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Abstract Background In malaria infection, apoptosis acts as an important immunomodulatory mechanism that leads to the elimination of parasitized cells, thus reducing the parasite density and controlling immune cell populations. Here, it was investigated the association of INDEL variants in apoptotic genes—rs10562972 (FAS), rs4197 (FADD), rs3834129 and rs59308963 (CASP8), rs61079693 (CASP9), rs4647655 (CASP3), rs11269260 (BCL-2), and rs17880560 (TP53)—and the influence of genetic ancestry with susceptibility to malaria and parasite density in an admixed population from the Brazilian Amazon. Methods Total DNA was extracted from 126 malaria patients and 101 uninfected individuals for investigation of genetic ancestries and genotypic distribution of apoptosis-related variants by Multiplex PCR. Association analyses consisted of multivariate logistic regressions, considering the following comparisons: (i) DEL/DEL genotype vs. INS/DEL + INS/INS; and (ii) INS/INS vs. INS/DEL + DEL/DEL. Results Individuals infected by Plasmodium falciparum had significantly higher African ancestry proportions in comparison to uninfected controls, Plasmodium vivax, and mixed infections. The INS/INS genotype of rs3834129 (CASP8) seemed to increase the risk for P. falciparum infection (P = 0.038; OR = 1.867; 95% CI 0.736–3.725), while the DEL/DEL genotype presented a significant protective effect against infection by P. falciparum (P = 0.049; OR = 0.446; 95% CI 0.185–0.944) and mixed infection (P = 0.026; OR = 0.545; 95% CI 0.281–0.996), and was associated with lower parasite density in P. falciparum malaria (P = 0.009; OR = 0.383; 95% CI 0.113–1.295). Additionally, the INS/INS genotype of rs10562972 (FAS) was more frequent among individuals infected with P. vivax compared to P. falciparum (P = 0.036; OR = 2.493; 95% CI 1.104–4.551), and the DEL/DEL genotype of rs17880560 (TP53) was significantly more present in patients with mono-infection by P. vivax than in individuals with mixed infection (P = 0.029; OR = 0.667; 95% CI 0.211–1.669). Conclusions In conclusion, variants in apoptosis genes are associated with malaria susceptibility and parasite density, indicating the role of apoptosis-related genetic profiles in immune responses against malaria infection.

Despite recent efforts to search for biomarkers for the pre-symptomatic diagnosis of Parkinson’s disease (PD), the presence of risk factors, prodromal signs, and family history still support the classification of individuals at risk for this disease. Human epidemiological studies are useful in this search but fail to provide causality. The study of well-known risk factors for PD in animal models can help elucidate mechanisms related to the disease’s etiology and contribute to future prevention or treatment approaches. This narrative review aims to discuss animal studies that investigated four of the main risk factors and/or prodromal signs related to PD: advanced age, male sex, sleep alterations, and depression. Different databases were used to search the studies, which were included based on their relevance to the topic. Although still in a reduced number, such studies are of great relevance in the search for evidence that leads to a possible early diagnosis and improvements in methods of prevention and treatment.

Abstract The effect of metabolic syndrome (MetS) and clusters of its components on central blood pressure (CBP) has not been well characterized. We aimed to describe the effect of MetS and clusters of its components on CBP in a large population and to identify whether this effect differs in men and women. We studied 15,609 volunteers (43% women) from 10 cohorts worldwide who participated in the Metabolic syndrome and Artery REsearch Consortium. MetS was defined according to the NCEP-ATP III criteria (GHTBW, glucose, high-density lipoprotein cholesterol, triglyceride, blood pressure, waist circumference). CBP was measured noninvasively and acquired from pulse wave analysis by applanation tonometry. MetS was associated with a 50% greater odds of having higher CSBP. After controlling for age, male sex, non HDL cholesterol, diabetes mellitus, and mean arterial pressure, only specific clusters of MetS components were associated with a higher CSBP; and some of them were significant in women but not in men. We identified “risky clusters” of MetS variables associated with high CSBP. Future studies are needed to confirm they identify subjects at high risk of accelerated arterial aging and, thus, need more intensive clinical management.

