Aggregation patterns of curcumin and piperine mixtures in different polar media.

This work reports a thorough molecular dynamics investigation on the aggregation patterns of curcumin and piperine in water, ethanol and a mixture of both solvents. The low solubility of curcumin in water results in a rapid formation of very stable dimers for both keto and enol tautomers. In agreement with a higher solubility, piperine molecules move closer and farther apart several times during the simulation, which indicates the formation of a less stable dimer in water. In contrast, both curcumin and piperine are soluble in ethanol and, thus, dimers can hardly be formed in this media. In comparison with a pure-water solvent, a 30 : 70 mixture of ethanol and water significantly reduces the probability of formation of most dimers of curcumin and piperine molecules. The simulations show that larger clusters may be complex structures, but the formation of stacks (in the case of piperine and enol tautomer of curcumin) and cages (when the keto tautomer of curcumin is involved) are not rare. Furthermore, it is shown that each single molecule presents a certain degree of mobility in the cluster, especially on the surface, but without leading to dissociation.

Primary resistance to integrase strand transfer inhibitors in Spain using ultrasensitive HIV-1 genotyping.

BACKGROUND: Transmission of resistance mutations to integrase strand transfer inhibitors (INSTIs) in HIV-infected patients may compromise the efficacy of first-line antiretroviral regimens currently recommended worldwide. Continued surveillance of transmitted drug resistance (TDR) is thus warranted. OBJECTIVES: We evaluated the rates and effects on virological outcomes of TDR in a 96 week prospective multicentre cohort study of ART-naive HIV-1-infected subjects initiating INSTI-based ART in Spain between April 2015 and December 2016. METHODS: Pre-ART plasma samples were genotyped for integrase, protease and reverse transcriptase resistance using Sanger population sequencing or MiSeq™ using a ≥ 20% mutant sensitivity cut-off. Those present at 1%-19% of the virus population were considered to be low-frequency variants. RESULTS: From a total of 214 available samples, 173 (80.8%), 210 (98.1%) and 214 (100.0%) were successfully amplified for integrase, reverse transcriptase and protease genes, respectively. Using a Sanger-like cut-off, the overall prevalence of any TDR, INSTI-, NRTI-, NNRTI- and protease inhibitor (PI)-associated mutations was 13.1%, 1.7%, 3.8%, 7.1% and 0.9%, respectively. Only three (1.7%) subjects had INSTI TDR (R263K, E138K and G163R), while minority variants with integrase TDR were detected in 9.6% of subjects. There were no virological failures during 96 weeks of follow-up in subjects harbouring TDR as majority variants. CONCLUSIONS: Transmitted INSTI resistance remains rare in Spain and, to date, is not associated with virological failure to first-line INSTI-based regimens.

Diffusive process under Lifshitz scaling and pandemic scenarios.

We here propose to model active and cumulative cases data from COVID-19 by a continuous effective model based on a modified diffusion equation under Lifshitz scaling with a dynamic diffusion coefficient. The proposed model is rich enough to capture different aspects of a complex virus diffusion as humanity has been recently facing. The model being continuous it is bound to be solved analytically and/or numerically. So, we investigate two possible models where the diffusion coefficient associated with possible types of contamination are captured by some specific profiles. The active cases curves here derived were able to successfully describe the pandemic behavior of Germany and Spain. Moreover, we also predict some scenarios for the evolution of COVID-19 in Brazil. Furthermore, we depicted the cumulative cases curves of COVID-19, reproducing the spreading of the pandemic between the cities of São Paulo and São José dos Campos, Brazil. The scenarios also unveil how the lockdown measures can flatten the contamination curves. We can find the best profile of the diffusion coefficient that better fit the real data of pandemic.

Sun Protection Habits and Sunburn in Elite Aquatics Athletes: Surfers, Windsurfers and Olympic Sailors.

