Magnetized vermiculite as a tool for the treatment of produced water generated by oil companies: Effects on aquatic organisms before and after treatment.

Produced water (PW) generated by oil companies is a highly impacting waste that contains chemicals such as metals and organic and inorganic compounds. Given its polluting potential, PW requires effective treatment before being discharged into the environment. Conventional treatments have limited efficiency in removing PW toxicity, so alternative approaches must be developed and standardized. In this context, treatment with adsorbent materials like magnetized vermiculite (VMT-mag) is highlighted. This work aimed to evaluate the efficiency of treatment with VMT-mag in reducing PW toxicity to aquatic biota. For this purpose, three aquatic species (the midge Chironomus riparius, the planarian Girardia tigrina, and the crustacean Daphnia magna) were exposed to untreated PW and to PW treated with VMT-mag at laboratory conditions. The assessed endpoints included mortality, growth, emergence, and developmental time of C. riparius; mortality, locomotion, feeding, and head regeneration of G. tigrina; and intrinsic population growth rate (r) and reproductive output of D. magna. The results showed that all the species exposed to raw PW were impaired: C. riparius had delayed development, G. tigrina had reduced locomotor activity and delayed head regeneration, and D. magna had reduced reproduction and delayed intrinsic population growth rate (r). Most of the analyzed parameters showed that treatment with VMT-mag diminished PW toxicity. Therefore, using VMT-mag to treat PW may be the key to reducing the PW effects on aquatic organisms.

Fine cassava fibre utilization as a dietary fibre source for dogs: Effects on kibble characteristics, diet digestibility and palatability, faecal metabolites and microbiota.

The objective was to evaluate through three experiments the effects of a fine cassava fibre (CA: 106 µm) on kibble characteristics, coefficients of total tract apparent digestibility (CTTAD) of macronutrients, diet palatability and faecal metabolites and microbiota of dogs. Dietary treatments consisted of a control diet (CO), without an added fibre source and with 4.3% total dietary fibre (TDF), and a diet with 9.6% CA (106 µm), with 8.4% TDF. Experiment I evaluated the physical characteristics of the kibbles. The palatability test was evaluated in experiment II, which compared the diets CO versus CA. In experiment III, 12 adult dogs were randomly assigned to one of the two dietary treatments for 15 days, totalling six replicates/treatment, to assess the CTTAD of macronutrients; faecal characteristics, faecal metabolites and microbiota. The expansion index, kibble size and friability of diets with CA were higher than the CO (p < 0.05). Additionally, the CA diet presented higher palatability than the CO (p < 0.05) but did not affect CTTAD except for those of fibre (p > 0.05). Moreover, a greater faecal concentration of acetate, butyrate and total short-chain fatty acids (SCFA) and a lower faecal concentration of phenol, indole and isobutyrate were observed in dogs fed the CA diet (p < 0.05). Dogs fed with the CA diet presented a greater bacterial diversity and richness and a greater abundance of genera considered to be beneficial for gut health, such as Blautia, Faecalibacterium and Fusobacterium when compared to the CO group (p < 0.05). The inclusion of 9.6% of a fine CA improves the expansion of kibbles and diet palatability without affecting most of the CTTAD of nutrients. Besides, it improves the production of some SCFA and modulates the faecal microbiota of dogs.

Evaluation of postprandial glycemic response in rats (Wistar) fed with different starch sources.

