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A diagnostic of hypertension increases the risk of erectile dysfunction (ED); likewise, ED can be an early sign of hypertension. In both cases, there is evidence that endothelial dysfunction is a common link between the 2 conditions. During hypertension, the sustained and widespread release of procontractile factors (e.g., angiotensin II, endothelin 1, and aldosterone) impairs the balance between vasoconstrictors and vasodilators and, in turn, detrimentally impacts vascular and erectile structures. This prohypertensive state associates with an enhancement in the generation of reactive oxygen species, which is not compensated by internal antioxidant mechanisms. Recently, the innate immune system, mainly via Toll-like receptor 4, has also been shown to actively contribute to the pathophysiology of hypertension and ED not only by inducing oxidative stress but also by sustaining a low-grade inflammatory state. Furthermore, some drugs used to treat hypertension can cause ED and, consequently, reduce compliance with the prescribed pharmacotherapy. To break down these challenges, in this review, we focus on discussing the well-established as well as the emerging mechanisms linking hypertension and ED with an emphasis on the signaling network of the vasculature and corpora cavernosa, the vascular-like structure of the penis., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

We performed an integrative review on the scientific literature about the use of telehealth in audiology care. Through high criteria search of published studies on the "Biblioteca Virtual em Saúde" - Virtual Health Library, PubMed, and Scientific Electronic Library Online databases, nine articles were selected. It was possible to verify that the use of telehealth in audiology is feasible and efficient, because it could promote audiological care for patients from away places. This process reaches more patients and communities by breaking down geographic barriers, and it offers a specific service not available with less cost and more quickly when compared with traditional speech therapy care.

Heat-shock protein 70 (HSP70) is a ubiquitously expressed molecular chaperone with various biological functions. Recently, we demonstrated that HSP70 is key for adequate vascular reactivity. However, the specific mechanisms targeted by HSP70 to assist in this process remain elusive. Since there is a wealth of evidence connecting HSP70 to calcium ([Formula: see text]), a master regulator of contraction, we designed this study to investigate whether blockade of HSP70 disrupts vascular contraction via impairment of [Formula: see text] handling mechanisms. We performed functional studies in aortas isolated from male Sprague Dawley rats in the presence or absence of exogenous [Formula: see text], and we determined the effects of VER155008, an inhibitor of HSP70, on [Formula: see text] handling as well as key mechanisms that regulate vascular contraction. Changes in the intracellular concentration of [Formula: see text] were measured with a biochemical assay kit. We report that blockade of HSP70 leads to [Formula: see text] mishandling in aorta stimulated with phenylephrine, decreasing both phasic and tonic contractions. Importantly, in [Formula: see text] free Krebs' solution, inhibition of HSP70 only reduced the [Formula: see text] of the phasic contraction if the protein was blocked before IP3r-mediated [Formula: see text] release, suggesting that HSP70 has a positive effect towards this receptor. Corroborating this statement, VER155008 did not potentiate an IP3r inhibitor's outcomes, even with partial blockade. In another set of experiments, the inhibition of HSP70 attenuated the amplitude of the tonic contraction independently of the moment VER155008 was added to the chamber (i.e., whether it was before or after IP3r-mediated phasic contraction). More compelling, following re-addition of [Formula: see text], VER155008 amplified the inhibitory effects of a voltage-dependent [Formula: see text] channel blocker, but not of a voltage-independent [Formula: see text] channel inhibitor, indicating that HSP70 has a positive impact on the latter. Lastly, the mechanism by which HSP70 modulates vascular contraction does not involve the [Formula: see text] sensitizer protein, Rho-kinase, nor the SERCA pump, as blockade of these proteins in the presence of VER155008 almost abolished contraction. In summary, our findings shed light on the processes targeted by HSP70 during vascular contraction and open research avenues for potential new mechanisms in vascular diseases.

Competing Interests: Competing interests: None declared.

Forests are the largest terrestrial biomass pool, with over half of this biomass stored in the highly productive tropical lowland forests. The future evolution of forest biomass depends critically on the response of tree longevity and growth rates to future climate. We present an analysis of the variation in tree longevity and growth rate using tree-ring data of 3,343 populations and 438 tree species and assess how climate controls growth and tree longevity across world biomes. Tropical trees grow, on average, two times faster compared to trees from temperate and boreal biomes and live significantly shorter, on average (186 ± 138 y compared to 322 ± 201 y outside the tropics). At the global scale, growth rates and longevity covary strongly with temperature. Within the warm tropical lowlands, where broadleaf species dominate the vegetation, we find consistent decreases in tree longevity with increasing aridity, as well as a pronounced reduction in longevity above mean annual temperatures of 25.4 °C. These independent effects of temperature and water availability on tree longevity in the tropics are consistent with theoretical predictions of increases in evaporative demands at the leaf level under a warmer and drier climate and could explain observed increases in tree mortality in tropical forests, including the Amazon, and shifts in forest composition in western Africa. Our results suggest that conditions supporting only lower tree longevity in the tropical lowlands are likely to expand under future drier and especially warmer climates., Competing Interests: The authors declare no competing interest.

Tropical forests are being deforested worldwide, and the remaining fragments are suffering from biomass and biodiversity erosion. Quantifying this erosion is challenging because ground data on tropical biodiversity and biomass are often sparse. Here, we use an unprecedented dataset of 1819 field surveys covering the entire Atlantic Forest biodiversity hotspot. We show that 83-85% of the surveys presented losses in forest biomass and tree species richness, functional traits, and conservation value. On average, forest fragments have 25-32% less biomass, 23-31% fewer species, and 33, 36, and 42% fewer individuals of late-successional, large-seeded, and endemic species, respectively. Biodiversity and biomass erosion are lower inside strictly protected conservation units, particularly in large ones. We estimate that biomass erosion across the Atlantic Forest remnants is equivalent to the loss of 55-70 thousand km 2 of forests or US$2.3-2.6 billion in carbon credits. These figures have direct implications on mechanisms of climate change mitigation.

