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.

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.

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.

Evaluación de los efectos de un dispositivo de entrenamiento de los músculos inspiratorios sobre la oxigenación muscular y la activación neuromuscular de los músculos respiratorios / [Evaluation of the effects of an inspiratory muscle training device on muscle oxygenation and neuromuscular activation of the respiratory muscles]

Objetivo: Comparar los cambios en la actividad electromiográfica y oxigenación muscular periférica de los músculos intercostales, en su condición de musculatura accesoria a la respiración, en pacientes con EPOC durante la realización de un test de marcha de 6 minutos (TM6M) con y sin el uso de un dispositivo FeelBreathe (FB).Material y métodos: Se seleccionaron a 20 sujetos diagnosticados de EPOC a los que se les realizaron dos TM6M separados al menos por 60 minutos. Aleatoriamente, cada uno de los pacientes realizó dos TM6M, uno usando el dispositivo FB y el otro sin FB (SFB) y se midieron durante la realización de ambos TM6M la actividad electromiográfica (EMG) obteniéndose la raíz de la media cuadrática (RMS), y por otro lado la oxigenación tisular de los músculos intercostales a través de la variable de oxihemoglobina (HbO2).Resultados: No hubo diferencias significativas en la distancia recorrida en ambos TM6M con FC a SFB. Tanto la RMS como la oxigenación tisular mostraron valores similares entre la condición FB vs. SFB al final de ambas pruebas (32,26 ± 101,94 μV vs 28,25 ± 87,02 μV; p = 0,16 y 70,63 ± 18,80 vs 70,74 ± 16,77; p = 0,975 respectivamente).Conclusiones: El estímulo de trabajo de la musculatura intercostal durante el TM6M con el dispositivo FB no compromete la aparición de la fatiga temprana por un exceso de activación o disminución de la oxigenación de dichos músculos al nivel de intensidad del TM6M. (AU)

Objective: To compare changes in electromyographic activity and peripheral muscle oxygenation of the intercostal muscles, in their condition as accessory muscles for respiration, in patients with COPD during a 6-minute walk test (6MWT) with and without the use of a FeelBreathe (FB) device.Material and methods: 20 subjects diagnosed with COPD who underwent two 6MTMs separated by at least 60 minutes were selected. Randomly, each of the patients underwent two 6MWT, one using the FB device and the other without FB (SFB) and electromyographic activity (EMG) was measured during the performance of both 6MWT, obtaining the root mean square (RMS), and on the other hand, tissue oxygenation of the intercostal muscles through the oxyhemoglobin (HbO2) variable.Results: There were no significant differences in the distance traveled in both 6MWT with HR to SFB. Both RMS and tissue oxygenation showed similar values between the FB condition vs. SFB at the end of both tests (32.26 ± 101.94 μV vs 28.25 ± 87.02 μV; p = 0.16 and 70.63 ± 18.80 vs 70.74 ± 16.77; p = 0.975 respectively).Conclusions: The work stimulus of the intercostal muscles during the 6MWT with the FB device does not compromise the appearance of early fatigue due to excessive activation or decreased oxygenation of these muscles at the intensity level of the 6MWT. (AU)

SNPs from BCHE and DRD3 genes associated to cocaine abuse amongst violent individuals from Sao Paulo, Brazil.

Violence and drug abuse are highly destructive phenomena found world-wide, especially in Brazil. They seem to rise proportionally to one another and possibly related. Additionally, genetics may also play a role in drug abuse. This study has focused on identifying the use of cocaine within postmortem cases arriving at the Institute of Legal Medicine of Sao Paulo as well as the presence of certain single nucleotide polymorphisms (SNPs) to better understand one's susceptibility to abuse the drug. Both hair and blood samples have been extracted through a simple methanol overnight incubation or a rapid dilute-and-shoot method, respectively. The samples were then analyzed using an UPLC-ESI-MS/MS and genotyped through RT-PCR. Statistical analyses were performed via SPSS software. From 105 postmortem cases, 53% and 51% of the cases shown to be positive for cocaine in hair and blood, respectively. Genetic wise, a significant difference has been observed for SNP rs4263329 from the BCHE gene with higher frequencies of the genotypes A/G and G/G seen in cocaine users (OR=8.91; 95%CI=1.58-50.21; p=0.01). Likewise, also SNP rs6280 from the DRD3 gene presented a significant association, with both genotypes T/C and C/C being more frequent in users (OR=4.96; 95% CI=1.07-23.02; p=0.04). To conclude, a rather high proportion of cocaine has been found, which may suggest a connotation between the use of the drug and risky/violent behaviors. Additionally, significant associations were also found within two SNPs related to cocaine use, however, due to several inherent limitations, these must be confirmed.

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.

Anticryptococcal activity of hexane extract from Spondias tuberosa Arruda and associated cellular events.

