Application of ribotyping and IS<i>200</i> fingerprinting to distinguish the five <i>Salmonella</i> serotype O6,7:c:1,5 groups: Choleraesuis <i>sensu stricto</i>, Choleraesuis var. Kunzendorf, Choleraesuis var. Decatur, Paratyphi C, and Typhisuis

Sixty-seven strains of the five described Salmonella serotypes having antigens 6,7:c: 1,5, that is S. enterica serotype Choleraesuis sensu stricto, Choleraesuis var. Kunzendorf, Choleraesuis var. Decatur, Paratyphi C, and Typhisuis, were examined for 16S rrn profile ribotype, presence of IS200 and phenotypic characters, including rate of change of flagellar-antigen phase and nutritional character. Choleraesuis sensu stricto and its Kunzendorf variant had related but distinct ribotypes. Therefore, ribotyping appears to be a suitable method for differentiating Choleraesuis non-Kunzendorf from Choleraesuis var. Kunzendorf. Some strains of Paratyphi C had 16S profiles that resembled that of Choleraesuis non-Kunzendorf, while others resembled that of Choleraesuis var. Kunzendorf. The Typhisuis profiles were like those of Choleraesuis non-Kunzendorf, while the Choleraesuis var. Decatur profiles were unlike those of any of the other four groups. Furthermore, IS200 fingerprinting discriminated between Choleraesuis var. Decatur and the other strains with antigenic formula O6,7:c: 1,5, and comparison of IS200 patterns showed a high degree of genetic divergence within Choleraesuis var. Decatur. Our findings show that ribotyping and IS200 fingerprinting, combined with classical microbiological methods, distinguish the groups Choleraesuis non-Kunzendorf, Choleraesuis var. Kunzendorf, Choleraesuis var. Decatur, Paratyphi C and Typhisuis

On polynomial Trefftz spaces for the linear time-dependent Schr\"odinger equation

We study the approximation properties of complex-valued polynomial Trefftz spaces for the $(d+1)$-dimensional linear time-dependent Schr\"odinger equation. More precisely, we prove that for the space-time Trefftz discontinuous Galerkin variational formulation proposed by G\'omez, Moiola (SIAM. J. Num. Anal. 60(2): 688-714, 2022), the same $h$-convergence rates as for polynomials of degree $p$ in $(d + 1)$ variables can be obtained in a mesh-dependent norm by using a space of Trefftz polynomials of anisotropic degree. For such a space, the dimension is equal to that of the space of polynomials of degree $2p$ in $d$ variables, and bases are easily constructed

Airway obstruction produces widespread sympathoexcitation: role of hypoxia, carotid chemoreceptors, and NTS neurotransmission

Obstructive sleep apnea (OSA) is the most common respiratory disturbance of sleep and is closely associated to cardiovascular diseases. In humans, apnea increases respiratory effort and elevates muscle sympathetic nerve activity (SNA), but the primary stimulus for the SNA activation has not been identified. We recently developed a model of apnea in rodents using acute airway obstruction. In this study, we employed this model to test whether the elevation in SNA was mediated by hypoxia, carotid chemoreceptors, or neurotransmission in the nucleus tractus solitarius (NTS). In anesthetized, male Sprague-Dawley rats, airway obstruction (20s) increased phrenic nerve activity (PNA), arterial blood pressure (ABP), and lumbar, renal, and splanchnic SNA. The changes in SNA were similar across all three sympathetic nerves. Inactivation of chemoreceptors by hyperoxia (100% O-2) or surgical denervation of carotid chemoreceptors attenuated, but did not eliminate, the changes in SNA and ABP produced by airway obstruction. To interrupt afferent information from carotid chemoreceptor and extracarotid afferents to the hindbrain, airway obstruction was performed before and after NTS microinjection of the GABA(A) agonist muscimol or a cocktail of NMDA and non-NMDA antagonists. Inhibition of NTS neurons or blockade of glutamatergic receptors attenuated the increase in lumbar SNA, splanchnic SNA, renal SNA, and PNA. Collectively, these findings suggest that PNA and SNA responses induced by airway obstruction depend, in part, on chemoreceptors afferents and glutamatergic neurotransmission in the NTS.National Heart, Lung, and Blood Institute GrantAmerican Heart Association Established Investigator AwardCoordination of Training of Higher Education Graduate Foundation (CAPES)National Council for Scientific and Technological Development (CNPq)Univ Fed Sao Paulo, Dept Physiol, Sao Paulo, SP, BrazilUniv Pittsburgh, Sch Med, Dept Med, Div Renal Electrolyte, Pittsburgh, PA 15213 USAUniv Pittsburgh, Sch Med, Hypertens Ctr, Pittsburgh, PA USAUniv Fed Sao Paulo, Dept Physiol, Sao Paulo, SP, BrazilNational Heart, Lung, and Blood Institute Grant: R01 HL113270Web of Scienc