The consumption of readily digestible starch sources, such as corn, can negatively impact endocrine disorders related to hyperglycaemia in predisposing animals. In this sense, starch sources containing slowly digestible and resistant fractions can assist glycemic control. The present study analyzed the postprandial glycemic response and blood variables of rats fed with four extruded diets containing corn, brown rice, sweet potato and pea as the main starch source. Thirty-two male Wistar rats (90 days old) were divided into groups of eight animals each. The rats received one of the experimental diets for 30 days according to a completely randomised design. The glycemia was measured on the 29th and 30th days. The glycemia measured on the 29th day was analyzed at 0, 30, 60, 120 and 240 min after oral administration of 50% glucose solution. On the 30th day, the same protocol was repeated after providing 3 g of the experimental diet for each animal to obtain the glycemic curve. After the euthanasia on the 30th day, 7 ml of blood was collected via cardiac puncture for glycated haemoglobin (HBA1c), triglycerides, cholesterol, and aspartate and alanine aminotransferases analysis. Diets with pea and sweet potato provided lower glycemic index, average and maximum glycemia, and glycemic increment in relation to the other starch sources (p < 0.05). Animals fed with the corn diet had higher serum concentrations of triglycerides and HBA1c than the other treatments (p < 0.05). Results demonstrated that pea and sweet potato are interesting starch sources for the control of metabolic disorders related to glycemia.

Neck Strength Evaluated With Fixed and Portable Dynamometers in Asymptomatic Individuals: Correlation, Concurrent Validity, and Agreement.

OBJECTIVE: The purpose of this study was to assess the correlation, concurrent validity, and agreement between the isometric cervical force measurements obtained with fixed and portable dynamometers in asymptomatic individuals. METHODS: Fifty asymptomatic individuals performed 3 maximal isometric contractions for flexion, extension, and lateral flexion of the cervical spine using fixed and portable dynamometers. The correlation and concurrent validity for the measurements of the portable and fixed dynamometers were analyzed using Spearman's correlation coefficient and the intraclass correlation coefficient (ICC), respectively. The agreement between the force values of the portable and fixed dynamometers was measured using the Bland-Altman method. RESULTS: Isometric cervical force measurements obtained with the fixed dynamometer and portable dynamometer showed a moderately to highly significant correlation for flexion (rs = 0.74), extension (rs = 0.82), right lateral flexion (rs = 0.74), and left lateral flexion (rs = 0.68). The concurrent validity was moderate to good for all measurements (ICC2,3 = 0.67-0.80). The fixed and portable dynamometers did not agree, with a significant mean difference between the methods of 2.8 kgf (95% confidence interval [CI], 2.1-3.4 kgf) for cervical flexion, 5.3 kgf (95% CI, 4.2-6.4 kgf) for extension, and 9.1 kgf (95% CI, 0.4-2.1 kgf) for left lateral flexion. The limits of agreement were broad for all movements, with errors that varied between 61% and 77% of the mean force obtained with the fixed dynamometer. CONCLUSION: The neck strength measurements obtained with the fixed and portable dynamometers demonstrated high to moderate correlation and had moderate to good comparability for asymptomatic participants. However, they did not agree in that the 2 methods did not provide equivalent measurements, and, therefore, based on these findings, the same equipment should always be used when reassessing an individual.

In defense of leader misconduct: the use of neutralization techniques by ingroup members.

The current study is an initial effort to investigate the value of neutralization theory to understand how, by what method, to what degree, and in what condition ingroup members defend their leader against charges of misconduct. We propose that ingroup members use neutralizing techniques to defend their leaders in the same way they would defend themselves. After exploring the underlying social identity theory driving the use of leader defense, we test our proposition by analyzing the Trump-Ukraine Impeachment Inquiry Republican Staff Report. Using content analysis, we determine the presence of neutralization techniques and classify those instances into specific neutralization categories proposed in the literature. Using a post-hoc analysis, we then explore under what conditions ingroup members use specific neutralization techniques in defense of an ingroup leader. Our study extends prior theory and research by examining the use of neutralization techniques in defense of an ingroup leader's alleged misconduct.

Predictors of parental satisfaction with the pediatric ophthalmology care in a Brazilian hospital.

