hybridModels: An R Package for the Stochastic Simulation of Disease Spreading in Dynamic Networks

Disease spreading simulations are traditionally performed using coupled differential equations. However, in the setting of metapopulations, most of the solutions provided by this method do not account for the dynamic topography of subpopulations. Conversely, the alternative approach of individual-based modeling (IBM) may add computational cost and complexity. Hybrid models allow for the study of disease spreading because they combine both aforementioned approaches by separating them across different scales: a local scale that addresses subpopulation dynamics using coupled differential equations and a global scale that addresses the contact between these subpopulations using IBM. We present a simple way of simulating the spread of disease in dynamic networks using the high-level statistical computational language R and the hybridModels package. We built four examples using disease spread models at the local scale in several different networks: an animal movement network; a three-node network, whose model solution using a stochastic simulation algorithm is compared with the ordinary differential equations approach; the commuting of individuals between patches, which we compare with the permanent migration of individuals; and the commuting of individuals within the metropolitan area of São Paulo

Avian infectious bronchitis vírus (IBV): effect of vaccine doses on mucosal imune responses and protection after challenge in chickens.

Projeto/Plano de Ação: 05.11.11.002

Immune-protection mechanisms against late challenge with avian infectious bronchitis vírus (IBV) induced by a single-dose of an attenuated vaccine in day-old chicks.

Projeto/Plano de Ação: 05.11.11.00

High Salinity Tolerance of Aedes to Breed in Brackish Waters Around the Negombo Estuary

In the midst of dengue control programs, a high occurrence of dengue and dengue hemorrhagic fever cases around the Negombo estuary is reported at the Centre for Clinical Management of Dengue & Dengue Haemorrhagic Fever, Negombo, during April/May and Sept/Oct 2014. Although preimaginal development of Aedes-dengue vector mosquito is known to exist in fresh water environment for many years, few recent findings have revealed the possibility of Aedes breeding and immature stage development in brackish water conditions. In Negombo estuary-being a partially enclosed coastal body of brackish water, we investigated the possible Aedes mosquito breeding in brackish water in and around the lagoon. Natural breeding sources were examined, and an ovitrap based study was also carried out to investigate the possible breeding, immature stage development, hatching and adult emergence in brackish water environment. The study revealed the oviposition preference (0-22 ppt), egg hatching (0-6 ppt in field conditions and 0-6 ppt in laboratory conditions for Ae.aegypti; 0-14 ppt in field conditions and 0-18 ppt in laboratory conditions for Ae. albopictus) and preimaginal development (0-6 ppt in field conditions and 0-6 ppt in laboratory conditions for Ae.aegypti; 0-14 ppt in field conditions and 0-14 ppt in laboratory conditions for Ae.albopictus) of Aedes mosquitoes. Further, the study reported the natural prevalence of preimaginal stages of Ae.albopictus in brackish water collections (2-14 ppt) around the estuary. The study confirmed the brackish water breeding of Aedes mosquitoes around the Negombo estuary. Higher salinity tolerance, compared to brackish water collections of the Northern coast, Sri Lanka was revealed. Negombo, being a fishing village and having a high population density, the study identifies the potential risk of dengue transmission in the area by providing breeding grounds for vector mosquitoes and possibly explains the high occurrence of dengue incidence around the lagoon. Further, the study suggests incorporating larvivorus fish and removing trapped receptacles in the marshy environments to intensify the control programs.Keywords: Salinity tolerance, Aedes, Negombo lagoo

Bacterial cellulose as a support for the growth of retinal pigment epithelium

The feasibility of bacterial cellulose (BC) as a novel substrate for retinal pigment epithelium (RPE) culture was evaluated. Thin (41.6 ± 2.2 m of average thickness) and heatdried BC substrates were surface modified via acetylation and polysaccharide adsorption, using chitosan and carboxymethyl cellulose. All substrates were characterized according to their surface chemistry, wettability, energy, topography and also regarding their permeability, dimensional stability, mechanical properties and endotoxin content. Then, their ability to promote RPE cell adhesion and proliferation in vitro was assessed. All surface-modified BC substrates presented similar permeation coefficients with solutes of up to 300 kDa. Acetylation of BC decreased its swelling and the amount of endotoxins. Surface modification of BC greatly enhanced the adhesion and proliferation of RPE cells. All samples showed similar stress-strain behavior; BC and acetylated BC showed the highest elastic modulus, but the latter exhibited a slightly smaller tensile strength and elongation at break as compared to pristine BC. Although similar proliferation rates were observed among the modified substrates, the acetylated ones showed higher initial cell adhesion. This difference may be mainly due to the moderately hydrophilic surface obtained after acetylation.The authors acknowledge the Portuguese Foundation for Science and Technology (FCT, Portugal) for the financial support provided by the Research Grants SERH/BD/63578/2009, SFRH/BD/64901/2009, SFRH/BPD/64958/2009, and SFRH/BPD/63148/2009 for S.G., J.P., J.P.S., and V.S., respectively. The authors also acknowledge the Projects PEst-OE/EQB/LA0004/2013, PEst-OE/EQB/LA0023/2013, PTDC/BBB-BQB/2450/2012, and RECI/BBB-EBI/0179/2012 (Number: FCOMP-01-0124-FEDER-027462), cofunded by QREN, FEDER