Parkinson’s disease (PD) is characterized by motor and non-motor signs, which are accompanied by progressive degeneration of dopaminergic neurons in the substantia nigra. Although the exact causes are unknown, evidence links this neuronal loss with neuroinflammation and oxidative stress. Repeated treatment with a low dose of reserpine—inhibitor of VMAT2—has been proposed as a progressive pharmacological model of PD. The aim of this study was to investigate whether this model replicates the neuroinflammation characteristic of this disease. Six-month-old Wistar rats received repeated subcutaneous injections of reserpine (0.1 mg/kg) or vehicle on alternate days. Animals were euthanized after 5, 10, or 15 injections, or 20 days after the 15th injection. Catalepsy tests (motor assessment) were conducted across treatment. Brains were collected at the end of each treatment period for immunohistochemical and RT-PCR analyzes. Reserpine induced a significant progressive increase in catalepsy duration. We also found decreased immunostaining for tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNpc) and increased GFAP + cells in the SNpc and dorsal striatum after 10 and 15 reserpine injections. Phenotyping microglial M1 and M2 markers showed increased number of CD11b + cells and percentage of CD11b + /iNOS + cells in reserpine-treated animals after 15 injections, which is compatible with tissue damage and production of cytotoxic factors. In addition, increased CD11b + /ArgI + cells were found 20 days after the last reserpine injection, together with an increment in IL-10 gene expression in the dorsal striatum, which is indicative of tissue repair or regeneration. Reserpine also induced increases in striatal interleukin TNF-alpha mRNA levels in early stages. In view of these results, we conclude that reserpine-induced progressive parkinsonism model leads to neuroinflammation in regions involved in the pathophysiology of PD, which is reversed 20 days after the last injection. These findings reveal that withdrawal period, together with the shift of microglial phenotypes from the pro-inflammatory to the anti-inflammatory stage, may be important for the study of the mechanisms involved in reversing this condition, with potential clinical applicability.

Abstract Background The use of thermotolerant yeast strains can improve the efficiency of ethanol fermentation, allowing fermentation to occur at temperatures higher than 40 °C. This characteristic could benefit traditional bio-ethanol production and allow simultaneous saccharification and fermentation (SSF) of starch or lignocellulosic biomass. Results We identified and characterized the physiology of a new thermotolerant strain (LBGA-01) able to ferment at 40 °C, which is more resistant to stressors as sucrose, furfural and ethanol than CAT-1 industrial strain. Furthermore, this strain showed similar CAT-1 resistance to acetic acid and lactic acid, and it was also able to change the pattern of genes involved in sucrose assimilation (SUC2 and AGT1). Genes related to the production of proteins involved in secondary products of fermentation were also differentially regulated at 40 °C, with reduced expression of genes involved in the formation of glycerol (GPD2), acetate (ALD6 and ALD4), and acetyl-coenzyme A synthetase 2 (ACS2). Fermentation tests using chemostats showed that LBGA-01 had an excellent performance in ethanol production in high temperature. Conclusion The thermotolerant LBGA-01 strain modulates the production of key genes, changing metabolic pathways during high-temperature fermentation, and increasing its resistance to high concentration of ethanol, sugar, lactic acid, acetic acid, and furfural. Results indicate that this strain can be used to improve first- and second-generation ethanol production in Brazil.

Abstract Riparian zones are intrinsically sensitive habitats to anthropogenic disturbances. Knowledge about how riparian soil attributes respond to anthropogenic changes remains limited. This information would allow the prediction of degradation and contamination soil scenarios that threaten water quality for supply. Here, we studied the impact on soil quality and concentration that potentially toxic elements caused through changes in land use in riparian soils in northeastern Brazil. A total of thirty riparian soil composite samples were collected from areas with different land use and evaluated for physical and chemical attributes, in addition to potentially toxic elements (Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn). The results showed that replacing the natural vegetation in the riparian zone led to degradation gradient: pasture < agricultural < urban < industrial use. Soil attributes were sensitive in distinguishing the degree of degradation of each land use. Concentrations of the potentially toxic elements Cd and Zn are above the background soil concentrations and may pose a risk to the environment and human health. Our data can be helpful to understand better the complex relationship between land use and environmental impacts in riparian zones in northeastern Brazil and similar settings worldwide.