Dermatophytosis is a dermic disease caused by fungi. The aim of this study was to search anti-dermatophyte bioactive compounds in Piper umbellatum leaves. Cytotoxicity evaluation was performed against MRC-5 and HepG2 as a selectivity parameter. Crude ethanol extract presented MIC value of 39.1 μg/mL against M. canis and no cytotoxicity to Hep G2 (human liver cancer) and MRC-5 (normal lung fibroblast). 4-nerolydilcatechol was isolated from P. umbellatum ethanolic extract. MIC values for 4-NC were 7.6μM to M. canis and 15.6μM to Trichophyton rubrum. 4-NC presented activity against M. canis 14 times lower than to MRC-5 (non-tumoral human cell line), which suggest selective activity for this fungus. Molecular modeling suggests 4-NC could bind to CYP51, present in lanosterol synthesis, blocking fungi development. In conclusion, P. umbellatum crude ethanol extract and 4-NC demonstrated high and selective in vitro antifungal activity.[Formula: see text].

Vulvovaginal candidiasis is a serious health problem affecting numerous women around the world. Its treatment is based on antifungals which may not provide an effective cure because of the resistance presented by its etiological pathogens Candida spp. Candida albicans is the most prevalent species related to vulvovaginal candidiasis. Here, we evaluated the in vivo antifungal potential of thiosemicarbazide and thiosemicarbazide encapsulated within chitosan nanoparticles in a murine model of vulvovaginal candidiasis. The results demonstrated the antifungal capacity of free or nanoencapsulated thiosemicarbazide within chitosan to reduce the fungal load in the vaginal tissue of infected mice. In addition, histological analyses indicated the absence or a mild to moderate infection in thiosemicarbazide-treated groups. Statistical tests confirmed the existence of significant differences between the treated and the control groups. Therefore, our results suggest a potential application of thiosemicarbazide and encapsulated thiosemicarbazide as an alternative vulvovaginal candidiasis therapy.

Paracoccidioidomycosis is a neglected disease that causes economic and social impacts, mainly affecting people of certain social segments, such as rural workers. The limitations of antifungals, such as toxicity, drug interactions, restricted routes of administration, and the reduced bioavailability in target tissues, have become evident in clinical settings. These factors, added to the fact that Paracoccidioidomycosis (PCM) therapy is a long process, lasting from months to years, emphasize the need for the research and development of new molecules. Researchers have concentrated efforts on the identification of new compounds using numerous tools and targeting important proteins from Paracoccidioides , with the emphasis on enzymatic pathways absent in humans. This review aims to discuss the aspects related to the identification of compounds, methodologies, and perspectives when proposing new antifungal agents against PCM.

The present article reports the results of a systematic review on the potential benefits of the combined use of virtual reality (VR) and non-invasive brain stimulation (NIBS) as a novel approach for rehabilitation. VR and NIBS are two rehabilitation techniques that have been consistently explored by health professionals, and in recent years there is strong evidence of the therapeutic benefits of their combined use. In this work, we reviewed research articles that report the combined use of VR and two common NIBS techniques, namely transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). Relevant queries to six major bibliographic databases were performed to retrieve original research articles that reported the use of the combination VR-NIBS for rehabilitation applications. A total of 16 articles were identified and reviewed. The reviewed studies have significant differences in the goals, materials, methods, and outcomes. These differences are likely caused by the lack of guidelines and best practices on how to combine VR and NIBS techniques. Five therapeutic applications were identified: stroke, neuropathic pain, cerebral palsy, phobia and post-traumatic stress disorder, and multiple sclerosis rehabilitation. The majority of the reviewed studies reported positive effects of the use of VR-NIBS. However, further research is still needed to validate existing results on larger sample sizes and across different clinical conditions. For these reasons, in this review recommendations for future studies exploring the combined use of VR and NIBS are presented to facilitate the comparison among works.

Objective: to assess the effect of a breastfeeding educational intervention on the counseling provided to postpartum women., Method: this is a randomized controlled trial including 104 postpartum women (intervention group = 52 and control group = 52) from a private hospital, whose educational intervention was based on the pragmatic theory and on the use of a soft-hard technology called Breastfeeding Educational Kit (Kit Educativo para Aleitamento Materno, KEAM). Women were followed-up for up to 60 days after childbirth. Chi-Squared Test, Fischer's Exact Test, and Generalized Estimating Equation were used, with a significance level of 5% (p-value <0.05). The analyses were performed using the Statistical Package for the Social Sciences, version 24., Results: the postpartum women in the intervention group had fewer breastfeeding difficulties and a higher percentage of exclusive breastfeeding at all time points compared with those in the control group., Conclusion: the educational intervention based on active methodologies and stimulating instructional resources was effective in developing greater practical mastery among postpartum women with regard to adherence and maintenance of exclusive breastfeeding. Registry REBEC RBR - 8p9v7v.

Downy mildew, caused by Plasmopara viticola , is the main disease affecting vineyards in subtropical Brazil. Here, we collected 94 P. viticola isolates from four organic and conventional vineyards in the two main grape-growing states of Brazil to evaluate the sensitivity to the quinone outside inhibitor (QoI) azoxystrobin by pheno- and genotyping assays. The impact of location, production system and sensitivity to QoI fungicides on the population genetics and structure of P. viticola was determined using 10 microsatellite markers. Cytochrome b sequencing revealed that 28 and 100% of the isolates from vineyards under organic and conventional management carried the G143A mutation, respectively. The G143A mutation was associated with high levels of azoxystrobin resistance. Three out of the 94 isolates analyzed carried the M125I alteration, not previously described in P. viticola , which was associated with a five-fold reduction in azoxystrobin sensitivity compared to wild-type isolates. Haplotype network analysis based on cytochrome b gene sequences suggested that the Brazilian populations are more closely related to the European than the North American population. A total of six haplotypes were identified, with two of them carrying the G143A mutation. Microsatellite analysis revealed high allelic and genotypic variation among the four populations. Population differentiation analyses indicated that state of origin directly influences the population biology of P. viticola , while production system and QoI sensitivity have little effect. Great genetic diversity, sexual reproduction and high levels of admixture were observed in Rio Grande do Sul State. In contrast, populations in São Paulo State were dominated by a few clonal genotypes, and no admixed genotype was detected between the two genetic pools identified in the state. This study raises the hypothesis that winter weather conditions influence the overwinter survival strategy with profound effects in the population biology of P. viticola ., (Copyright © 2020 Santos, Ciampi-Guillardi, Fraaije, de Oliveira and Amorim.)