The purpose of this cross-sectional study was to assess the satisfaction of parents of visually impaired children with the pediatric ophthalmology care in a Brazilian hospital and to associate parental satisfaction with predictor variables. The study enrolled children with a binocular and monocular visual impairment aged between 4 and 17 years from a single site in Brazil between June 2019 and May 2020. Parents or legal guardians answered the Brazilian version of the Pediatric Quality of Life InventoryTM (PedsQLTM 3.0) Healthcare Satisfaction Generic - Parents. Linear regression analysis was used to investigate the association between the PedsQL scores and predictor variables. The sample included 82 children and their respective parents. The mean PedsQL score was 90.3 ± 6.6 (out of 100). In the univariate model, child female sex (p = 0.056), child older age (p = 0.078), better eye visual acuity (VA; p = 0.016), and worse eye VA (p = 0.008) were significantly associated with higher scores. The multivariate estimates identified the worse eye VA (p = 0.034) as a predictor of parental satisfaction. In summary, parents' satisfaction with this pediatric ophthalmology care was high. Nevertheless, a continuous evaluation is warranted to keep up with parents' expectations and plan for possible improvements in clinical practice.

Effects of two dietary fiber levels on nutrient digestibility and intestinal fermentation products in captive brown howler monkeys (Alouatta guariba).

Herbivorous primates present a selective consumption profile and morphological adaptations to use the fibrous fraction of their diets. Brown howler monkeys (Alouatta guariba) are generalist herbivores; however, when kept under human care, they usually receive diets rich in fruits and with insufficient amounts of fiber. Thus, the objective of this study was to evaluate the effects of two levels of neutral detergent fiber (NDF) in howlers on apparent total tract digestibility coefficients (ATTDC), fecal consistency, and intestinal fermentation products. A group of 26 adult howler monkeys, 13 males and 13 females, were fed two diets formulated to have 33% or 40% NDF for 11 days, according to a randomized block design (N = 26). The block factor was the enclosures with one, two, or three individuals (each enclosure corresponded to an experimental unit), totaling in eight replicates per treatment. There were no differences in dry matter and nutrients intake between treatments (p > 0.05). The diet with 33% NDF resulted in higher (p < 0.05) ATTDC of crude protein and crude energy. However, lower fecal concentrations of short-chain fatty acids (SCFA) and dry matter were observed in the treatment with 33% NDF in contrast to the 40% NDF group (p < 0.05). We recommend the inclusion of higher fiber levels (40% NDF) in the diet of howler monkeys since there is evidence of greater production of SCFA and improvement in fecal consistency.

Airway Resistance and Respiratory Compliance in Children with Acute Viral Bronchiolitis Requiring Mechanical Ventilation Support.

BACKGROUND: Acute viral bronchiolitis (AVB) is a very frequent disease that affects the lower airways of young children increasing the inspiratory and expiratory resistance in variable degree as well as reducing the pulmonary compliance. It would be desirable to know whether these variables are associated with the outcome. OBJECTIVES: To evaluate the respiratory mechanics in infants with AVB requiring mechanical ventilation (MV) support and to evaluate if respiratory mechanics predict outcomes in children with AVB supported on MV. To evaluate the respiratory mechanics in infants with AVB submitted to MV. MATERIALS AND METHODS: A prospective observational study was conducted in two pediatric intensive care units (PICUs) between February 2016 and March 2017. Included were infants (1 month to 1 year old) admitted with AVB and requiring MV for >48 hours. Auto-PEEP, dynamic compliance (Cdyn), static compliance (Cstat), expiratory resistance (ExRes), and inspiratory resistance (InRes) were evaluated once daily on the second and third day of MV. RESULTS: A total of 64 infants (median age of 2.8 months and a mean weight of 4.8 ± 1.7 kg) were evaluated. A mean positive inspiratory pressure (PIP) of 31.5 ± 5.2 cmH2O, positive end-expiratory pressure (PEEP) of 5.5 ± 1.4 cmH2O, resulting in a mean airway pressure (MAP) of 12.5 ± 2.2 cmH2O and delta pressure of 22.5 ± 4.4 cmH2O without difference between the two hospitals. Measurements of respiratory mechanics showed high values of InRes and ExRes (median 142 [IQ25-75 106-180] cmH2O/L/s and 158 [IQ25-75 130-195.3] cmH2O/L/s, respectively), accompanied by decreased Cdyn and Cstat (0.46 ± 0.19 and 0.81 ± 0.25 mL/kg/cmH2O, respectively). None of the variables was associated with mortality, length of MV, or length of PICU stay. CONCLUSION: Infants with AVB requiring MV support present very high InRes and ExRes values. These findings might be the reason for the aggressive ventilatory parameters, especially PIP, required to ventilate this group of children with lower airway obstruction. CLINICAL SIGNIFICANCE: Monitoring respiratory mechanics could represent a useful tool to guide the ventilatory strategy to be adopted in patients with AVB. HOW TO CITE THIS ARTICLE: Andreolio C, Piva JP, Bruno F, da Rocha TS, Garcia PCR. Airway Resistance and Respiratory Compliance in Children with Acute Viral Bronchiolitis Requiring Mechanical Ventilation Support. Indian J Crit Care Med 2021;25(1):88-93.