Abstract Anurans are considered one of the most threatened animal groups in the world. Agricultural activities are related to water pollution and contamination, which affects biphasic organisms such as amphibians. Brazilian soybean cultivation covers about 36 million hectares and encompasses many remaining ponds used as breeding sites for amphibians. In this study, we evaluated richness, abundance and composition of the anuran communities in ponds with different levels of association with soybean cultivation. A total of 18 anuran species were recorded with an abundance of 421 collected tadpoles and 1230 adult males on average. Ponds presented in soybean plantations were distinct from those adjacent to plantations regarding water properties and tadpole richness and abundance, as well as composition of tadpoles and adults. Ponds inserted in plantations had communities with lower diversity and abundance. One explanation for these results is likely the detrimental effect of soybean management, which suggests that this decrease is a result of community changes. This serves as an alert about the importance of buffer areas around plantations and the use of adequate techniques for pesticide application.

Parkinson’s disease (PD) is the second most common neurodegenerative disease. The main symptoms are motor signs such as resting tremor and difficulty in initializing movements. Non-motor alterations, such as cognitive deficits, can precede the motor symptoms. PD is more frequent in men than women. The mechanisms related to this difference are not completely understood. There is evidence that females present distinct characteristics in dopaminergic function compared to males. While the severity of motor impairments is often compared between sexes, little is known about sex differences in the prodromal stage. Most animal models of PD present acute severe motor impairment, which precludes the study of non-motor symptoms. Our research group have proposed an adaptation of the classic reserpine protocol, using low doses in a chronic treatment. This method allows the observation of progressive motor impairment as well as premotor deficits. Here we investigate possible behavioral and neuronal sex differences in the effects of the repeated treatment with a low dose of reserpine in rats. Male and female Wistar rats received 10–15 injections of reserpine (0.1 mg/kg) or vehicle, on alternate days. We followed-up the estrous cycle phases and conducted motor and cognitive assessments (catalepsy, open field, oral movements and object recognition tests). The euthanasia occurred 48 h after the 10th or 15th injections, with the collection of blood for the quantification of sex hormones and brains for tyrosine hydroxylase (TH) immunohistochemistry in the substantia nigra pars compact (SNpc). Reserpine induced progressive catalepsy, involuntary oral movements and cognitive deficits in male rats. The behavioral effects of reserpine were attenuated (motor) or absent (cognitive) in females. Reserpine decreased TH immunoreactivity in males, but not in females. Estrogen levels in females negatively correlated with catalepsy duration. Our findings show that females present a delay and/or a prevention in the reserpine-induced motor alterations in the progressive PD model, compatible with the lower prevalence of this disease in women. Further, females were protected from the deficit in object recognition at the prodromal stage. The absence of reserpine-induce decrease in TH immunoreactivity suggests that differences in dopaminergic function/plasticity are related to this protection in female sex.

Objective: To assess the procalcitonin protocol use and its impact on antibiotic therapy management of critically ill patients in the intensive care unit (ICU). Method: An observational descriptive and retrospective study conducted in an adult ICU with 28 beds from the Brazilian Unified Health System (SUS). Results: This present study observed a 78% (90/116) of PCT protocol adherence in the studied ICU. We observed a reduction in days of antibiotic treatment (DOT) going from 14 to 8,5 treatment-day duration (5.49 ± 2.2 days), impacting the overall antibiotic therapy cost for a decrease of 40.91%. Conclusion: The study revealed that PCT use was associated with substantial benefits, reducing hospital costs and days of exposure to antibiotic therapy applied to patients affected by infectious diseases in critical care settings.

