Spontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson's Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and alpha-Synuclein Expression

Reserpine is an irreversible inhibitor of vesicular monoamine transporter-2 (VMAT2) used to study Parkinson's disease (PD) and screening for antiparkinsonian treatments in rodents. Recently, the repeated treatment with a low-dose of reserpine was proposed as a progressive model of PD. Rats under this treatment show progressive catalepsy behavior, oral movements and spontaneous motor activity decrement. In parallel, compared to Wistar rats, spontaneously hypertensive rats (SHR) are resistant to acute reserpine-induced oral dyskinesia. We aimed to assess whether SHR would present differential susceptibility to repeated reserpine-induced deficits in the progressive model of PD. Male Wistar and SHR rats were administered 15 subcutaneously (s.c.) injections of reserpine (0.1 mgkg) or vehicle, every other day and motor activity was assessed by the catalepsy, oral movements and open field tests. Only reserpine-treated Wistar rats presented increased latency to step down in the catalepsy test and impaired spontaneous activity in the open field. On the other hand, there was an increase in oral movements in both reserpine-treated strains, although with reduced magnitude and latency to instauration in SHR. After a 15-day withdrawn period, both strains recovered from motor impairment, but SHR animals expressed reduced latencies to reach control levels. Finally, we performed immunohistochemistry for tyrosine hydroxylase (TH) and a-synuclein (alpha-syn) 48 h after the last injection or 15 days after withdrawn. Reserpinetreated animals presented a reduction in TH and an increase in alpha-syn immunoreactivity in the substantia nigra and dorsal striatum (dSTR), which were both recovered after 15 days of withdraw. Furthermore, SHR rats were resistant to reserpine-induced TH decrement in the substantia nigra, and presented reduced immunoreactivity to a-syn inthe dSTR relative to Wistar rats, irrespective of treatment. This effect was accompanied by increase of malondaldhyde (MDA) in the striatum of reserpine-treated Wistar rats, while SHR presented reduced MDA in both control and reserpine conditions relative to Wistar strain. In conclusion, the current results show that SHR are resilient to motor and neurochemical impairments induced by the repeated low-dose reserpine protocol. These findings indicate that the neurochemical, molecular and genetic differences in the SHR strain are potential relevant targets to the study of susceptibility to PD.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Fundacao de Apoio a Pesquisa do Estado do Rio Grande do Norte (FAPERN)Pro-reitoria de Pesquisa da Universidade Federal do Rio Grande do Norte (PROPESQ/UFRN)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Univ Fed Rio Grande do Norte, Dept Physiol, Memory Studies Lab, Natal, RN, BrazilUniv Fed Rio Grande do Norte, Brain Inst, Natal, RN, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Behav Neurosci Lab, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, BrazilUniv Fed Rio Grande do Norte, Dept Physiol, Neurochem Studies Lab, Natal, RN, BrazilUniv Santa Catarina, Dept Cellular Biol Embryol & Genet, Lab Behav Genet, Florianopolis, SC, BrazilUniv Fed Sao Paulo, Dept Biosci, Santos, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Behav Neurosci Lab, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Biosci, Santos, BrazilFAPESP: 2015/12308-5FAPESP: 2015/03354-3Web of Scienc

IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population

Background: IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not. Aims: To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry. Methods: rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers. Results: IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 x 10(-5)). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/ relapse (NR/R) (P = 8.00 x 10(-3)). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 x 10(-3)), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 x 10(-3) and P = 2.16 x 10(-2) respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 x 10(-3)); Amerindian and European ancestry genetic contribution were greater in the SVR group. Conclusion: IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.Fapesb [SUS0001/2011]Fapesp [10/10.549-1

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Enhanced remote areas communications: the missing scenario for 5G and beyond 5G networks

