed to the highest concentration of Cd showed normal CPP and cardiovascular physiology. The data imply that even lower exposure concentrations can potentially result in fitness-affecting parameters without affecting survival in a laboratory setting.