The Braincase and Neurosensory Anatomy of an Early Jurassic Marine Crocodylomorph: Implications for Crocodylian Sinus Evolution and Sensory Transitions

This is the pre-peer reviewed version of the following article: Brusatte, S. L., Muir, A. , Young, M. T., Walsh, S. , Steel, L. and Witmer, L. M. (2016), The Braincase and Neurosensory Anatomy of an Early Jurassic Marine Crocodylomorph: Implications for Crocodylian Sinus Evolution and Sensory Transitions. Anat. Rec., 299: 1511-1530., which has been published in final form at doi:10.1002/ar.23462. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving." You are advised to consult the published version if you wish to cite from it

Potential use of rhizobium for vegetable crops growth promotion

The system of vegetable crops production required large amounts of mineral fertilizers. One of the possible alternatives to assure the economic and environmental sustainability of this production system would be the use of promoting growth plant rhizobacteria (PGPR). However, care is needed to select a microorganism to be used in crops that are usually consumed raw, so human health is not at risk. It was important to search for PGPR, as rhizobium, that already were broadly used as inoculants for leguminous plants for several decades, without risks to human health. PGPR can promote growth and development of plants through direct and indirect mechanisms, by production and secretion of chemical substances in the rhizosphere. The direct mechanisms were involved with the uptake of nutrients by the plants (nitrogen, phosphorus and essential minerals) through phosphate solubilization, production of siderophores and growth regulators. The indirect mechanisms were involved with the decrease of inhibitory effects from various pathogenic agents related with biological pest control, thereby favoring plant growth. Nevertheless, due to its ability to promote beneficial effects to plants, effective bacterial colonization was extremely important. Some bacteria that colonized the rhizoplane may penetrate the plant roots and some strains may move to the aerial part, with decreased bacterial density, compared with colonizing populations in the rhizosphere or roots. It can be concluded that Rhizobia promotes plant growth using different mechanisms as biological nitrogen fixation and production of different plant growth regulators (e.g. auxins). Therefore, new studies with Rhizobia characterization and observation about its different mechanisms of promoting plant growth should be performed. Such information would be useful for the identification of plants with potential to increase agricultural production due to the benefits of using plant growth promoter’s rhizobia

Inoculação e coinoculação de rizobactérias promotoras de crescimento em plantas de arroz irrigado

Aiming at obtaining high productivity and reduction of production costs, new techniques have been studied in rice crops, such as the use of plant growth promoting rhizobacteria (PGPR). The objective of this study was to evaluate the efficiency of inoculation and co-inoculation of rhizobia and Azospirillum brasilense in promoting the growth of irrigated rice plants cultivated in the field. Two experiments were conducted in the field, in the 2014/15 and 2015/16 crops, at the Rio Grande do Sul Rice Experiment Station. The experiment was composed of seven treatments, with two control treatments, without inoculation (81 kg ha-1 N and 135 kg ha-1 N, equivalent to 60% and 100%, respectively, of the recommended nitrogen dose). The other five treatments received only 60% of the N dose and were inoculated with the UFRGS Vp16 (Burkholderia sp.) and UFRGS Lc348 (Mesorhizobium sp.) Rhizobia, and with the commercial product containing the A. brasilense AbV5 and AbV6 strains. Inoculation and co-inoculation with PGPR may represent a viable alternative to reduce the amount of nitrogen fertilizers in rice crops.Visando a obtenção de altas produtividades e redução dos custos de produção, novas técnicas vêm sendo estudadas nas lavouras de arroz, como a utilização de rizobactérias promotoras de crescimento de plantas (RPCPs). O objetivo do trabalho foi avaliar a eficiência da inoculação e coinoculação de rizóbios e Azospirillum brasilense na promoção de crescimento de plantas de arroz irrigado cultivadas a campo. Foram conduzidos dois experimentos a campo, nas safras 2014/15 e 2015/16, na Estação Experimental do Instituto Rio Grandense do Arroz. O experimento foi composto por sete tratamentos, sendo dois tratamentos controle, sem inoculação (81 kg ha-1 de N e 135 kg ha-1 N, equivalente a 60% e 100%, respectivamente, da dose de nitrogênio recomendada). Os outros cinco tratamentos receberam apenas 60% da dose de N e foram inoculados com os rizóbios UFRGS Vp16 (Burkholderia sp.) e UFRGS Lc348 (Mesorhizobium sp.), e com o produto comercial contendo as estirpes de A. brasilense AbV5 e AbV6. A inoculação e coinoculação com RPCPs podem representar uma alternativa viável para reduzir a quantidade de adubos nitrogenados nas lavouras de arroz

First-line treatment of malignant glioma with carmustine implants followed by concomitant radiochemotherapy: a multicenter experience

Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. But these studies and subsequent non-phase III studies have also shown risks associated with local chemotherapy within the central nervous system. The introduction of concomitant radiochemotherapy with temozolomide (TMZ) has later demonstrated a survival benefit in a phase III trial and has become the current treatment standard for newly diagnosed malignant glioma patients. Lately, this has resulted in clinical protocols combining local chemotherapy with BCNU wafers and concomitant radiochemotherapy with TMZ although this may carry the risk of increased toxicity. We have compiled the treatment experience of seven neurosurgical centers using implantation of carmustine wafers at primary surgery followed by 6 weeks of radiation therapy (59–60 Gy) and 75 mg/m2/day TMZ in patients with newly diagnosed glioblastoma followed by TMZ monochemotherapy. We have retrospectively analyzed the postoperative clinical course, occurrence and severity of adverse events, progression-free interval, and overall survival in 44 patients with newly diagnosed glioblastoma multiforme. All patients received multimodal treatment including tumor resection, BCNU wafer implantation, and concomitant radiochemotherapy. Of 44 patients (mean age 59 ± 10.8 years) with glioblastoma who received Gliadel wafer at primary surgery, 28 patients (64%) had died, 16 patients (36%) were alive, and 15 patients showed no evidence of clinical or radiographic progression after a median follow-up of 15.6 months. At time of analysis of adverse events in this patient population, the median overall survival was 12.7 months and median progression-free survival was 7.0 months. Surgical, neurological, and medical adverse events were analyzed. Twenty-three patients (52%) experienced adverse events of any kind including complications that did not require treatment. Nineteen patients (43%) experienced grade 3 or grade 4 adverse events. Surgical complications included cerebral edema, healing abnormalities, cerebral spinal fluid leakage, meningitis, intracranial abscess, and hydrocephalus. Neurological adverse events included newly diagnosed seizures, alteration of mental status, and new neurological deficits. Medical complications were thromboembolic events (thrombosis, pulmonary embolism) and hematotoxicity. Combination of both treatment strategies, local chemotherapy with BCNU wafer and concomitant radiochemotherapy, appears attractive in aggressive multimodal treatment schedules and may utilize the sensitizing effect of TMZ and carmustine on MGMT and AGT on their respective drug resistance genes. Our data demonstrate that combination of local chemotherapy and concomitant radiochemotherapy carries a significant risk of toxicity that currently appears underestimated. Adverse events observed in this study appear similar to complication rates published in the phase III trials for BCNU wafer implantation followed by radiation therapy alone, but further add the toxicity of concomitant radiochemotherapy with systemic TMZ. Save use of a combined approach will require specific prevention strategies for multimodal treatments

Retargeted adenoviruses for radiation-guided gene delivery

The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78 kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment

Development of a web-based insulin decision aid for the elderly: usability barriers and guidelines

In recent years, researchers have attempted to shift patient decision aids (PDAs) from paper-based to web-based to increase its accessibility. Insulin decision aids help diabetes patients, most of whom are elderly to make an informed decision to start insulin. However, the lack of usability guidelines applicable for such target group causes developers to struggle to answer the challenging question ‘How can such web service be made usable, and, ultimately, acceptable and accessible for elderly patients?’. Hence, the purpose of this study is to identify the common usability requirements that may facilitate good practices to empower elderly diabetes patients in utilizing a web-based insulin decision aid for their benefit. We set out an approach to use prototyping and retrospective think-aloud techniques to explore web usability barriers that elderly patients may encounter when using an insulin decision aid web site and use the feedback for improving the prototype. Usability requirements were captured iteratively through scoping, brainstorming, prototype, testing and evaluating. The study suggests that the insights from experts and users are equally important to assure the validity of the identified usability guidelines; they reflect the accessibility needs of the aging community while complementing the key requirements of an insulin decision aid. The study contributes to recommend web usability guidelines backed by a series of expert and user evaluations which could be a proactive resource to improve usability, acceptability and accessibility of online insulin decision aids for elderly with diabetes

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate <0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P < 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

Positive predictive value of automated database records for diabetic ketoacidosis (DKA) in children and youth exposed to antipsychotic drugs or control medications: a tennessee medicaid study

<p>Abstract</p> <p>Background</p> <p>Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of treatment with some atypical antipsychotic drugs in children and <b>youth</b>. Because drug-associated DKA is rare, large automated health outcomes databases may be a valuable data source for conducting pharmacoepidemiologic studies of DKA associated with exposure to individual antipsychotic drugs. However, no validated computer case definition of DKA exists. We sought to assess the positive predictive value (PPV) of a computer case definition to detect incident cases of DKA, using automated records of Tennessee Medicaid as the data source and medical record confirmation as a "gold standard."</p> <p>Methods</p> <p>The computer case definition of DKA was developed from a retrospective cohort study of antipsychotic-related type 2 diabetes mellitus (1996-2007) in Tennessee Medicaid enrollees, aged 6-24 years. Thirty potential cases with any DKA diagnosis (ICD-9 250.1, ICD-10 E1x.1) were identified from inpatient encounter claims. Medical records were reviewed to determine if they met the clinical definition of DKA.</p> <p>Results</p> <p>Of 30 potential cases, 27 (90%) were successfully abstracted and adjudicated. Of these, 24 cases were confirmed by medical record review (PPV 88.9%, 95% CI 71.9 to 96.1%). Three non-confirmed cases presented acutely with severe hyperglycemia, but had no evidence of acidosis.</p> <p>Conclusions</p> <p>Diabetic ketoacidosis in children and youth can be identified in a computerized Medicaid database using our case definition, which could be useful for automated database studies in which drug-associated DKA is the outcome of interest.</p