The next generation of mobile communication system will allow a plethora of new services and use cases. By offering support for high throughput connections, low latency response and massive number of connections, the fifth generation of the mobile network will trigger applications unseen in any other network. However, one important application scenario is not being properly addressed by the players responsible for the mobile networks' standardization, that is the remote and rural areas network. This scenario requires large cells with high throughput, flexibility to opportunistically exploit free bands below 1 GHz and spectrum agility to change the operational frequency when an incumbent is detected. Incipient actions are being considered for the Release 17 but based on the new radio specification as starting point. The limitations imposed by orthogonal waveforms in the physical layers hinder the exploitation of vacant TV channels in rural and remote areas. 5G-RANGE, a Brazil-Europe bilateral cooperation project, aims at conceiving, implementing and deploying an innovative mobile network, designed to provide reliable and cost-effective connection in these regions. This network can be seamlessly integrated with the other 5G scenarios, closing the connectivity gap between the urban, rural and remote areas. Hence, 5G-RANGE network is an interesting complementary solution for beyond 5G standards. This paper presents the major achievements of the 5G-RANGE project, from the design of the physical, medium access control and network layers, to the field demonstrations. The paper also covers the business models that can be used to make the deployment of this technology a reality.This work was supported in part by the European Union's Horizon 2020 Research and Innovation Programme under Grant 777137 (5G-RANGE Project), in part by the Centro de Pesquisa e Desenvolvimento em Tecnologias Digitais para Informação e Comunicação /Rede Nacional de Pesquisa (CTIC/RNP)/Ministério da Ciência, Tecnologia, Informação e Comunicação (MCTIC) through the 4a. Chamada Coordenada Brazil Europe (BR-EU) em Tecnologias da Informação e Comunicação (TICS), and in part by the Conselho Nacional de Desenvolvimento Cientí co e Tecnológico (CNPq)-Brazil under Grant 05085/2018-2. Computations were performed in part at the Center for Information Services and High Performance Computing at Technische Universität Dresden

Analysis of the bearing capacity of continuous flight auger piles in terms of their excavation energy and of rainfall data

Continuous flight auger piles (CFAs) are among the most common types of foundation executed in the tropical residual soil of Brasília, DF, Brazil. The bearing capacity of CFAs can be controlled according to the energy required to excavate each pile but is also influenced by seasonal conditions that affect the unsaturated soil profile. In the present article, a database of controlled execution of CFAs carried out at Brasília-DF was evaluated. The execution methodology enabled the full control of the drilling energy. Load tests were also performed and the pile bearing capacity was estimated by extrapolating the load-settlement curve using the van Der Veen method. As the site was excavated before the foundation was built, the morphology of the site was also considered in the analyses. Furthermore, by comparing the execution energies and climatological information, a relation between the moisture indexes and the execution energies was investigated. From these analyses, discussions regarding the relation between the bearing capacity of the piles tested and the rainfall regime they have been subjected to are presented. The changes observed in bearing capacity due to climatological effects may lead to economical savings and offer enhanced reliability in the design of CFAs

5-HT(1B) receptor in the suprachiasmatic nucleus of the common marmoset (Callithrix jacchus)

Serotonin (5-HT) is involved in the fine adjustments at several brain centers including the core of the mammal circadian timing system (CTS) and the hypothalamic suprachiasmatic nucleus (SCN). The SCN receives massive serotonergic projections from the midbrain raphe nuclei, whose inputs are described in rats as ramifying at its ventral portion overlapping the retinohypothalamic and geniculohypothalamic fibers. In the SCN, the 5-HT actions are reported as being primarily mediated by the 5-HT1 type receptor with noted emphasis for 5-HT(1B) subtype, supposedly modulating the retinal input in a presynaptic way. In this study in a New World primate species, the common marmoset (Callithrix jacchus), we showed the 5-HT(1B) receptor distribution at the dorsal SCN concurrent with a distinctive location of 5-HT-immunoreactive fibers. This finding addresses to a new discussion on the regulation and synchronization of the circadian rhythms in recent primates. (C) 2010 Elsevier Ireland Ltd. All rights reserved.CNPqConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CAPESCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)PROPESQ-UFRNPROPESQ-UFRNFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPES

Risk assessment of trihalomethanes from tap water in Fortaleza, Brazil

The cancer risks (CR) by oral ingestion, dermal absorption, and inhalation exposure of trihalomethanes (THM) from tap water of ten districts in Fortaleza, Brazil were estimated. The mean levels of THM compounds were obtained in Fortaleza tap water as follow: 63.9 mu g L(-1) for chloroform (CHCl(3)), 40.0 mu g L(-1) for bromodichloromethane (CHBrCl(2)), and 15.6 mu g L(-1) for dibromochloromethane (CHBr(2)Cl). Bromoform (CHBr(3)) was not detected. The mean CR for THMs in tap water is 3.96 x 10(-4). The results indicate that Fortaleza residents have a higher CR by inhalation than dermal absorption and oral ingestion. The CR for CHCl(3) contributes with 68% as compared with the total CR, followed by CHBrCl(2) (21%), and CHBr(2)Cl (11%). The hazard index (HI) is about ten times lower than unity, not indicating non-cancer effects.National Council for Scientific and Technological Development (CNPq, Brazil)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Technological Development Park (PADETEC)Technological Development Park (PADETEC