Hereditary myopathy with early respiratory failure is a neuromuscular disease with an autosomal dominant inheritance pattern. Clinical presentation is characterised by proximal and distal muscle weakness, exertional dyspnoea and generalised fatigue. There is no disease-modifying therapy and the prognosis is unknown. Herein we present a case of a 40-year-old woman with long-standing asthenia and apathy and, more recently, daytime sleepiness, dyspnoea and difficulty in walking. A hypercapnic respiratory failure with severe acidemia was identified. The muscle biopsy showed the presence of cytoplasmatic bodies and rimmed vacuoles, suggestive of a hereditary myopathy with early respiratory failure disease. The genetic study confirmed this diagnosis identifying a heterozygous mutation on c.95134T>C (p.Cys31712Arg) in exon 343 in the titin gene. The patient was discharged home under supportive treatment with non-invasive ventilation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: HSP70, a molecular chaperone, helps to maintain proteostasis. In muscle biology, however, evidence suggests HSP70 to have a more versatile range of functions, as genetic deletion of its inducible genes impairs Ca 2+ handling, and consequently, cardiac and skeletal muscle contractility. Still, it is unknown whether HSP70 is involved in vascular reactivity, an intrinsic physiological mechanism of blood vessels. Therefore, we designed this study to test the hypothesis that proper vascular reactivity requires the assistance of HSP70., Main Methods: We performed functional studies in a wire-myograph using thoracic aorta isolated from male Sprague Dawley rats. Experiments were conducted with and without an HSP70 inhibitor as well as in heat-stressed vessels. The expression levels of HSP70 were evaluated with Western blotting. NO and ROS levels were assessed with fluorescence microscopy., Key Findings: We report that blockade of HSP70 weakens contraction in response to phenylephrine (dose-response) in the aorta. Additionally, we demonstrated that inhibition of HSP70 affects the amplitude of the fast and of the slow components of the time-force curve. Corroborating these findings, we found that inhibition of HSP70, in vessels over-expressing this protein, partly rescues the contractile phenotype of aortic rings. Furthermore, we show that blockade of HSP70 facilitates relaxation in response to acetylcholine and clonidine without affecting the basal levels of NO and ROS., Significance: Our work introduces an additional physiological role for HSP70, the assistance of vascular reactivity, which highlights this protein as a new player in vascular physiology, and therefore, uncovers a promising research avenue for vascular diseases., Competing Interests: Declaration of competing interest Both authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: This study aimed to compare heart rate variability (HRV) parameters obtained through symbolic analysis (SA), between older adults with and without hyperuricemia., Methods: This is a cross-sectional study including 202 community-dwelling old adults, which was clinically stratified as with or without hyperuricemia, according to the cutoff point of serum uric acid ≥ 6 mg/dL for women and ≥ 7 mg/dL for men. Successive RR intervals were recorded along 5 min and analyzed with SA method. 0 V%, 1 V% and 2 V% patterns were quantified and compared between groups. Comparisons were carried out through parametric or nonparametric tests, according to the data distribution characteristics, evaluated by Kolmogorov-Smirnov test. The significance level was set as p ≤ 0.05 for all statistical procedures., Results: The prevalence of hyperuricemia was 67.8 %, and the hyperuricemic older adults exhibited significant higher values for V0% and lower values for V2% parameters when compared to normouricemic older adults., Conclusion: These results suggesting a sympathovagal imbalance in hyperuricemic older adults, characterized by greater sympathetic predominance (0 V%) and lower vagal modulation (2 V%) at rest conditions., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The current study was carried out by a bioguided fractionation of a hexane extract of the latex of Euphorbia umbellata against leukemic cells. Samples were analyzed by NMR, GC/MS, triterpenes quantification, and MTT reduction assay. Morphological, cell cycle, mitochondrial membrane potential and caspases 3/7 analyses were performed for the dichloromethane and ethanol fractions, and selectivity index for the dichloromethane fraction. NMR analysis presented characteristic signals of terpenes and steroids, data were confirmed by the quantification of triterpenes and GC/MS analysis. MTT reduction assay demonstrated that HL-60 was the most sensitive cell lineage against dichloromethane and ethanol fractions. Compounds of these matrices caused morphological changes compatible with apoptosis induction, altered cell cycle, increment of depolarized population cells and activation of caspases 3/7. Selectivity indices were higher than 22.44. Bioguided-fractionation study showed that samples of the latex of E. umbellata raised the activity of the phytocomplex against leukemic cells, and the cytotoxicity can be associated with an apoptosis pathway., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Genomic selection has become a reality in plant breeding programs with the reduction in genotyping costs. Especially in maize breeding programs, it emerges as a promising tool for predicting hybrid performance. The dynamics of a commercial breeding program involve the evaluation of several traits simultaneously in a large set of target environments. Therefore, multi-trait multi-environment (MTME) genomic prediction models can leverage these datasets by exploring the correlation between traits and Genotype-by-Environment (G×E) interaction. Herein, we assess predictive abilities of univariate and multivariate genomic prediction models in a maize breeding program. To this end, we used data from 415 maize hybrids evaluated in 4 years of second season field trials for the traits grain yield, number of ears, and grain moisture. Genotypes of these hybrids were inferred in silico based on their parental inbred lines using single nucleotide polymorphisms (SNPs) markers obtained via genotyping-by-sequencing (GBS). Because genotypic information was available for only 257 hybrids, we used the genomic and pedigree relationship matrices to obtain the H matrix for all 415 hybrids. Our results demonstrated that in the single-environment context the use of multi-trait models was always superior in comparison to their univariate counterparts. Besides that, although MTME models were not particularly successful in predicting hybrid performance in untested years, they improved the ability to predict the performance of hybrids that had not been evaluated in any environment. However, the computational requirements of this kind of model could represent a limitation to its practical implementation and further investigation is necessary.