Randomised trial of oral versus sequential intravenous/oral cephalosporins in children with pyelonephritis

The hypothesis was tested that oral antibiotic treatment in children with acute pyelonephritis and scintigraphy-documented lesions is equally as efficacious as sequential intravenous/oral therapy with respect to the incidence of renal scarring. A randomised multi-centre trial was conducted in 365 children aged 6 months to 16years with bacterial growth in cultures from urine collected by catheter. The children were assigned to receive either oral ceftibuten (9mg/kg once daily) for 14days or intravenous ceftriaxone (50mg/kg once daily) for 3days followed by oral ceftibuten for 11days. Only patients with lesions detected on acute-phase dimercaptosuccinic acid (DMSA) scintigraphy underwent follow-up scintigraphy. Efficacy was evaluated by the rate of renal scarring after 6 months on follow-up scintigraphy. Of 219 children with lesions on acute-phase scintigraphy, 152 completed the study; 80 (72 females, median age 2.2 years) were given ceftibuten and 72 (62 females, median age 1.6years) were given ceftriaxone/ceftibuten. Patients in the intravenous/oral group had significantly higher C-reactive protein (CRP) concentrations at baseline and larger lesion(s) on acute-phase scintigraphy. Follow-up scintigraphy showed renal scarring in 21/80 children treated with ceftibuten and 33/72 with ceftriaxone/ceftibuten (p = 0.01). However, after adjustment for the confounding variables (CRP and size of acute-phase lesion), no significant difference was observed for renal scarring between the two groups (p = 0.2). Renal scarring correlated with the extent of the acute-phase lesion (r = 0.60, p < 0.0001) and the grade of vesico-ureteric reflux (r = 0.31, p = 0.03), and was more frequent in refluxing renal units (p = 0.04). The majority of patients, i.e. 44 in the oral group and 47 in the intravenous/oral group, were managed as out-patients. Side effects were not observed. From this study, we can conclude that once-daily oral ceftibuten for 14days yielded comparable results to sequential ceftriaxone/ceftibuten treatment in children aged 6months to 16years with DMSA-documented acute pyelonephritis and it allowed out-patient management in the majority of these childre

Desenvolvimento e Investimento de Startups brasileiras: a percepção de múltiplos stakeholders / Development and Investment of Brazilian Startups: the perception of multiple stakeholders

Empresas que tendem a criar negócios disruptivos influenciados pelas oportunidades geradas pelos avanços tecnológicos, estão envolvidas em um ambiente de desafios e incertezas. Frente a isso, este trabalho tem por objetivo analisar a percepção dos stakeholders de startups diante das incertezas e desafios nas diferentes fases de investimento no Brasil. Para tal, esta pesquisa de cunho qualitativo, utilizou três diferentes tipos de roteiros estruturados, que possibilitaram a execução de entrevistas com 9 indivíduos, divididos em três classes: empreendedor, especialista e investidor. Com base nas discussões abordadas sobre o estudo, é possível encontrar potenciais contribuições desta pesquisa. Primeiramente, uma visão dos principais stakeholders envolvidos no desenvolvimento de startups em diferentes momentos de investimento, seja em estágios iniciais do desenvolvimento do produto/serviço ou até mesmo em fase de maturação. A contribuição da pesquisa consiste na ampliação e descrição do fenômeno de como startups sobrevivem diante de um ambiente com alto grau de incerteza e competem por diferentes fontes de investimento. 

Transporters in Drug Development: 2018 ITC Recommendations for Transporters of Emerging Clinical Importance

This white paper provides updated International Transporter Consortium (ITC) recommendations on transporters that are important in drug development following the 3rd ITC workshop. New additions include prospective evaluation of organic cation transporter 1 (OCT1) and retrospective evaluation of organic anion transporting polypeptide (OATP)2B1 because of their important roles in drug absorption, disposition, and effects. For the first time, the ITC underscores the importance of transporters involved in drug-induced vitamin deficiency (THTR2) and those involved in the disposition of biomarkers of organ function (OAT2 and bile acid transporters)

Virulence Attenuation and Live Vaccine Potential of aroA, crp cdt cya, and Plasmid-Cured Mutants of Salmonella enterica Serovar Abortusovis in Mice and Sheep

Three live vaccine candidates of Salmonella enterica subspecies I serotype Abortusovis (aroA, cya crp cdt, and plasmid-cured strains) have been developed, and their efficacies in inducing humoral antibodies and protecting against abortion after challenge with wild-type strain SS44 were evaluated in sheep. Following estrus synchronization, animals were immunized 3 weeks after fertilization and boosted once 3 weeks later. Following challenge with wild-type SS44, pregnancy failure of vaccinated ewes was reduced compared to that of nonimmunized controls. Attenuation of each vaccine was also assessed in challenge experiments with nonimmunized pregnant ewes and in BALB/c mice. All three vaccine candidates appear to be safe for use in sheep and provide a model for the development of live vaccine candidates against naturally occurring ovine salmonellosis