Growth regulation of bermudagrass (Cynodon dactylon) and zoysiagrass (Zoysia japonica) with glyphosate.

Glyphosate can generate positive effects on turfgrass maintenance as a form of growth control by decreasing the expenses associated with mowing. However, there is little information about the effects of this herbicide on turfgrasses. This study aimed to evaluate the response of bermudagrass and zoysiagrass to the herbicide glyphosate as a growth regulator. Two studies were performed in a greenhouse and repeated at different times. The treatments involved application of glyphosate at 10 different rates (0, 5.625, 11.25, 22.5, 45, 90, 180, 360, 720, and 1.440 g ae ha-1) with four replicates. Evaluations of green cover by digital analysis, injury, and plant height were performed at 7, 14, 21, and 28 days after application, and shoot dry matter of clippings was determined for the last evaluation period. Bermudagrass and zoysiagrass presented variedtolerance to glyphosate toxicity. Overall, the digital analysis showed that green content was negatively influenced by the increase in visual injury caused by glyphosate application. Moreover, increasing the glyphosate rate decreased plant height and shoot dry matter in both turfgrasses. Glyphosate application rates up to 45 g ae ha-1 for bermudagrass and 90 g ae ha-1 for zoysiagrass decreased plant growth without affecting the factors analyzed in this study.

Evidence for an interrelated cluster of Hallucinatory experiences in the general population: an incidence study.

BACKGROUND: Although hallucinations have been studied in terms of prevalence and its associations with psychopathology and functional impairment, very little is known about sensory modalities other than auditory (i.e. haptic, visual and olfactory), as well the incidence of hallucinations, factors predicting incidence and subsequent course. METHODS: We examined the incidence, course and risk factors of hallucinatory experiences across different modalities in two unique prospective general population cohorts in the same country using similar methodology and with three interview waves, one over the period 1996-1999 (NEMESIS) and one over the period 2007-2015 (NEMESIS-2). RESULTS: In NEMESIS-2, the yearly incidence of self-reported visual hallucinations was highest (0.33%), followed by haptic hallucinations (0.31%), auditory hallucinations (0.26%) and olfactory hallucinations (0.23%). Rates in NEMESIS-1 were similar (respectively: 0.35%, 0.26%, 0.23%, 0.22%). The incidence of clinician-confirmed hallucinations was approximately 60% of the self-reported rate. The persistence rate of incident hallucinations was around 20-30%, increasing to 40-50% for prevalent hallucinations. Incident hallucinations in one modality were very strongly associated with occurrence in another modality (median OR = 59) and all modalities were strongly associated with delusional ideation (median OR = 21). Modalities were approximately equally strongly associated with the presence of any mental disorder (median OR = 4), functioning, indicators of help-seeking and established environmental risk factors for psychotic disorder. CONCLUSIONS: Hallucinations across different modalities are a clinically relevant feature of non-psychotic disorders and need to be studied in relation to each other and in relation to delusional ideation, as all appear to have a common underlying mechanism.