Sympathetic hyperactivity, increased tyrosine hydroxylase and exaggerated corpus cavernosum relaxations associated with oxidative stress plays a major role in the penis dysfunction in townes sickle cell mouse

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOSickle cell disease patients display priapism that may progress to erectile dysfunction. However, little is known about the pathophysiological alterations of corpus cavernosum in sickle cell disease. Objective Thus, this study aimed to evaluate the functional and molecular alterations of sympathetic machinery and nitric oxide-cyclic guanosine monophosphate signaling pathway in Townes transgenic sickle cell disease mice. Methods Concentration-response curves to contractile (phenylephrine) and relaxant agents (acetylcholine and sodium nitroprusside) were obtained in corpus cavernosum strips from sickle and C57BL/6 (control) mice. Neurogenic contractions and nitrergic relaxations were obtained using electrical-field stimulation. Measurements of endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), phosphodiesterase-5 (PDE5) and a alpha(1A)-, alpha(1B)-and alpha(1D)-adrenoceptor mRNA expressions and reactive-oxygen species were performed. Tyrosine hydroxylase phosphorylated at Ser-31 and total tyrosine hydroxylase protein expressions in cavernosal tissues were also measured. Results The neurogenic contractions were higher in the sickle cell disease group, in association with elevated tyrosine hydroxylase phosphorylated at Ser-31 and total tyrosine hydroxylase protein expression, as well as increased tyrosine hydroxylase mRNA expression. Likewise, phenylephrine-induced contractions were greater in the sickle mice, whereas a alpha(1A)-, alpha(1B)-and alpha(1D)-adrenoceptor mRNA expression remained unchanged. Cavernosal relaxations to acetylcholine, sodium nitroprusside and EFS were higher in sickle mice, accompanied by decreased eNOS and nNOS, along with lower PDE5 mRNA expression. An increase of about 40% in reactive-oxygen species generation in corpus cavernosum from sickle mice was also detected. Conclusion Our study shows that decreased nitric oxide bioavailability in erectile tissue due to increased oxidative stress leads to both sympathetic hyperactivity and dysregulation of nitric oxide signaling in corpus cavernosum from Townes sickle mice.Sickle cell disease patients display priapism that may progress to erectile dysfunction. However, little is known about the pathophysiological alterations of corpus cavernosum in sickle cell disease. Objective Thus, this study aimed to evaluate the functional and molecular alterations of sympathetic machinery and nitric oxide-cyclic guanosine monophosphate signaling pathway in Townes transgenic sickle cell disease mice. Methods Concentration-response curves to contractile (phenylephrine) and relaxant agents (acetylcholine and sodium nitroprusside) were obtained in corpus cavernosum strips from sickle and C57BL/6 (control) mice. Neurogenic contractions and nitrergic relaxations were obtained using electrical-field stimulation. Measurements of endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), phosphodiesterase-5 (PDE5) and a alpha(1A)-, alpha(1B)-and alpha(1D)-adrenoceptor mRNA expressions and reactive-oxygen species were performed. Tyrosine hydroxylase phosphorylated at Ser-31 and total tyrosine hydroxylase protein expressions in cavernosal tissues were also measured. Results The neurogenic contractions were higher in the sickle cell disease group, in association with elevated tyrosine hydroxylase phosphorylated at Ser-31 and total tyrosine hydroxylase protein expression, as well as increased tyrosine hydroxylase mRNA expression. Likewise, phenylephrine-induced contractions were greater in the sickle mice, whereas a alpha(1A)-, alpha(1B)-and alpha(1D)-adrenoceptor mRNA expression remained unchanged. Cavernosal relaxations to acetylcholine, sodium nitroprusside and EFS were higher in sickle mice, accompanied by decreased eNOS and nNOS, along with lower PDE5 mRNA expression. An increase of about 40% in reactive-oxygen species generation in corpus cavernosum from sickle mice was also detected. Conclusion Our study shows that decreased nitric oxide bioavailability in erectile tissue due to increased oxidative stress leads to both sympathetic hyperactivity and dysregulation of nitric oxide signaling in corpus cavernosum from Townes sickle mice.1112FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2013/19781-2; 2014/00984-