The objective of this study was to analyse the sun exposure habits of elite aquatics athletes, together with their sunburn history and skin examination habits, taking into account differences by sex and between sports. A cross-sectional health survey was conducted at world championship events during which elite surfers, windsurfers and Olympic sailors from 30 different countries were invited to participate. The athletes were asked to complete a self-administered questionnaire focused on sun protection habits, sun exposure and sports practices. The survey was completed by 240 athletes, 171 men (71.3%) and 69 women (28.8%), with a mean age of 22 years (SD 5.86) and skin phototypes I (6.3%), II (3.3%), III (22.0%), IV (32.5%), V (9.2%) and VI (1.7%). There were significant differences between male and female athletes in skin self-examination (p < 0.001) and in the use of sunglasses (p < 0.001). In sunburn history during the last season, there were significant differences (p < 0.001) among the three sports analysed, in both sexes. The mean rate of sunburn during the previous season was 76.7%, and 27.5% of participants reported having experienced three or more sunburns that lasted at least 1 day. This type of athlete is at high risk of sunburn and hence of future skin cancer. However, there is a general lack of awareness of this risk. This study highlights the need to inform such athletes and to raise awareness of the dangers, through educational interventions on the importance of protecting against sunburn in order to reduce the future incidence of skin cancer.

Long-term effectiveness of recommended boosted protease inhibitor-based antiretroviral therapy in Europe.

OBJECTIVES: The aim of the study was to evaluate the long-term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)-, darunavir/ritonavir (DRV/r)-, and lopinavir/ritonavir (LPV/r)-containing regimens. METHODS: Data were analysed for 5678 EuroSIDA-enrolled patients starting a DRV/r-, ATZ/r- or LPV/r-containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART-naïve subjects (8%) at ritonavir-boosted protease inhibitor (PI/r) initiation; (2) ART-experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV-1 RNA copies/mL; and (3) ART-experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL. Virological failure (VF) was defined as two consecutive VL measurements >200 copies/mL ≥24 weeks after PI/r initiation. Kaplan-Meier and multivariable Cox models were used to compare risks of failure by PI/r-based regimen. The main analysis was performed with intention-to-treat (ITT) ignoring treatment switches. RESULTS: The time to VF favoured DRV/r over ATZ/r, and both were superior to LPV/r (log-rank test; P < 0.02) in all analyses. Nevertheless, the risk of VF in ART-naïve patients was similar regardless of the PI/r initiated after controlling for potential confounders. The risk of VF in both treatment-experienced groups was lower for DRV/r than for ATZ/r, which, in turn, was lower than for LPV/r-based ART. CONCLUSIONS: Although confounding by indication and calendar year cannot be completely ruled out, in ART-experienced subjects the long-term effectiveness of DRV/r-containing regimens appears to be greater than that of ATZ/r and LPV/r.

Muscle strength is associated with lower diastolic blood pressure in schoolchildren.

Cardiorespiratory fitness (CRF) provides protection against the elevated blood pressure in overweight youth. Less is known regarding any similar protective effect of muscular fitness. We investigated how handgrip strength, an easy to implement measure of muscular strength, interacted with CRF and BMI to determine blood pressure in youth. We measured systolic (SBP) and diastolic (DBP) blood pressure, handgrip strength (HG), CRF and body mass index (BMI) in n=7329 10-16year-olds (47% girls). We defined elevated blood pressure as >91st percentile and Good HG as >33rd percentile. Participants were classified as Fit or Unfit and as Normal or Overweight/Obese based on international standards. The prevalence of elevated SBP was 23%, and 44% of participants had elevated DBP. In unfit participants Good HG was associated with lower SBP (z=0.41 (95%CI: 0.20-0.61) and DBP (z=0.29 (95%CI: 0.12-0.47). In Overweight/Obese participants, DBP was z=0.24 (95%CI: 0.14-0.34) lower in the Good (versus Low) HG group. Overweight/Obese participants with Good HG also had a 32% lower risk of elevated DBP (OR: 0.68, 95%CI: 0.57-0.82). This association was attenuated but remained important after adjusting for BMI (20% risk reduction, OR: 0.80, 95%CI: 0.63-1.01). Muscular fitness appears to play some protective role against the risk of elevated blood pressure; particularly for the more prevalent measure: elevated DBP (44%). Effects may be restricted to Overweight / Obese or unfit youth, who have an increased risk of elevated BP and also may be less likely to engage in traditional cardiorespiratory fitness training. Research to determine the effects of muscular fitness training on blood pressure is warranted in these subgroups.

Curcumin enhances the activity of fluconazole against Cryptococcus gattii-induced cryptococcosis infection in mice.