While the pathogenesis of diabetes-induced high blood pressure (BP) is not entirely clear, current evidence suggests that Toll-like receptor 4 (TLR4) is a key player in the mechanisms associated with hypertension. However, it is unknown whether this receptor affects BP under type 1 diabetes. Likewise, there is insufficient knowledge about the role of TLR4 in diabetes-associated vascular dysfunction of large arteries. To narrow these gaps, in this study, we investigated if blockade of the TLR4-MD2 complex impacts BP and vascular function in diabetic rats. We injected streptozotocin in male Sprague Dawley rats and treated them with a neutralizing anti-TLR4 antibody for 14 days. BP was directly measured in conscious animals at the end of the treatment. In another set of experiments, we excised the aorta from control and diabetic animals, and measured TLR4 and MD2-a co-receptor that confers functionality to TLR4-levels by Western blotting. We also performed functional studies and evaluated ROS levels with and without a pharmacological inhibitor for TLR4 as well as for MD2. Additionally, we scrutinized a large human RNA-Seq dataset of aortic tissue to assess the co-expression of TLR4, MD2, and subunits of the vascular NADPH oxidases under diabetes and hypertension. We report that (a) chronic blockade of the TLR4-MD2 complex lowers BP in diabetic animals; that (b) type 1 diabetes modulates the levels of MD2 expression in the aorta, but not TLR4, at least in the conditions evaluated in this study; and, that (c) acute inhibition of TLR4 or MD2 diminishes vascular contractility and reduces oxidative stress in the aorta of these animals. In summary, we show evidence that the TLR4-MD2 complex is involved in the mechanisms linking type 1 diabetes and hypertension.

Amazonian forests are extraordinarily diverse, but the estimated species richness is very much debated. Here, we apply an ensemble of parametric estimators and a novel technique that includes conspecific spatial aggregation to an extended database of forest plots with up-to-date taxonomy. We show that the species abundance distribution of Amazonia is best approximated by a logseries with aggregated individuals, where aggregation increases with rarity. By averaging several methods to estimate total richness, we confirm that over 15,000 tree species are expected to occur in Amazonia. We also show that using ten times the number of plots would result in an increase to just ~50% of those 15,000 estimated species. To get a more complete sample of all tree species, rigorous field campaigns may be needed but the number of trees in Amazonia will remain an estimate for years to come.

Herein we report the first recorded arrival of Aedes aegypti on Trindade Island, approximately 1,140 km from the Brazilian coast, posing potential health risks to the human inhabitants thereof. The collection of mosquitoes was done from August to October 2019 via an active search for adults, eggs, and larvae by surveying objects with accumulated water and implantation of 23 ovitraps in different regions of the island. As a result, we collected 33 adults of Ae. aegypti via active search inside buildings. A total of 433 eggs of Ae. aegypti were also obtained from the ovitraps, all of which subsequently reached the adult stage. No other species of Culicidae was found., (Copyright © 2020 by The American Mosquito Control Association, Inc.)

Background: The integration of occupational risk management initiatives and health promotion and well-being in the workplace poses a challenge to organizations from different sectors., Objective: Cross-cultural adaptation of the Dimensions of Corporate Well-Being Scorecard (DCWS) to the Brazilian Portuguese language., Method: The process of cross-cultural adaptation of the Dimensions of Corporate Well-Being Scorecard to the Brazilian Portuguese language evolved along six steps: translation, reconciliation, back-translation, revision by internal expert committee, revision by expert panel (pretest) and final revision., Results: The stringent protocols adopted in the present study resulted in a satisfactory and adequate instrument to analyze programs which target workers' health, safety and well-being at organizations operating in Brazil., Conclusion: The Brazilian version of DCWS, entitled Questionário sobre as Dimensões do Bem-Estar Corporativo (QDBC) represents an advance in the evaluation of the effectiveness of integrated actions for health promotion and workers' well-being in different work environments.

Objective: To generate reference values for spirometry in Brazilian children 3-12 years of age and to compare those values with the values employed in the equations currently in use in Brazil., Methods: This study involved healthy children, 3-12 years of age, recruited from 14 centers (primary data) and spirometry results from children with the same characteristics in six databases (secondary data). Reference equations by quantile regressions were generated after log transformation of the spirometric and anthropometric data. Skin color was classified as self-reported by the participants. To determine the suitability of the results obtained, they were compared with those predicted by the equations currently in use in Brazil., Results: We included 1,990 individuals from a total of 21 primary and secondary data sources. Of those, 1,059 (53%) were female. Equations for FEV1, FVC, the FEV1/FVC ratio, FEF between 25% and 75% of the FVC (FEF25-75%) and the FEF25-75%/FVC ratio were generated for white-, black-, and brown-skinned children. The logarithms for height and age, together with skin color, were the best predictors of FEV1 and FVC. The reference values obtained were significantly higher than those employed in the equations currently in use in Brazil, for predicted values, as well as for the lower limit of normality, particularly in children with self-reported black or brown skin., Conclusions: New spirometric equations were generated for Brazilian children 3-12 years of age, in the three skin-color categories defined. The equations currently in use in Brazil seem to underestimate the lung function of Brazilian children 3-12 years of age and should be replaced by the equations proposed in this study.

Grapevine physiology is influenced by several environmental factors, such as temperature, precipitation, potential evapotranspiration, and sunshine hours. Due to climatic changes, effects in grapevine physiology and consequently on the grape berry composition and quality have been observed. This work aims to make a comparative study of the effect of foliar mitigation treatment with kaolin (5%) and potassium silicates (0.1% and 0.05%) on the grape berry quality; namely on berry weight, pH, probable alcohol, total phenolics, tannins, total anthocyanins, monomeric anthocyanins, calcium, potassium, and magnesium composition from Portuguese grapevines ( Vitis vinifera L. cv. Touriga Nacional and Touriga Franca). The results suggested that the phenolic composition and anthocyanin content differs between treatments while other parameters showed distinct behavior among the different applications. Qualitative parameters observed in the present study suggested non-significant changes upon both the applications.