Aim of the study: To adjust nonlinear Gompertz model to describe the body growth and feed intake (FI) of free-range chickens of the CPK (Color Plumé) strain, receiving different levels of digestible lysine (dig-Lys), from 21 to 77 days of age. Area of study: São Cristovão, Sergipe, Brazil. Material and methods: A total of 432 one-day-old unsexed chickens were used in the study. At 21 days of age, the birds were assigned to four treatments (0.85%; 0.97%; 1.09%; 1.21%) of dig-Lys, in a completely randomized design with four replicates, with 27 birds per experimental unit. The Gompertz model was used to estimate bird growth curves related to body weight (BW) and FI at each Lys level. Main results: The tests of comparison between the parameters of the Gompertz model for each Lys level showed that parameter A varied, while parameters B (0.0329) and C (45.819) did not differ significantly. In parameter A, the dig-Lys level of 0.97% provided the highest BW estimate at maturity and maximum BW at the inflection point. Research highlights: Use of non-linear models to predict nutritional requirements, helps farmers to optimize management decisions and, thus, maximize their profit. According to Gompertz model, it was possible to infer that the inclusion of 0.97% dig-Lys in the diet of mixed batches of free-range chickens of the CPK strain meets their nutritional requirements.

Malaria is a human parasitic disease distributed in many tropical countries and caused by various Plasmodium species. Plasmodium vivax has the largest geographical distribution of the Plasmodium species and is predominant in the Americas, including Brazil. Only a small number of P. vivax vaccine formulations have successfully reached clinical trials relative to their P. falciparum counterparts. One of the candidate antigens for a blood-stage P. vivax vaccine is apical membrane antigen 1 (PvAMA-1). Due to the worldwide distribution of Plasmodium parasites, a high degree of variability has been detected in this antigen sequence, representing a considerable challenge to the development of a universal vaccine against malaria. In this study, we evaluated how PvAMA-1 polymorphisms influence vaccine-derived immune responses in P. vivax malaria. To this end, we expressed 9 recombinant protein representatives of different PvAMA-1 allelic variants in the yeast Pichia pastoris: Belem, Chesson I, Sal-1, Indonesia XIX, SK0814, TC103, PNG_05_ESP, PNG_62_MU, and PNG_68_MAS. After protein expression and purification, we evaluated the breadth of the immune responses derived from malaria-exposed individuals from the Amazon region. From 611 serum samples of malaria-exposed individuals, 53.68% of them reacted against the PvAMA-1 Belem through ELISA. Positive samples were further tested against recombinant proteins representing the other PvAMA-1 allelic variants. Whereas Sal-1, Chesson I and SK0814 variants were highly recognized by tested serum samples, Indonesia XIX, TC103, PNG_05_ESP, PNG_62_MU, and PNG_68_MAS were only slightly recognized. Moreover, polyclonal sera derived from C57BL/6 mice immunized with the PvAMA-1 Belem protein predominantly recognized Belem, Sal-1, Chesson I, SK0814, and Indonesia XIX through ELISA. Last, ELISA-based competition assays demonstrated that a previous interaction between anti-Belem polyclonal serum and Sal-1, Chesson I, SK0814, or Indonesia XIX proteins could further inhibit antibody binding to the Belem variant. Our human and mouse data suggest the presence of common epitopes or cross-reactivity between Belem, Sal-1, Chesson I, and SK0814 variants. Although the PvAMA-1 Belem variant induces strain-transcendent antibodies, PvAMA-1 variants from Thailand and Papua New Guinea may need to be included in a universal vaccine formulation to achieve protection against P. vivax malaria.

The objective of this study was to evaluate the effects of biocholine powder (BP) added to the concentrate of ewe lambs on growth, rumen fermentation, antioxidant status, and metabolism. Forty-eight Lacaune lambs were divided 3 treatments: T0, T4, and T8, representing 0, 4, and 8 g of BP per animal/day added to the concentrate, respectively. The T4 and T8 lambs had greater average daily gain from d 0–75 (0.22, 0.25, and 0.26 kg/d for T0, T4 and T8, respectively). T4 and T8 lambs had higher methylene blue test results (indicating microbiological activity), and the higher effects were detected for T8 lambs. The BP in lamb’s diet increased the ruminal concentration of propionate (T4 and T8). The T8 lambs had greater serum activity of superoxide dismutase and glutathione transferase, and lower reactive oxygen species levels. We conclude that BP is a biotechnological additive with high nutritional potential.