Exposure to an enriched environment facilitates motor recovery and prevents short-term memory impairment and reduction of striatal BDNF in a progressive pharmacological model of parkinsonism in mice

Previous studies showed that the repeated administration with a low dose of reserpine (RES) induces a gradual appearance of motor signs and cognitive deficits compatible with parkinsonism in rodents. Environmental stimulation has neuroprotective effects in animal models of neurodegenerative damage, including acutely induced parkinsonism. We investigated the effects of exposure to an enriched environment (EE) on motor, cognitive and neuronal (levels of tyrosine hydroxylase, TH and brain derived neurotrophic factor, BDNF) deficits induced by a progressive model of Parkinson's disease (PD) in mice. Male mice were repeatedly treated with vehicle or 0.1 mg/kg of RES (s.c) and kept under two housing conditions: standard environment (SE) and EE. In animals kept in SE, the treatment with RES induced deficits in motor function (catalepsy test, open field and oral movements), in novel object recognition (NOR) and plus-maze discriminative avoidance tasks. The environmental stimulation facilitated the recovery of motor deficits assessed by the catalepsy test after the end of treatment. Additionally, exposure to EE prevented the memory deficit in the NOR task. Treatment with RES induced a reduction in the number of TH positive cells in SNpc and VTA, which recovered 30 days after the end of treatment. Finally, RES reduced the levels of BDNF in the striatum and the exposure to the EE prevented this effect. These results suggest that plastic brain changes induced by EE promote beneficial effects on the progression of neuronal impairment related to PD.Coordenacao de Aperfeigoamento de Pessoal de Nivel Superior (CAPES)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Univ Fed Rio Grande do Norte, Dept Physiol, Memory Studies Lab, Natal, RN, BrazilUniv Fed Sergipe, Dept Biosci, Lab Behav & Evolutionary Neurosci, Itabaiana, SE, BrazilUniv Fed Rio Grande do Norte, Dept Physiol, Lab Neurochem Studies, Natal, RN, BrazilUniv Fed Sao Paulo, Dept Biosci, Lab Neurosci & Bioprospecting Nat Prod, Santos, SP, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Behav Neurosci Lab, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biosci, Lab Neurosci & Bioprospecting Nat Prod, Santos, SP, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Behav Neurosci Lab, Sao Paulo, SP, BrazilCAPESCNPQFAPESP: 2015/03354-3Web of Scienc

Data from: Zoonotic infection of Brazilian primate workers with New World simian foamy virus

Simian foamy viruses (SFVs) are retroviruses present in nearly all nonhuman primates (NHPs), including Old World primates (OWP) and New World primates (NWP). While all confirmed human infections with SFV are from zoonotic transmissions originating from OWP, little is known about the zoonotic transmission potential of NWP SFV. We conducted a longitudinal, prospective study of 56 workers occupationally exposed to NWP in Brazil. Plasma from these workers was tested using Western blot (WB) assays containing NWP SFV antigens. Genomic DNA from blood and buccal swabs was analyzed for the presence of proviral SFV sequences by three nested PCR tests and a new quantitative PCR assay. Exposure histories were obtained and analyzed for associations with possible SFV infection. Ten persons (18%) tested seropositive and two persons were seroindeterminate (3.6%) for NWP SFV. Six persons had seroreactivity over 2-3 years suggestive of persistent infection. All SFV NWP WB-positive workers reported at least one incident involving NWP, including six reporting NWP bites. NWP SFV viral DNA was not detected in the blood or buccal swabs from all 12 NWP SFV seroreactive workers. We also found evidence of SFV seroreversion in three workers suggestive of possible clearance of infection. Our findings suggest that NWP SFV can be transmitted to occupationally-exposed humans and can elicit specific humoral immune responses but infection remains well-controlled resulting in latent infection and may occasionally clear