Aims: Hyperglycemia in combination with oxidative stress plays a significant pathophysiological role in diabetic testicular dysfunction, often leading to infertility. Activation of Toll-like receptor 4 (TLR4) has been reported to mediate oxidative stress during diabetes. However, engagement of the TLR4 signaling pathway in diabetic testicular dysfunction has not been previously explored. Herein, we investigated the role of TLR4 in reactive oxygen species (ROS) production and in the phosphorylation status of ERK1/2 in primary Leydig cells exposed to high glucose and in testis isolated from diabetic rats., Main Methods: Testicular levels of TLR4 and phospho-ERK1/2 were determined by Western blotting. ROS production was detected with a fluorescent probe. Additionally, primary Leydig cells were exposed to normal (5.5 mmol/l) or elevated (33 mmol/l) glucose concentrations and treated with or without a TLR4 inhibitor, CLI095 (10 - 5  mol/l) for 24 h, followed by evaluation of TLR4 and phospho-ERK1/2 expression levels by Western blotting and immunofluorescence staining, respectively., Key Findings: We show that high glucose induces the expression of TLR4 in Leydig cells. Additionally, we demonstrate that blockade of this receptor in this cell population reduces oxidative stress and restores the levels of phospho-ERK1/2., Significance: Our findings provide new insight into TLR4 interaction with ROS and MEK/ERK pathway in Leydig cells exposed to high glucose and present a rationale for the development of new therapeutics for diabetic testicular dysfunction., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Few studies have examined the influence of reservoir hydrodynamics on the water quality of its limnological zones. In this study, the relationships between the operational phases and the water quality of the limnological zones were assessed for the Amazonian reservoir Tucuruí. Limnological zones were clustered by means of an artificial neural network technique, and inputs used were water quality variables, measured at twelve stations between 2006 and 2016. Generalized Linear Models (GLMs) were then used to identify the influence of the operational phases of the reservoir on the water quality of its limnological zones. The GLM with a gamma-distributed response variable indicated that Chlorophyll-a concentrations in the riverine and transitional zones differed notably from those observed in the lacustrine zone. Chlorophyll-a concentrations were significantly lower during the operational falling water phase than in the low water phase (p < 0.05). The GLM with an inverse Gaussian-distributed response variable indicated that Secchi depth was significantly lower in the riverine than in the lacustrine limnological zone (p < 0.05). Our results suggest that more eutrophic conditions occur during the operational rising water phase, and that the area most vulnerable to eutrophication is the transitional zone. We demonstrate that the use of GLMs is suitable for determining areas and operational phases most vulnerable to eutrophication. We envisage that this information will be useful to decision-makers when monitoring the water quality of hydroelectric reservoirs with dendritic patterns and dynamic operational phases., Competing Interests: Declaration of competing interest None declared., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Monophasic Zn 1-x Fe x O nanoparticles with wurtzite structure were synthesized in the 0 ≤ x ≤ 0.05 concentration range using a freeze-drying process followed by heat treatment. The samples were characterized regarding their optical, structural, and magnetic properties. The analyses revealed that iron doping of the ZnO matrix induces morphological changes in the crystallites. Iron is substitutional for zinc, trivalent and distributed in the wurtzite lattice in two groups: isolated iron atoms and iron atoms with one or more neighboring iron atoms. It was also shown that the energy band gap decreases with a higher doping level. The samples are paramagnetic at room temperature, but they undergo a spin-glass transition when the temperature drops below 75 K. The magnetic frustration is attributed to the competition of magnetic interactions among the iron moments. There are a superexchange interaction and an indirect exchange interaction that is provided by the spin (and charge) itinerant carriers in a spin-polarized band situated in the vicinity of the Fermi level of the Fe-doped ZnO semiconductor. The former interaction actuates for an antiferromagnetic coupling among iron ions, whereas the latter constitutes a driving force for a ferromagnetic coupling that weakens, decreasing the temperature. Our results strongly contribute to the literature because they elucidate the controversies reported in the literature for the magnetic state of the Fe-doped ZnO system.

Background: Broad-encompassing approaches to the evaluation, documentation and discussion of workplace health assets are needed to implement effective interventions and promote health and well-being among workers through effective efforts in programs and initiatives to maintain and improve workplace health and safety., Objective: To perform the cross-cultural adaptation of the Indicators of Integration (II) scorecard to the Brazilian Portuguese language to enable its use in Brazil and thus provide organizations a means to evaluate the integration of workers' health and well-being programs, policies and practices., Methods: We followed scientific recommendations described in previous studies and carried out the process of adaptation along six steps: translation, reconciliation of translations, back translation into the original language, revision of the Portuguese version by an internal expert committee, pretest with an expert panel, and final review., Results: The methods applied resulted in an adequate instrument for self-evaluation of the integration of workers' health and well-being programs and practices in organizations; the adapted version conserves the properties of the original., Conclusion: The Brazilian version of the II scorecard - entitled Indicadores Integrados de Práticas de Saúde na Organização (IIPSO) - obtained in the present study is appropriate to be administered and to measure the implementation and integration of health, safety and well-being actions.

The mosquito Aedes aegypti is the vector of arboviruses such as Zika, Chikungunya, dengue and yellow fever. These infectious diseases have a major impact on public health. The unavailability of effective vaccines or drugs to prevent or treat most of these diseases makes vector control the main form of prevention. One strategy to promote mosquito population control is the use of synthetic insecticides to inhibit key enzymes in the metabolic pathway of these insects, particularly during larval stages. One of the main targets of the kynurenine detoxification pathway in mosquitoes is the enzyme 3-hydroxykynurenine transaminase (HKT), which catalyzes the conversion of 3-hydroxykynurenine (3-HK) into xanthurenic acid (XA). In this work, we report eleven newly synthesized oxadiazole derivatives and demonstrate that these compounds are potent noncompetitive inhibitors of HKT from Ae. aegypti. The present data provide direct evidence that HKT can be explored as a molecular target for the discovery of novel larvicides against Ae. aegypti. More importantly, it ensures that structural information derived from the HKT 3D-structure can be used to guide the development of more potent inhibitors., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To verify if structural aspects, previous use of digital technologies, and ways of studying by classroom attendance students interfere with motivation in the use of these technologies in online courses., Method: A quantitative cross-sectional study was carried out with 713 university students, from May to September 2015, with the use of an evaluation scale for motivational factors regarding the integration of information and communication technologies in education. Descriptive and inferential statistical analysis of the data was carried out., Results: Desire to attend online courses interfered with four of the five scale factors. Having a space for studying and the way students reported learning better interfered with intrinsic motivation (p=0.006 and p=0.017, respectively)., Conclusion: Predisposition to attend online courses, having an appropriate space to study, and reconciling studies with the use of other websites were positive elements for motivation of students in online courses.

