Costellotherkildsen3361

On the basis of previous reports showing alum neurotoxic effects in CD1 mice, an additional experiment was done, and showed early brain translocation at day 45 of alum injected subcutaneously at 200 μg Al/kg. This study confirms the striking biopersistence of alum. It points out an unexpectedly delayed diffusion of the adjuvant in lymph nodes and spleen of CD1 mice, and suggests the importance of mouse strain, route of administration, and doses, for future studies focusing on the potential toxic effects of aluminum-based adjuvants.

To determine whether small head circumference (HC) or birth weight (BW) or both are associated with neonatal and long-term neurologic outcome in very preterm infants.

All 2442 live births from the 1997 Epipage study between 26 and 32 weeks of gestational age in 9 regions of France were analyzed. A total of 1395 were tested at age 5 years for cognitive performance and 1315 with school performance reports at age 8 years. Symmetric growth restriction (SGR) was defined by HC and BW <20th percentile and in the same percentile range, and asymmetric growth restriction by at least 1 of HC and BW <20th percentile and the other in a higher decile range. There were 2 forms of asymmetric growth restriction head growth restriction (HGR) and weight growth restriction (WGR). Appropriate for gestational age was defined by both BW and HC >20th percentile.

Compared with appropriate for gestational age, SGR was significantly associated with neonatal mortality (aOR 2.99, 95% CI 1.78-5.03), moderate and severe cognitive deficiency (aOR 1.65, 95% CI 1.01-2.71 and aOR 2.61, 95% CI 1.46-4.68, respectively), and poor school performance (aOR 1.79; 95% CI 1.13-2.83). HGR was significantly associated with severe cognitive deficiency (aOR 2.07, 95% CI 1.15-3.74). WGR was not significantly associated with cognitive or school performance despite higher rates of neonatal morbidity.

SGR in preterm infants was associated with neonatal mortality and impaired cognitive and school performance. The outcome of asymmetric growth restriction differed according to HC. HGR was associated with impaired cognitive function; WGR was not.

SGR in preterm infants was associated with neonatal mortality and impaired cognitive and school performance. The outcome of asymmetric growth restriction differed according to HC. HGR was associated with impaired cognitive function; WGR was not.

To compare global and regional cerebral perfusion in newborns with congenital heart disease (CHD) and healthy controls using arterial spin labeling (ASL) magnetic resonance imaging (MRI) prior to open heart surgery.

We performed brain MRIs in 101 newborns (58 controls, 43 CHD) using 3-dimensional fast spin echo pseudo-continuous ASL. Cerebral blood flow (CBF) ASL images were linearly coregistered to T2-weighted images for anatomic delineation and selection of regions-of-interest. Anatomic regions included frontal white matter (FWM), occipital white matter (OWM), thalami, and basal ganglia (BG).

Newborns with single ventricle CHD demonstrated significantly lower global (P = .044) and regional BG (P = .025) CBF compared with controls. Mean regional CBF in the thalami in cyanotic newborns with CHD was lower compared with controls (P = .004). Mean regional CBF in thalami (P = .02), BG (P = .01), and OWM (P = .03) among newborns with cyanotic CHD was lower than those with acyanotic CHD. Newborns with CHD ventilated prior to MRI had increased global (P = .016) and OWM (P = .013) CBF compared with those not ventilated.

Newborns with uncorrected cyanotic or single ventricle CHD show disturbances in cerebral perfusion compared to healthy controls using ASL. Cardiac physiology and preoperative hemodynamic compromise play an important role in preoperative alterations in global and regional cerebral perfusion. Our data suggest that ASL may be useful for studying cerebral perfusion in newborns at high risk for cerebral ischemia, such as those with complex CHD.

Newborns with uncorrected cyanotic or single ventricle CHD show disturbances in cerebral perfusion compared to healthy controls using ASL. Cardiac physiology and preoperative hemodynamic compromise play an important role in preoperative alterations in global and regional cerebral perfusion. Our data suggest that ASL may be useful for studying cerebral perfusion in newborns at high risk for cerebral ischemia, such as those with complex CHD.