[This corrects the article DOI: 10.1371/journal.pone.0113357.].

Background To estimate the strength of the cross‐sectional and longitudinal association between arterial stiffness, measured by pulse‐wave velocity, and cognitive function, distinguishing between global cognition, executive functions, and memory and to examine the influence of demographic, clinical, and assessment characteristics on this relationship. Methods and Results Systematic review of MEDLINE (via PubMed), Scopus, and WOS databases from their inception to March 2019, to identify cross‐sectional and longitudinal studies on the association between pulse‐wave velocity and cognitive domains (ie, global cognition, executive functions, and memory) among adult population. A total of 29 cross‐sectional and 9 longitudinal studies support the negative relationship between arterial stiffness and cognitive function, including global cognition, executive function, and memory. Demographic, clinical, and assessment characteristics did not substantially modify the strength of this association. Conclusions Evidence reveals a negative association between arterial stiffness, measured using pulse‐wave velocity, and cognition, specifically executive function, memory, and global cognition. This association seems to be independent of demographic, clinical, and assessment characteristics. These results accumulate evidence supporting that pulse‐wave velocity assessment could be a useful tool to identify individuals at high risk of cognitive decline or early stages of cognitive decline, to implement interventions aimed at slowing the progression to dementia.

Abstract Background Malaria can be transmitted by blood transfusion through donations collected from asymptomatic or parasitic donors. The parasites are released into the bloodstream during its life cycle and will therefore be present in donated blood by infected individuals. All cases of transfusion-transmitted malaria (TTM) notified since 2005 in Brazil were fatal. A good screening tool for Plasmodium spp. detection in blood units must have a high detection threshold, and the prevention of TTM relies entirely on the exclusion of potentially infected donors. However, in Brazilian blood banks, the screening test relies on blood thick smears examination. Methods The molecular diagnostic based on mitochondrial DNA (mtDNA) using real time PCR (mt-qPCR) was improved to detect Plasmodium falciparum, Plasmodium vivax, and standardized for use in Plasmodium malariae. The analytic sensitivity of this mt-qPCR methodology was performed using a sample of P. vivax. Results The mt-qPCR was highly efficient, and the analytic sensitivity for P. vivax was determined (0.000006 parasites/µL). This method was tested to detect P. vivax and P. falciparum in individuals from two malaria-endemic areas in Brazil, Amazon region (Pará and Rondônia states), the samples were collected in 10 reference units of two blood banks (Pará/nine cities and Rondônia/Porto Velho), and parasites mtDNA were detected in 10 of 2224 potential blood donors (0.45%). In all 10 positive samples, only P. vivax was detected. Conclusion Molecular diagnostic using mt-qPCR was effective in revealing infected potential donors with good perspectives to be applied as screening routine of asymptomatic carriers for preventing transfusion-transmitted malaria in blood banks.

Helicoverpa armigera (Hübner) is one of the most important agricultural pests in the world. This historically Old World species was first reported in Brazil in 2013 and has since spread throughout much of South America and into the Caribbean. Throughout North America, H. armigera surveys are ongoing to detect any incursions. Each trap is capable of capturing hundreds of native Helicoverpa zea (Boddie). The two species cannot be separated without genitalic dissection or molecular methods. A ddPCR assay is currently used to screen large trap samples, but this equipment is relatively uncommon and expensive. Here, we optimized a newly designed assay for accurate and repeatable detection of H. armigera in bulk samples across both ddPCR and less costly, and more common, real-time PCR methods. Improvements over previously designed assays were sought through multiple means. Our results suggest bulk real-time PCR assays can be improved through changes in DNA extraction and purification, so that real-time PCR can be substituted for ddPCR in screening projects. While ddPCR remains a more sensitive method for detection of H. armigera in bulk samples, the improvements in assay design, DNA extraction, and purification presented here also enhance assay performance over previous protocols.