Chitosan is an environmentally-friendly active molecule that has been explored for numerous agricultural uses. Its use in crop protection is well-known, however, other properties, such as bioactivity, deserve attention. Moreover, the modes of actions of chitosan remain to be elucidated. The present study assessed the levels of total phenolic compounds, the antioxidant potential, and the expression of reactive oxygen species (ROS) scavenging genes in the berries (skins and seeds), leaves, cluster stems, and shoots upon chitosan application on two red grapevine varieties (Touriga Franca and Tinto Cão). The application of chitosan on the whole vine before and after veraison led to the increased levels of polyphenols, anthocyanins, and tannins in Tinto Cão berries, and polyphenols and tannins in Touriga Franca berries, respectively. CUPric Reducing Antioxidant Capacity (CUPRAC) and Ferric Reducing Antioxidant Power (FRAP) assays indicated an increase in the antioxidant potential of berries. With the exception of ascorbate peroxidase (APX), all the ROS pathway genes tested, i.e., iron-superoxide dismutase (Fe-SOD), copper-zinc-superoxide dismutase (Cu/Zn-SOD), catalase (CAT), glutathione reductase (GR), glutaredoxin (Grx), respiratory burst oxidase (Rboh), amine oxidase (AO), peroxidase (POD) and polyphenol oxidase (PPO), were found up-regulated in chitosan-treated berries. Results from the analyses of leaves, stems, and shoots revealed that chitosan not only induced the synthesis of phenolic compounds but also acted as a facilitator for the transfer of polyphenols from the leaves to the berries., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors.

Purpose: This study investigated the effects of two levels of noise on the performance of young students of three educational levels and tested their ability to maintain attentional focus in reading and writing tasks., Methods: 162 school children in the third, fourth and fifth grades were placed in three groups according to their educational level: Control Group (CG), Experimental Group A (GEA) and Experimental Group B (GEB). All groups were submitted to a Sustained Attention Test, Reading Assessment and Isolated Words Test and Writing Dictation Sub-test (part of the International Dyslexia Test). The GEA and GEB performed the tests in a noisy environment: 20dB and 40dB, respectively. The CG was assessed in the usual school environmental noise at the same time of the day. The data was submitted to an ANOVA, the Kruskal-Wallis test and Spearman correlation test., Results: The higher the score on the Sustained Attention Test, the shorter the time spent reading and fewer errors in the dictation task. There were no differences across the three grades within the GEA (lower levels of noise) with regard to the effect of noise on attention and in the reading and writing task performance. The higher levels of noise for the GEB, however, decreased the attention levels, therefore increasing mistakes on the dictation test. Comparing the performance across educational levels on the reading tasks, the fourth grade presented decreased reading time, while the third and fifth grades spent more time reading., Conclusion: Auditory interference can influence the ability to focus attention as well as worsen performance in reading and writing tasks at more intense noise levels.

While precise mechanisms underlying cardiovascular diseases (CVDs) are still not fully understood, previous studies suggest that the innate immune system, through Toll-like receptor 4 (TLR4), plays a crucial part in the pathways leading to these diseases, mainly because of its interplay with endogenous molecules. The Heat-shock protein 70 family (HSP70-70kDa) is of particular interest in cardiovascular tissues as it may have dual effects when interacting with TLR4 pathways. Although the hypothesis of the HSP70 family members acting as TLR4 ligands is becoming widely accepted, to date no co-crystal structure of this complex is available and it is still unknown whether this process requires the co-adaptor MD2. In this study, we aimed at investigating the interplay between the TLR4/MD2 complex and HSP70 family members in the human cardiovascular system through transcriptomic data analysis and at proposing a putative interaction model between these proteins. We report compelling evidence of correlated expression levels between TLR4 and MD2 with HSP70 cognate family members, especially in heart tissue. In our molecular docking simulations, we found that HSP70 in the ATP-bound state presents a better docking score towards the TLR4/MD2 complex compared to the ADP-bound state (-22.60 vs. -10.29 kcal/mol, respectively). Additionally, we show via a proximity ligation assay for HSP70 and TLR4, that cells stimulated with ATP have higher formation of fluorescent spots and that MD2 might be required for the complexation of these proteins. The insights provided by our computational approach are potential scaffolds for future in vivo studies investigating the interplay between the TLR4/MD2 complex and HSP70 family members in the cardiovascular system.

Paracoccidioidomycosis (PCM) is the most prevalent endemic mycosis in Latin America. The disease is caused by fungi of the genus Paracoccidioides and mainly affects low-income rural workers after inhalation of fungal conidia suspended in the air. The current arsenal of chemotherapeutic agents requires long-term administration protocols. In addition, chemotherapy is related to a significantly increased frequency of disease relapse, high toxicity, and incomplete elimination of the fungus. Due to the limitations of current anti-PCM drugs, we developed a computational drug repurposing-chemogenomics approach to identify approved drugs or drug candidates in clinical trials with anti-PCM activity. In contrast to the one-drug-one-target paradigm, our chemogenomics approach attempts to predict interactions between drugs, and Paracoccidioides protein targets. To achieve this goal, we designed a workflow with the following steps: (a) compilation and preparation of Paracoccidioides spp. genome data; (b) identification of orthologous proteins among the isolates; (c) identification of homologous proteins in publicly available drug-target databases; (d) selection of Paracoccidioides essential targets using validated genes from Saccharomyces cerevisiae ; (e) homology modeling and molecular docking studies; and (f) experimental validation of selected candidates. We prioritized 14 compounds. Two antineoplastic drug candidates (vistusertib and BGT-226) predicted to be inhibitors of phosphatidylinositol 3-kinase TOR2 showed antifungal activity at low micromolar concentrations (<10 μM). Four antifungal azole drugs (bifonazole, luliconazole, butoconazole, and sertaconazole) showed antifungal activity at low nanomolar concentrations, validating our methodology. The results suggest our strategy for predicting new anti-PCM drugs is useful. Finally, we could recommend hit-to-lead optimization studies to improve potency and selectivity, as well as pharmaceutical formulations to improve oral bioavailability of the antifungal azoles identified.