AIM: The aim of this study was to investigate the in vitro and in vivo activities of pure curcumin, as well as its combination with fluconazole, against Cryptococcus gattii. METHODS AND RESULTS: The minimal inhibitory concentrations (MIC) of curcumin and its interactions with fluconazole against C. gattii were assessed in vitro using standard methods. This same combination was used to treat C. gattii-induced cryptococcosis in mice. The behavioural and functional assessment of the mice during treatment was also performed. The average MIC for curcumin was 19·8 µg ml(-1) . Its combination with fluconazole resulted in FICΣ (fractional inhibitory concentration index) values between 0·79 and 2·29. Curcumin (alone or combined with fluconazole) significantly reduced pulmonary damage and fungal burden in the brain. No colonies were found in the brain following combination treatment, which was also confirmed by the improved behaviour of mice. CONCLUSIONS: The combination therapy with curcumin and fluconazole was the most effective among the treatments tested, as in addition to reducing the fungal burden and damage on lung tissues, it was able to eliminate the fungal burden in the brain, enhancing the survival of mice. SIGNIFICANCE AND IMPACT OF THE STUDY: This study points to the possibility of using curcumin in combination with fluconazole as a clinical treatment of cryptococcosis.

Physical fitness as a mediator between objectively measured physical activity and clustered metabolic syndrome in children and adolescents: The UP&DOWN study.

BACKGROUND AND AIMS: The extent to which physical fitness (PF) attenuates or modifies the association between physical activity (PA) and clustered metabolic syndrome risk factors (CMetSRF) is controversial. We aimed: i) To examine the independent and combined association of objectively measured PA and PF with CMetSRF in children and adolescents; ii) To test the mediating effect of PF in the association of PA with CMetSRF. METHODS AND RESULTS: A total of 226 children and 256 adolescents participated. Levels of PA (light, moderate, vigorous and moderate-to-vigorous [MVPA]) and PF were measured by accelerometry and ALPHA battery, respectively. Cardiorespiratory and muscular fitness values were combined in a global PF variable. A CMetSRF was computed by assessing the following variables: waist circumference, systolic blood pressure, high-density lipoprotein cholesterol, triglycerides and glucose. In children, the highest vigorous PA (ß = -0.193; P = 0.003) and MVPA (ß = -0.149; P = 0.025) were individually associated with lower CMetSRF, but these associations were not independent of global PF. In adolescents, the association of moderate (ß = -0.123; P = 0.046) and MVPA (ß = -0.147; P = 0.024) with CMetSRF was independent of PF. Among unfit adolescents, the higher time they spent in MVPA the lower CMetSRF levels were found (P = 0.032). CONCLUSIONS: The results are suggestive of a full mediation of global PF in the association of MVPA and vigorous PA with CMetSRF in children. In adolescents, the association of higher moderate and MVPA with lower CMetSRF was independent of levels of PF, and mediation analyses suggest only a partial mediation of global PF in the association of MVPA with CMetSRF.

Primary resistance to integrase strand-transfer inhibitors in Europe.

OBJECTIVES: The objective of this study was to define the natural genotypic variation of the HIV-1 integrase gene across Europe for epidemiological surveillance of integrase strand-transfer inhibitor (InSTI) resistance. METHODS: This was a multicentre, cross-sectional study within the European SPREAD HIV resistance surveillance programme. A representative set of 300 samples was selected from 1950 naive HIV-positive subjects newly diagnosed in 2006-07. The prevalence of InSTI resistance was evaluated using quality-controlled baseline population sequencing of integrase. Signature raltegravir, elvitegravir and dolutegravir resistance mutations were defined according to the IAS-USA 2014 list. In addition, all integrase substitutions relative to HXB2 were identified, including those with a Stanford HIVdb score ≥ 10 to at least one InSTI. To rule out circulation of minority InSTI-resistant HIV, 65 samples were selected for 454 integrase sequencing. RESULTS: For the population sequencing analysis, 278 samples were retrieved and successfully analysed. No signature resistance mutations to any of the InSTIs were detected. Eleven (4%) subjects had mutations at resistance-associated positions with an HIVdb score ≥ 10. Of the 56 samples successfully analysed with 454 sequencing, no InSTI signature mutations were detected, whereas integrase substitutions with an HIVdb score ≥ 10 were found in 8 (14.3%) individuals. CONCLUSIONS: No signature InSTI-resistant variants were circulating in Europe before the introduction of InSTIs. However, polymorphisms contributing to InSTI resistance were not rare. As InSTI use becomes more widespread, continuous surveillance of primary InSTI resistance is warranted. These data will be key to modelling the kinetics of InSTI resistance transmission in Europe in the coming years.