UCP2, IL18, and miR-133a-3p are dysregulated in subcutaneous adipose tissue of patients with obesity.

The aim of this study was to compare the expression of UCP2, NLRP3, IL1B, IL18, and miR-133a-3p in subcutaneous adipose tissue (SAT) of 61 patients divided according to BMI: Group 1 (n = 8; BMI<25.0 kg/m2), Group 2 (n = 24; BMI 30.0-39.9 kg/m2), and Group 3 (n = 29; BMI≥40.0 kg/m2). SAT biopsies were obtained from individuals who underwent bariatric surgery or elective abdominal surgery. Gene expressions were quantified using qPCR. Bioinformatics analyses were employed to investigate target genes and pathways related to miR-133a-3p. UCP2 and miR-133a-3p expressions were decreased in SAT of Groups 2 and 3 while IL18 was increased compared to Group 1. NLRP3 and IL1B expressions did not differ between groups; however, NLRP3 was positively correlated with waist circumference and excess weight. Bioinformatics analysis demonstrated that UCP2 and NLRP3 are targets of miR-133a-3p. In conclusion, UCP2 and miR-133a-3p expressions are downregulated in patients with obesity, while IL18 is upregulated. NRLP3 is correlated with waist circumference and weight excess.

Limitation of nitrogen source facilitated the production of nonmeiotic recombinants in Aspergillus nidulans.

Aspergillus nidulans is a fungal model organism extensively used in genetic approaches. It may reproduce sexually and asexually, with a well-defined parasexual cycle. The current paper demonstrates that the limitation of nitrogen source facilitates the production of A. nidulans's nonmeiotic recombinants directly from heterokaryons, without the recovery of the diploid phase. Heterokaryons formed between master strains were inoculated in sodium nitrate-low (basal medium [BM]) and sodium nitrate-rich media (minimal medium [MM]). All mitotic segregants produced by the heterokaryons were tested for their mitotic stability in the presence of benomyl, the haploidizing agent. Only mitotically stable haploid segregants were selected for subsequent analysis. Phenotypic analyses of such haploids favored the characterization of nonmeiotic recombinants. As the number of such recombinants was higher in BM than in MM, nitrogen limitation may have facilitated the isolation of nonmeiotic recombinants from heterokaryons by stimulating nuclear fusion still inside the heterokaryotic mycelium as a survival strategy.

Sensors Using the Molecular Dynamics of Explosives in Carbon Nanotubes Under External Uniform Electric Fields.

Possessing a simulated sensor device to identify explosives is of extreme interest to the area of public security to fight against terrorism. In light of this, a carbon armchair nanotube was modeled under the action of an external, longitudinal and uniform electric field at an initial temperature of 1 mK simulation, causing the explosive molecules under analysis to rotate through the carbon nanotube, due to an evanescent effect generated from the action of an electric current and magnetic field induced in this system, and thus behaving as a selective temperature sensor and spinning radius for the molecules. For this, molecular dynamics was used to study the physicochemical properties of the molecules' interactions with a carbon nanotube. The following physical properties, as well as the kinetic, potential, and total energy were calculated for the 2,4,6-trinitrotoluene (TNT), triacetone triperoxide (TATP), hexogen (RDX), hexamethylene triperoxide diamine (HMTD), octogen (HMX) and pentaerythritol tetranitrate (PETN) explosives: thermodynamic conditions such as temperature; entropy variation; and distance between the molecules' center of mass from an armchair type carbon nanotube.

Circulating miRNAs in diabetic kidney disease: case-control study and in silico analyses.