Objective: It was aimed to assess the factors associated with the lifestyle of high school students from public schools., Method: Cross-sectional and analytical study, in Montes Claros, Minas Gerais. 819 high school students from state public schools participated in 2016/2017. A questionnaire was used that included sociodemographic, school variables, self-perception of quality of life, depressive symptoms, Internet addiction and lifestyle. The Chances Ratio was used, through Logistic Regression., Results: Among the participants, 92.2% had a desirable lifestyle, with a mean score of 70.75 points (±11.60). In the multiple analysis, the variables self-perception of quality of life (p= 0.005), depressive symptoms (p<0.001) and Internet addiction (p=0.007) remained associated with lifestyle., Conclusion: The improvement of the quality of life, emotional support and education regarding the adequate use of the Internet should be addressed by the nurse in actions to promote health in the school environment.

Hyperglycemia is a chief factor in diabetes, a complex disease associated with reproductive disorders, mainly testicular dysfunction, which contributes to male infertility. Leydig cells are the predominant cell population in the testis interstitium and, when stimulated, they are capable of initiating immune responses playing crucial roles in the mechanisms related to testis' homeostasis. These cells express TLR4, an innate immune receptor, which is known to be modulated by hyperglycemia in other cell populations and tissue types. Still, whether TLR4 contributes to hyperglycemia-associated testicular dysfunction remains elusive. Activation of TLR4 in response to high glucose levels involves redox imbalance and stimulation of transcriptional factors, especially nuclear factor (NF)-κB, which could be a potential pathological mechanism compromising the testis integrity. Additionally, emerging evidence shows crosstalk between TLR4 and Nrf2, an anti-inflammatory mediator that was previously shown to be reduced in diabetic testis. Therefore, we hypothesize that hyperglycemia-mediated TLR4 activation in testicular cells, especially Leydig cells might be a crucial event triggering oxidative stress and inflammation, which in turn, drives testicular dysfunction., (Copyright © 2019. Published by Elsevier Ltd.)

The immune system plays a prominent role in the initiation and maintenance of hypertension. The innate immune system, via toll-like receptors (TLRs), identifies distinct signatures of invading microbes and damage-associated molecular patterns and triggers a chain of downstream signalling cascades, leading to secretion of pro-inflammatory cytokines and shaping the adaptive immune response. Over the past decade, a dysfunctional TLR-mediated response, particularly via TLR4, has been suggested to support a chronic inflammatory state in hypertension, inducing deleterious local and systemic effects in host cells and tissues and contributing to disease progression. While the underlying mechanisms triggering TLR4 need further research, evidence suggests that sustained elevations in BP disrupt homeostasis, releasing endogenous TLR4 ligands in hypertension. In this review, we discuss the emerging role of TLR4 in the pathogenesis of hypertension and whether targeting this receptor and its signalling pathways could offer a therapeutic strategy for management of this multifaceted disease. LINKED ARTICLES: This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc., (© 2018 The British Pharmacological Society.)

DNA adducts and oxidized DNA bases are examples of DNA lesions that are useful biomarkers for the toxicity assessment of substances that are electrophilic, generate reactive electrophiles upon biotransformation, or induce oxidative stress. Among the oxidized nucleobases, the most studied one is 8-oxo-7,8-dihydroguanine (8-oxoGua) or 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), a biomarker of oxidatively induced base damage in DNA. Aldehydes and epoxyaldehydes resulting from the lipid peroxidation process are electrophilic molecules able to form mutagenic exocyclic DNA adducts, such as the etheno adducts 1,N 2 -etheno-2'-deoxyguanosine (1,N 2 -εdGuo) and 1,N 6 -etheno-2'-deoxyadenosine (1,N 6 -εdAdo), which have been suggested as potential biomarkers in the pathophysiology of inflammation. Selective and sensitive methods for their quantification in DNA are necessary for the development of preventive strategies to slow down cell mutation rates and chronic disease development (e.g., cancer, neurodegenerative diseases). Among the sensitive methods available for their detection (high performance liquid chromatography coupled to electrochemical or tandem mass spectrometry detectors, comet assay, immunoassays, 32 P-postlabeling), the most selective are those based on high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-ESI-MS/MS). Selectivity is an essential advantage when analyzing complex biological samples and HPLC-ESI-MS/MS evolved as the gold standard for quantification of modified nucleosides in biological matrices, such as DNA, urine, plasma and saliva. The use of isotopically labeled internal standards adds the advantage of corrections for molecule losses during the DNA hydrolysis and analyte enrichment steps, as well as for differences of the analyte ionization between samples. It also aids in the identification of the correct chromatographic peak when more than one peak is present. We present here validated sensitive, accurate and precise HPLC-ESI-MS/MS methods that were successfully applied for the quantification of 8-oxodGuo, 1,N 6 -dAdo and 1,N 2 -dGuo in lung, liver and kidney DNA of A/J mice for the assessment of the effects of ambient PM2.5 exposure.

Nunes, PRP, Barcelos, LC, Oliveira, AA, Furlanetto, R, Martins, FM, Resende, EAMR, and Orsatti, FL. Muscular strength adaptations and hormonal responses after two different multiple-set protocols of resistance training in postmenopausal women. J Strength Cond Res 33(5): 1276-1285, 2019-We studied the effects of 2 different resistance training (RT) multiple-set protocols (3 and 6 sets) on muscle strength and basal hormones concentrations in postmenopausal women (PW). Postmenopausal women were randomly allocated into 3 groups: control (CT, n = 12), low RT volume (LV = 3 sets for each exercise, n = 10), and high RT volume (HV = 6 sets for each exercise, n = 12). The LV and HV groups performed 8 exercises of a total body RT protocol 3 times a week, at 70% of 1 repetition maximum (1RM) for 16 weeks. Muscle strength and basal hormone concentrations were measured before and after RT. Our findings show that 3 sets or 6 sets at 70% of 1RM protocol increased muscular strength similarly after 16 weeks (sum of all exercises, LV: 37.7% and HV: 34.1% vs. CT: 2.1%, p < 0.001). Moreover, the RT volume does not affect basal levels of testosterone (TT) (LV: 0.02%, HV: -0.12%, and CT: 0.006%, p = 0.233), cortisol (C) (LV: 72.4%, HV: 36.8%, and CT: 16.8%, p = 0.892), insulin-like growth factor-1 (LV: 6.7%, HV: 7.3%, and CT: 4.1%, p = 0.802), dehydroepiandrosterone sulfate (LV: 0.1%, HV: -4.5%, and CT: -6.7%, p = 0.885), and TT:C ratio (LV: -0.9%, HV: -1.6%, and CT: -0.4%, p = 0.429). Our results suggest that 3 sets and 6 sets at 70% of 1RM seem to promote similar muscle strength gain. Thus, 3-set RT is a time efficient protocol for strength gain after 16 weeks in PW.

Pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs) play crucial roles in the underlying mechanisms of metabolic syndrome (MetS). Mainly, these receptors have been suggested to participate in the pathophysiological processes involved in the complications associated with this condition. Therefore, to evolve therapeutic strategies targeting PRRs might be an imperative approach to avoid the development of further complications in human subjects. In this work, we discuss the understanding regarding the roles of PRRs in the pathways of MetS to further describe potential advancements made to target these receptors within this pathology., (Copyright © 2019. Published by Elsevier Ltd.)

Parkinson's disease (PD) is a very common neurodegenerative condition in which both motor and nonmotor deficits evolve throughout the course of the disease. Normally characterized as a movement disorder, PD has been broadly studied from a motor perspective. However, mild to moderate cognitive deficits began to appear in the early phases of the disease, even before motor disturbances actually manifest, and continue to progress relentlessly. These nonmotor manifestations are also a source of detriment to the patients' already strained functionality and quality of life, and pose a therapeutic challenge seeing that replacing therapies have had conflicting results. Considering that the currently approved therapies can hardly be considered curative, efforts to find therapeutic approaches with an actual disease-modifying quality and capable of addressing not only motor but also cognitive dysfunctions are clearly needed. Among possible alternatives with such attribute, mesenchymal stem cell transplantation and exercise are worth highlighting given their common neuroprotective, neuroplastic, and immunomodulatory properties. In this paper, we will summarize the existent literature on the topic, focusing on the mechanisms of action through which these two approaches might beget therapeutic benefits for PD beyond the commonly assessed motor dysfunctions, alluding, at the same time, toward a potential synergic association of both therapies as an optimized approach for PD.

This study proposed the application of structural equation modeling (SEM) to investigate variables associated with preterm birth based on a theoretical model analyzed previously by hierarchical logistic regression. The data came from a population-based case-control observational study of hospital births to mothers residing in Londrina, Paraná State, Brazil (June 2006 to March 2007). For the SEM, the study considered the association between socioeconomic characteristics and psychosocial aspects pertaining to reproductive history, work and physical activity, complications during the pregnancy, and fetal characteristics. It also considered the relationship between these associations and the outcome preterm birth mediated by adequacy of prenatal care. The weighted least square mean and variance adjusted estimator (WLSMV) was used for categorical data and robust maximum likelihood (MLR) for odds ratios. Three latent variables were created: socioeconomic vulnerability, family vulnerability, and unwanted pregnancy. The effect of socioeconomic and family vulnerability and unwanted pregnancy on prematurity occurred indirectly through inadequacy of prenatal care. The proposed methodology allowed using constructs, verifying the role of mediation by inadequacy of prenatal care, and identifying the variables' direct and indirect effects on the outcome preterm birth.

Dendritic cells (DC) are professional antigen presenting cells, uniquely able to induce naïve T cell activation and effector differentiation. They are, likewise, involved in the induction and maintenance of immune tolerance in homeostatic conditions. Their phenotypic and functional heterogeneity points to their great plasticity and ability to modulate, according to their microenvironment, the acquired immune response and, at the same time, makes their precise classification complex and frequently subject to reviews and improvement. This review will present general aspects of the DC physiology and classification and will address their potential and actual uses in the management of human disease, more specifically cancer, as therapeutic and monitoring tools. New combination treatments with the participation of DC will be also discussed.

Diabetes is one of the most concerning diseases in modern times. Despite considerable advances in therapeutic management, the prevalence of diabetes and its contribution to death and disability continue to be a major health problem. Diabetic vasculopathies are the leading cause of mortality and morbidity in diabetic patients. Its pathophysiology includes oxidative stress, advanced glycation end products, and a low-grade inflammatory state. Lately, actions of the innate immune system via Toll-like receptors (TLRs) have been suggested as a new insight in this field. TLRs are pattern recognition receptors activated by highly conserved structural motifs of exogenous or endogenous ligands. Heat-shock proteins (HSPs), normally known for their ability to protect cells during stressful conditions, when released from injured cells bind to TLR4 and trigger the release of pro-inflammatory cytokines in a MyD88-dependent pathway. This pathway had been investigated in pancreatic beta cells and skeletal muscle, but it has not yet been explored in the vascular system and deserves investigation. In this work, the interplay between TLR4 and HSP70 in the vasculature during diabetes is reviewed and discussed. The current literature and preliminary results from our laboratory led us to hypothesize that hyperglycemia-associated HSP70 plays an important role in the pathophysiology of diabetic vasculopathies via the TLR4 pathway and might be a new target for therapeutic intervention., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The iron(II) complexes of two structural isomers of 2-(1 H-imidazol-2-yl)diazine reveal how ligand design can be a successful strategy to control the electronic and magnetic properties of complexes by fine-tuning their ligand field. The two isomers only differ in the position of a single diazinic nitrogen atom, having either a pyrazine (Z) or a pyrimidine (M) moiety. However, [Fe(M) 3 ](ClO 4 ) 2 is a spin-crossover complex with a spin transition at 241 K, whereas [Fe(Z) 3 ](ClO 4 ) 2 has a stable magnetic behavior between 2 and 300 K. This is corroborated by temperature-dependent Mössbauer spectra showing the presence of a quintet and a singlet state in equilibrium. The temperature-dependent single-crystal X-ray diffraction results relate the spin-crossover observed in [Fe(M) 3 ](ClO 4 ) 2 to changes in the bond distances and angles of the coordination sphere of iron(II), hinting at a stronger σ donation of ligand Z in comparison to ligand M. The UV/vis spectra of both complexes are solved by means of the multiconfigurational wave-function-based method CASPT2 and confirm their different spin multiplicities at room temperature, as observed in the Mössbauer spectra. Calculations show larger stabilization of the singlet state in [Fe(Z) 3 ] 2+ than in [Fe(M) 3 ] 2+ , stemming from the slightly stronger ligand field of the former (506 cm -1 in the singlet). This relatively weak effect is indeed capable of changing the spin multiplicity of the complexes and causes the appearance of the spin transition in the M complex.