[Economic evaluation studies in diagnostic imaging: justification and critical reading]. / Estudios de evaluación económica en diagnóstico por imagen. Justificación y lectura crítica.

First, this article describes the concepts and tools most widely used for economic evaluation in healthcare. Second, it discusses some elements that must be taken into account in the social decision about how much we are willing to spend to prolong a person's life by one year. Third, it describes the criteria recommended for the critical analysis of publications that evaluate the economic aspects of health interventions. Finally, several studies about ultrasound screening for aneurysms of the abdominal aorta are used as illustrative examples to show how these elements and criteria can be applied.

Animal Approaches to Studying Risk Factors for Parkinson's Disease: A Narrative Review.

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.

Virtual bronchoscopy for evaluating cervical tumors of the fetus.

We report on four cases of fetal cervical tumor, comprising three lymphangiomas and one teratoma, evaluated by ultrasound and magnetic resonance imaging (MRI) between 26 and 37 weeks' gestation. The aim was to investigate the use of virtual bronchoscopy to evaluate fetal airway patency in each case. A three-dimensional (3D) model of the airway was created from overlapping image layers generated by MRI. The files obtained were manipulated using 3D modeling software, allowing the virtual positioning of observation cameras, adjustment of lighting parameters and creation of simulated 3D movies for analysis of a virtual path through the model. In all fetuses, fetal airway patency was clearly demonstrated by virtual bronchoscopy and this was confirmed postnatally. MRI with virtual bronchoscopy could become a useful tool for studying fetal airway patency in cases of cervical tumor.

Antibacterial activity of Thymus vulgaris (thyme) essential oil against strains of Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus saprophyticus isolated from meat product.

Meat products represent an important component of the human diet and are a good source of nutrients. Food-borne microorganisms are the main pathogens that cause human diseases as a result of food consumption, especially products of animal origin. The objective of the present research was to verify the antibacterial activity of the essential oil of Thymus vulgaris against strains of Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus saprophyticus isolated from meat products. For this, the analyses of Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were performed in microdilution plates. The association of the product with antimicrobials was also studied using disk diffusion. And the anti-adherent activity, which was determined in the presence of sucrose, in glass tubes. Thyme oil showed a strong inhibitory activity against K. pneumoniae, P. aeruginosa and S. saprophyticus, with the MIC values ranging from 64 to 512 µg/mL, and bactericidal effect for most strains, with MBC values ranging from 256 to 1,024 µg/mL. T. vulgaris oil exhibited varied interactions in association with the antimicrobials, with synergistic (41.67%), indifferent (50%) and antagonistic (8.33%) effects. Regarding the anti-adherent activity, the test product was effective in inhibiting the adherence of all bacterial strains under study. Therefore, thyme oil presents itself as an antibacterial and anti-adherent agent against K. pneumoniae, P. aeruginosa and S. saprophyticus, being a natural product that can represent an interesting alternative in the efforts to combat foodborne diseases.

Simple method for culture of peripheral blood lymphocytes of Testudinidae.

We developed and optimized a simple, efficient and inexpensive method for in vitro culture of peripheral blood lymphocytes from the Brazilian tortoise Chelonoidis carbonaria (Testudinidae), testing various parameters, including culture medium, mitogen concentration, mitotic index, culture volume, incubation time, and mitotic arrest. Peripheral blood samples were obtained from the costal vein of four couples. The conditions that gave a good mitotic index were lymphocytes cultured at 37°C in minimum essential medium (7.5 mL), with phytohemagglutinin as a mitogen (0.375 mL), plus streptomycin/penicillin (0.1 mL), and an incubation period of 72 h. Mitotic arrest was induced by 2-h exposure to colchicine (0.1 mL), 70 h after establishing the culture. After mitotic arrest, the cells were hypotonized with 0.075 M KCl for 2 h and fixed with methanol/acetic acid (3:1). The non-banded mitotic chromosomes were visualized by Giemsa staining. The diploid chromosome number of C. carbonaria was found to be 52 in females and males, and sex chromosomes were not observed. We were able to culture peripheral blood lymphocytes of a Brazilian tortoise in vitro, for the preparation of mitotic chromosomes.