Cryptococcosis is an opportunistic systemic mycosis whose treatment is limited to three drugs. In this work, we evaluated the antifungal activity of a hexane extract (HE) from Spondias tuberosa leaves against Cryptococcus neoformans and Cryptococcus gattii. Minimal inhibitory concentrations (MIC) were determined, and putative mechanisms were evaluated by flow cytometry. In addition, an in vivo infection assay was performed using Tenebrio molitor larvae. Treatment with HE inhibited the growth of standard and clinical isolates of C. neoformans and C. gattii (MICs ranging from 0.78 to 3.12mg/mL), significantly (P<0.05) increased mitochondrial superoxide anion levels, and induced mitochondrial membrane depolarization, loss of lysosomal membrane integrity, and phosphatidylserine externalization. The mean survival time of C. gattii-infected T. molitor larvae significantly (P<0.05) increased from 1.225 days in control to 3.067 and 3.882 days in HE-treated groups (78 and 156mg/kg, respectively). In conclusion, HE showed anticryptococcal activity, induced mitochondrial and lysosomal damage in yeast cells, and exhibited anti-infective action against C. gattii in T. molitor larvae.

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.

Cognitive and anxiety-like impairments accompanied by serotonergic ultrastructural and immunohistochemical alterations in early stages of parkinsonism.

Parkinson's disease (PD) is mostly known as a dopamine deficiency syndrome due the structural and functional changes in striatal projection neurons. However, studies have considered this pathology as a multi-systemic disease in which the neurodegenerative process extends beyond the dopaminergic system. Therefore, the purpose of the present study was to investigate the morphological and immunohistochemical changes associated with behavioral and cognitive alterations in a model of parkinsonism induced by low dose of reserpine. Animals showed anxiety-like behavior and deficits in short-term recognition memory. Besides, Tyrosine Hydroxylase (TH) immunoreactive cells decreased in reserpine (RES) group in CA1 and serotonin (5-HT) immunoreactive cells decreased in RES group in CA1, CA3 and medial prefrontal cortex (mPFC). Moreover, an increase in the area (µm2) of 5 H T labeled ultrastructure (axon terminal) was observed in RES group only in CA1 and mPFC. The evidence of alterations in 5-HT immunoreactive in the premotor phase of model of parkinsonism highlights the importance of looking beyond the nigrostriatal system to elucidate the underling mechanisms and deficits in other neurotransmitters systems. This provides vital information regarding novel interventions for the management of non-motor symptoms. Additionally, the low-dose reserpine treatment has an early effect on axonal ultrastructure. As the axonopathy in PD has been increasingly recognized, the focus on axonal neurobiology is noteworthy for both neuroprotective and restorative therapeutics, and the progressive reserpine rat model can be a useful tool in this search.

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.

Morfologia e dinâmica testicular em cutias (Dasyprocta prymnolopha) adultas / Testicular morphology and dynamic in adult agoutis (Dasyprocta prymnolopha)

Este trabalho objetivou apresentar a caracterização da morfologia do testículo de cutia (Dasyproctaprymnolopha) macho, com o intuito de colaborar com o conhecimento da morfofisiologia reprodutiva da espécie. Foram utilizados testículos de 47 animais, com idade entre um e dois anos, pesos homogêneos (2,08 ± 0,23kg), oriundos do Núcleo de Estudos e Preservação de Animais Silvestres do Centro de Ciências Agrárias da Universidade Federal do Piauí. As estruturas foram dissecadas, descritas, e fragmentos foram processados para a microscopia de luz, sendo, posteriormente avaliada a atividade gonadal. Observou-se que os testículos são órgãos elipsoides alongados, podendo ser encontrados na região inguinal ou na cavidade abdominal, não apresentando um escroto bem delimitado. Verificou-se também parênquima com característica histológica padrão para o órgão em mamíferos, com a identificação de oito tipos de associações celulares, caracterizando os estádios do ciclo do epitélio seminífero, com menor e maior frequência dos estádios 3 e 5, respectivamente.(AU)

This study meant to characterize the morphology of the testicle from (Dasyprocta prymnolopha) agouti males, in order to collaborate with the knowledge of reproductive morphophysiology of the specie. Testicles were used from 47 animals aged between 1 and 2 years, homogeneous weight (2.08±0.23kg), coming from the Centre for the Study and Conservation of Wild Animals of Agricultural Sciences Center of the Federal University of Piauí. The structures were dissected, described and fragments were processed for light microscopy, and, subsequently, gonadal activity was evaluated. Testes were observed to be elongated ellipsoidal bodies that can be found in the groin or in the abdominal cavity, not having a clearly defined scrotum. We also could see parenchymal with standard histological characteristic for the mammalian body, with the identification of eight types of cell associations, characterized epithelium Seminiferous stages of the cycle, with lower and higher frequency of stages 3 and 5, respectively.(AU)

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.

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.

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.

A new method for recognizing hand configurations of Brazilian gesture language.

This paper describes a new method for recognizing hand configurations of the Brazilian Gesture Language - LIBRAS - using depth maps obtained with a Kinect® camera. The proposed method comprised three phases: hand segmentation, feature extraction, and classification. The segmentation phase is independent from the background and depends only on pixel depth information. Using geometric operations and numerical normalization, the feature extraction process was done independent from rotation and translation. The features are extracted employing two techniques: (2D)2LDA and (2D)2PCA. The classification is made with a novelty classifier. A robust database was constructed for classifier evaluation, with 12,200 images of LIBRAS and 200 gestures of each hand configuration. The best accuracy obtained was 95.41%, which was greater than previous values obtained in the literature.