AIMS: The aim of this study was to investigate a miRNA expression profile in type 1 diabetes mellitus (T1DM) patients with DKD (cases) or without this complication (controls). METHODS: Expression of 48 miRNAs was screened in plasma of 58 T1DM patients (23 controls, 18 with moderate DKD, and 17 with severe DKD) using TaqMan Low Density Array cards (Thermo Fisher Scientific). Then, five of the dysregulated miRNAs were selected for validation in an independent sample of 10 T1DM controls and 19 patients with DKD (10 with moderate DKD and 9 with severe DKD), using RT-qPCR. Bioinformatic analyses were performed to explore the putative target genes and biological pathways regulated by the validated miRNAs. RESULTS: Among the 48 miRNAs investigated in the screening analysis, 9 miRNAs were differentially expressed between DKD cases and T1DM controls. Among them, the five most dysregulated miRNAs were chosen for validation in an independent sample. In the validation sample, miR-21-3p and miR-378-3p were confirmed to be upregulated in patients with severe DKD, while miR-16-5p and miR-29a-3p were downregulated in this group compared to T1DM controls and patients with moderate DKD. MiR-503-3p expression was not validated. Bioinformatic analyses indicate that the four validated miRNAs regulate genes from PI3K/Akt, fluid shear stress and atherosclerosis, AGE-RAGE, TGF-ß1, and relaxin signaling pathways. CONCLUSIONS: Our study found four miRNAs differentially expressed in patients with severe DKD, providing significant information about the biological pathways in which they are involved.

Correlation between DNA/HSA-interactions and antimalarial activity of acridine derivatives: Proposing a possible mechanism of action.

Acridines are considered an important class of compounds due to their wide variety of biological activities. In this work, we synthesized four acridine derivatives (1-4) and evaluated their biological activity against the Plasmodium falciparum W2 line, as well as studied the interaction with ctDNA and HSA using spectroscopic techniques and molecular docking. The acridine derivative 2 (IC50 = 0.90 ±â€¯0.08 µM) was more effective against P. falciparum than primaquine (IC50 = 1.70 ±â€¯0.10 µM) and similar to amsacrine (IC50 = 0.80 ±â€¯0.10 µM). In the fluorescence and UV-vis assays, it was verified that the acridine derivatives interact with ctDNA and HSA leading to a non-fluorescent supramolecular complex formation. The non-covalent binding constants ranged from 2.09 to 7.76 × 103 M-1, indicating moderate interaction with ctDNA. Through experiments with KI, fluorescence contact energy transfer and competition assays were possible to characterize the main non-covalent binding mode of the acridines evaluated with ctDNA as intercalation. The binding constants obtained showed a high linear correlation with the IC50 values against the antimalarial activity, suggesting that DNA may be the main biological target of these molecules. Finally, HSA interaction studies were performed and all evaluated compounds bind to the site II of the protein. The less active compounds (1 and 3) presented the highest affinity to HSA, indicating that the interaction with carrier protein can affect the (bio)availability of these compounds to the biological target.

MicroRNAs and diabetic kidney disease: Systematic review and bioinformatic analysis.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Emerging evidence has suggested a role for miRNAs in the development of diabetic kidney disease (DKD), indicating that miRNAs may represent potential biomarkers of this disease. However, results are still inconclusive. Therefore, we performed a systematic review of the literature on the subject, followed by bioinformatic analysis. PubMed and EMBASE were searched to identify all studies that compared miRNA expressions between patients with DKD and diabetic patients without this complication or healthy subjects. MiRNA expressions were analyzed in kidney biopsies, urine/urinary exosomes or total blood/plasma/serum. MiRNAs consistently dysregulated in DKD patients were submitted to bioinformatic analysis to retrieve their putative target genes and identify potentially affected pathways under their regulation. As result, twenty-seven studies were included in the systematic review. Among 151 dysregulated miRNAs reported in these studies, 6 miRNAs were consistently dysregulated in DKD patients compared to controls: miR-21-5p, miR-29a-3p, miR-126-3p, miR-192-5p, miR-214-3p, and miR-342-3p. Bioinformatic analysis indicated that these 6 miRNAs are involved in pathways related to DKD pathogenesis, such as apoptosis, fibrosis, and extracellular matrix accumulation. In conclusion, six miRNAs seem to be dysregulated in patients with different stages of DKD, constituting potential biomarkers of this disease.