Additive manufacturing models of fetuses built from three-dimensional ultrasound, magnetic resonance imaging and computed tomography scan data.

OBJECTIVE: To generate physical fetal models using images obtained by three-dimensional ultrasonography (3DUS), magnetic resonance imaging (MRI) and computed tomography (CT) to guide additive manufacturing technology. METHODS: Images from 33 fetuses, including three sets of twins, were used. Fifteen fetuses were normal and evaluated only by 3DUS. Eighteen cases had abnormalities such as conjoined twins, tumors, aneuploidy, skeletal abnormalities, central nervous system abnormalities and facial or thoracic defects. Scans were performed using high-resolution 3DUS. In cases of abnormalities, MRI and CT were performed on the same day as 3DUS. The images obtained with 3DUS, CT or MRI were exported to a workstation in DICOM format. A single observer performed slice-by-slice manual segmentation using a digital high-definition screen. Software that converts medical images into numerical models was used to construct virtual 3D models, which were physically realized using additive manufacturing technologies. RESULTS: Physical models based on 3DUS, MRI and CT images either separately or combined were successfully generated. They were remarkably similar to the postnatal appearance of the aborted fetus or newborn baby, especially in cases with pathology. CONCLUSION: The use of 3DUS, MRI and CT may improve our understanding of fetal anatomical characteristics, and these technologies can be used for educational purposes and as a method for parents to visualize their unborn baby. The images can be segmented and applied separately or combined to construct 3D virtual and physical models.

Antiviral activity of Bignoniaceae species occurring in the State of Minas Gerais (Brazil): part 1.

AIMS: To evaluate the antiviral activity of Bignoniaceae species occurring in the state of Minas Gerais, Brazil. METHODS AND RESULTS: Ethanol extracts of different anatomical parts of bignoniaceous plant species have been evaluated in vitro against human herpesvirus type 1 (HSV-1), vaccinia virus (VACV) and murine encephalomyocarditis virus (EMCV) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A total of 34 extracts from 18 plant species selected according to ethnopharmacological and taxonomic criteria were screened. Fifteen of the 34 extracts (44.1%) have disclosed antiviral activity against one or more of the viruses assayed with EC(50) values in the range of 23.2 ± 2.5-422.7 ± 10.9 µg ml(-1). CONCLUSIONS: Twelve of the 34 extracts (35.3%) might be considered promising sources of antiviral natural products, as they have shown EC50 ≤ 100 µg ml(-1). The present screening discloses the high potential of the Bignoniaceae family as source of antiviral agents. SIGNIFICANCE AND IMPACT OF THE STUDY: Active extracts were identified and deserve bioguided studies for the isolation of antiviral compounds and studies on mechanism of action.

DNA extraction from hair shafts of wild Brazilian felids and canids.

Wild felids and canids are usually the main predators in the food chains where they dwell and are almost invisible to behavior and ecology researchers. Due to their grooming behavior, they tend to swallow shed hair, which shows up in the feces. DNA found in hair shafts can be used in molecular studies that can unravel, for instance, genetic variability, reproductive mode and family structure, and in some species, it is even possible to estimate migration and dispersion rates in given populations. First, however, DNA must be extracted from hair. We extracted successfully and dependably hair shaft DNA from eight wild Brazilian felids, ocelot, margay, oncilla, Geoffroy's cat, pampas cat, jaguarundi, puma, and jaguar, as well as the domestic cat and from three wild Brazilian canids, maned wolf, crab-eating fox, and hoary fox, as well as the domestic dog. Hair samples came mostly from feces collected at the São Paulo Zoo and were also gathered from non-sedated pet or from recently dead wild animals and were also collected from museum specimens. Fractions of hair samples were stained before DNA extraction, while most samples were not. Our extraction protocol is based on a feather DNA extraction technique, based in the phenol:chloroform:isoamyl alcohol general method, with proteinase K as digestive enzyme.