Background: Pulse Wave Velocity (PWV) is a measure of arterial stiffness and vascular aging and an important parameter for cardiovascular risk stratification. A previous study showed high prevalence rates of early vascular aging in an adult population from the North of Portugal. The aim of this study was to characterize children from the same region regarding PWV and its relationship with central adiposity indices and blood pressure. Methods: A convenience sample of 285 children aged 10–14 years attending a Northern Portuguese school was used. PWV, height, weight, body mass index (BMI), waist circumference e blood pressure (BP) were measured. Collected data was distributed by gender, age and height specific percentiles. Results: Mean PWV values were 5.4 ± 1.0 for males and 5.1 ± 0.7 for females. We only found statistically significant differences between males and females PWV in the 13’ years old group (p = 0.02). 27.4% of the children (N = 78) had PWV ≥ 90th percentile, 64.1% of which were males (N = 50) and 15.3% (N = 12) were overweight/obese. PWV was significantly higher in children with systolic BP ≥ 90th percentile (p = 0.004). No differences were found in PWV between overweight/obese (BMI ≥ 85th percentile) and healthy weight children. Conclusion: Our study found a high prevalence rate of elevated PWV in children. This is a concerning aspect, taking into account the highly recognized relationship of PWV and cardiovascular outcomes, indicating that healthy policy measures need to be implemented early in life. Future research is needed to establish PWV reference percentile curves specific for Portuguese children.

Background: Arterial stiffening measured by Pulse Wave Velocity (PWV) predicts cardiovascular events and mortality in adults. It advances with age and seems accelerated in children with certain disease conditions such as chronic kidney disease or diabetes. The aim of this study was to determine factors that influence PWV in children. Methods: PWV was captured in 285 children aged 10–14 years attending a Portuguese school. The effects of sex, age, height, weight, body mass index, waist circumference, blood pressure, heart rate and sodium excretion in 24-h urinary samples in PWV were tested. Results: PWV correlated positively with age, height, systolic blood pressure, diastolic blood pressure and heart rate in males and females (p < 0.05) and with weight in males (p < 0.05). Major predictors for PWV in a multivariate regression analysis were gender, height, weight, diastolic blood pressure, heart rate and body mass index. Conclusion: Our study found several determinants of PWV in children, some of them modifiable and interfering with cardiovascular outcomes. Future research may provide clarity to the association between PWV in children and cardiovascular events in adulthood.

Background Chronic deposits of advanced glycation end products produced by enzymatic glycation have been suggested as predictors of atherosclerotic‐related disorders. This study aimed to estimate the relationship between advanced glycation end products indicated by skin autofluorescence levels and the risk of cardiovascular and all‐cause mortality based on data from observational studies. Methods and Results We systematically searched Medline, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the Web of Science databases from their inceptions until November 2017 for observational studies addressing the association of advanced glycation end products by skin autofluorescence levels with cardiovascular and all‐cause mortality. The DerSimonian and Laird random‐effects method was used to compute pooled estimates of hazard ratios and their respective 95% confidence intervals for the risk of cardiovascular and all‐cause mortality associated with levels of advanced glycation end products by skin autofluorescence. Ten published studies were included in the systematic review and meta‐analysis. Higher skin autofluorescence levels were significantly associated with a higher pooled risk estimate for cardiovascular mortality (hazard ratio: 2.06; 95% confidence interval, 1.58–2.67), which might not be important to moderate heterogeneity (I2=34.7%; P=0.163), and for all‐cause mortality (hazard ratio: 1.91; 95% confidence interval, 1.42–2.56) with substantial heterogeneity (I2=60.8%; P=0.0.18). Conclusions Our data suggest that skin autofluorescence levels could be considered predictors of all‐cause mortality and cardiovascular mortality in patients at high and very high risk.