MicroRNA expression profile in plasma from type 1 diabetic patients: Case-control study and bioinformatic analysis.

AIMS: To investigate a miRNA expression profile in plasma of type 1 diabetes (T1DM) patients and control subjects and analyze the putative pathways involved. METHODS: Expressions of 48 miRNAs were analyzed in plasma of 33 T1DM patients and 26 age-and-gender-matched controls using Stem-loop RT-PreAmp PCR and TaqMan Low Density Arrays (Thermo Fisher Scientific). Five dysregulated miRNAs were then chosen for validation in an independent sample of 27 T1DM patients and 14 controls, using RT-qPCR. Bioinformatic analyses were performed to determine in which pathways these miRNAs are involved. RESULTS: Nine miRNAs were differentially expressed between recently-diagnosed T1DM patients (<5 years of diagnosis) and controls. No differences were observed between patients with ≥5 years of diagnosis and controls. After validation in an independent sample of T1DM patients, miR-103a-3p, miR-155-5p, miR-200a-3p, and miR-210-3p were confirmed as being upregulated in recently-diagnosed T1DM patients compared with controls or patients with ≥5 years of diagnosis. Moreover, miR-146a-5p was downregulated in recently-diagnosed T1DM patients compared with the other groups. These five miRNAs regulate several genes from innate immune system-, MAPK-, apoptosis-, insulin- and cancer-related pathways. CONCLUSION: Five miRNAs are dysregulated in recently-diagnosed T1DM patients and target several genes involved in pathways related to T1DM pathogenesis, thus representing potential T1DM biomarkers.

MicroRNA expression profiles and type 1 diabetes mellitus: systematic review and bioinformatic analysis.

Growing evidence indicates that microRNAs (miRNAs) have a key role in processes involved in type 1 diabetes mellitus (T1DM) pathogenesis, including immune system functions and beta-cell metabolism and death. Although dysregulated miRNA profiles have been identified in T1DM patients, results are inconclusive; with only few miRNAs being consistently dysregulated among studies. Thus, we performed a systematic review of the literature on the subject, followed by bioinformatic analysis, to point out which miRNAs are dysregulated in T1DM-related tissues and in which pathways they act. PubMed and EMBASE were searched to identify all studies that compared miRNA expressions between T1DM patients and non-diabetic controls. Search was completed in August, 2017. Those miRNAs consistently dysregulated in T1DM-related tissues were submitted to bioinformatic analysis, using six databases of miRNA-target gene interactions to retrieve their putative targets and identify potentially affected pathways under their regulation. Thirty-three studies were included in the systematic review: 19 of them reported miRNA expressions in human samples, 13 in murine models and one in both human and murine samples. Among 278 dysregulated miRNAs reported in these studies, 25.9% were reported in at least 2 studies; however, only 48 of them were analyzed in tissues directly related to T1DM pathogenesis (serum/plasma, pancreas and peripheral blood mononuclear cells (PBMCs)). Regarding circulating miRNAs, 11 were consistently dysregulated in T1DM patients compared to controls: miR-21-5p, miR-24-3p, miR-100-5p, miR-146a-5p, miR-148a-3p, miR-150-5p, miR-181a-5p, miR-210-5p, miR-342-3p, miR-375 and miR-1275. The bioinformatic analysis retrieved a total of 5867 validated and 2979 predicted miRNA-target interactions for human miRNAs. In functional enrichment analysis of miRNA target genes, 77 KEGG terms were enriched for more than one miRNA. These miRNAs are involved in pathways related to immune system function, cell survival, cell proliferation and insulin biosynthesis and secretion. In conclusion, eleven circulating miRNAs seem to be dysregulated in T1DM patients in different studies, being potential circulating biomarkers of this disease.

Platinum(ii)-chloroquine complexes are antimalarial agents against blood and liver stages by impairing mitochondrial function.

Chloroquine is an antimalarial agent with strong activity against the blood stage of Plasmodium infection, but with low activity against the parasite's liver stage. In addition, the resistance to chloroquine limits its clinical use. The discovery of new molecules possessing multistage activity and overcoming drug resistance is needed. One possible strategy to achieve this lies in combining antimalarial quinolones with the pharmacological effects of transition metals. We investigated the antimalarial activity of four platinum(ii) complexes composed of chloroquine and phosphine ligands, denoted as WV-90, WV-92, WV-93 and WV-94. In comparison with chloroquine, the complexes were less potent against the chloroquine-sensitive 3D7 strain but they were as active as chloroquine in inhibiting the chloroquine-resistant W2 strain of P. falciparum. Regarding selectivity, the complexes WV-90 and WV-93 displayed higher indexes. Unlike chloroquine, the complexes act as irreversible parasiticidal agents against trophozoites and the WV-93 complex displayed activity against the hepatic stage of P. berghei. The in vivo suppression activity against P. berghei in the Peters 4 day test displayed by the complexes was similar to that of chloroquine. However, the efficacy in an established P. berghei infection in the Thompson test was superior for the WV-93 complex compared to chloroquine. The complexes' antimalarial mechanism of action is initiated by inhibiting the hemozoin formation. While chloroquine efficiently inhibits hemozoin, parasites treated with the platinum complexes display residual hemozoin crystals. This is explained since the interaction of the platinum complexes with ferriprotoporphyrin is weaker than that of chloroquine. However, the complexes caused a loss of mitochondrial integrity and subsequent reduction in mitochondrial activity, and their effects on mitochondria were more pronounced than those in the chloroquine-treated parasites. The dual effect of the platinum complexes may explain their activity against the hemozoin-lacking parasites (hepatic stage), where chloroquine has no activity. Our findings indicate that the platinum(ii)-chloroquine complexes are multifunctional antimalarial compounds and reinforce the importance of metal complexes in antimalarial drug discovery.

GLIS3 rs7020673 and rs10758593 polymorphisms interact in the susceptibility for type 1 diabetes mellitus.

AIMS: The transcription factor Gli-similar 3 (GLIS3) plays a key role in the development and maintenance of pancreatic beta cells as well as in the regulation of Insulin gene expression in adults. Accordingly, genome-wide association studies identified GLIS3 as a susceptibility locus for type 1 diabetes mellitus (T1DM) and glucose metabolism traits. Therefore, the aim of this study was to replicate the association of the rs10758593 and rs7020673 single nucleotide polymorphisms (SNPs) in the GLIS3 gene with T1DM in a Brazilian population. METHODS: Frequencies of the rs7020673 (G/C) and rs10758593 (A/G) SNPs were analyzed in 503 T1DM patients (cases) and in 442 non-diabetic subjects (controls). Haplotypes constructed from the combination of these SNPs were inferred using a Bayesian statistical method. RESULTS: Genotype and allele frequencies of rs7020673 and rs10758593 SNPs did not differ significantly between case and control groups. However, the frequency of ≥3 minor alleles of the analyzed SNPs in haplotypes was higher in T1DM patients compared to non-diabetic subjects (6.2 vs. 1.6%; P = 0.001). The presence of ≥3 minor alleles remained independently associated with risk of T1DM after adjustment for T1DM high-risk HLA DR/DQ haplotypes, age and ethnicity (OR = 3.684 95% CI 1.220-11.124). Moreover, levels of glycated hemoglobin seem to be higher in T1DM patients with rs10758593 A/A genotype than patients carrying the G allele of this SNP (P = 0.038), although this association was not kept after Bonferroni correction. CONCLUSIONS: Our results indicate that individually the rs7020673 and rs10758593 SNPs are not significantly associated with T1DM but seem to interact in the predisposition for this disease.