Several different acquired resistance mechanisms to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy have been described. Although rare, the transformation from adenocarcinoma to small cell carcinoma (SCLC) is one of these important mechanisms. We report a rare case that indicates transformation into large-cell neuroendocrine carcinoma (LCNEC) as an acquired resistance mechanism to EGFR-TKI therapy.

The patient was a 68-year-old male with a diagnosis of cT2N2M0 pulmonary adenocarcinoma with L858R mutation on exon 21. He received lobectomy and underwent several courses of chemotherapies, including EGFR-TKIs, each time he relapsed. He finally relapsed with a mass that protruded into his left main bronchus. Resection of the metastatic site identified LCNEC that retained the original EGFR mutation. Immunohistochemistry revealed the loss of expression of EGFR and retinoblastoma (Rb) in the LCNEC.

This case highlights acquisition of EGFR-TKI resistance by transformation to LCNEC, not SCLC. Loss of EGFR and Rb expression in the LCNEC suggests the same mechanism as transformation to SCLC. Further study is needed to elucidate this mechanism, especially regarding the similarities and differences to SCLC.

This case highlights acquisition of EGFR-TKI resistance by transformation to LCNEC, not SCLC. Loss of EGFR and Rb expression in the LCNEC suggests the same mechanism as transformation to SCLC. Further study is needed to elucidate this mechanism, especially regarding the similarities and differences to SCLC.

Although lung cancer is of high epidemiological relevance in Germany, evidence on its economic implications is scarce. Sound understanding of current care structures and associated expenditures is required to comprehensively judge the additional benefit of novel interventions in lung cancer care. Adopting a payer perspective, our study aims to analyze expenditures for individuals with incident lung cancer.

Patients with an initial diagnosis of lung cancer (ICD-10 code C34) in 2009 were searched in a large, nationwide base of health insurance claims data and grouped according to initial treatment (Surgery, Chemotherapy/Radiotherapy, No specific treatment). All-cause SHI and lung cancer-related spending was assessed for a patient-individual three-year time frame after initial diagnosis. read more Expenditures per case and expenditures per year survived were calculated via Generalized Linear Gamma Models adjusted for age, gender, living region, baseline metastases, multiple tumors and initial treatment regimen using tveness analyses of screening and prevention schemes, or prognostic models of life-time expenditures per lung cancer case.

Analyses of lung cancer-related expenditures need to take into account treatment strategies and survival. Our study is representative for a large share of the population and provides detailed, patient-level information on costs of care and their compilation. Results render estimates available for the cost of lung cancer e.g. for budget impact analyses, cost-effectiveness analyses of screening and prevention schemes, or prognostic models of life-time expenditures per lung cancer case.Plant parasitic nematodes are devastating pests on many crops. Juveniles (J2) of cyst nematodes invade the roots to induce a syncytium. This feeding site is their only source of nutrients. Male nematodes leave the roots after the fourth molt to mate with females. The females stay attached to their syncytia throughout their life and produce hundreds of eggs, which are contained in their bodies. When the females die their bodies form the cysts, which protect the eggs. Cysts can survive for many years in the soil until favorable conditions induce hatching of the juveniles. The beet cyst nematode Heterodera schachtii (H. schachtii)is a pathogen of sugar beet (Beta vulgaris) but can also complete its life cycle on Arabidopsis roots growing on agar plates under sterile conditions. We present here protocols for a stock culture of H. schachtii and an infection assay on agar plates.This protocol describes an effective method of in situ RT-PCR that was developed to localize specific gene expression directly in thin cross-sections of nematode feeding sites induced by the cyst nematode Heterodera schachtii (H. schachtii) or the root-knot nematode Meloidogyne incognita (M. incognita) in Arabidopsis roots using DIG (Digoxigenin-11dUTP) labeling coupled with AP (alkaline phosphatase) and nitro-blue tetrazolium/5-bromo-4-chloro-3'-indolylphosphate-based detection. This method is applicable to any other Arabidopsis root tissue.Rhamnogalacturonan I (RGI) is a pectic polysaccharide composed of a backbone of alternating rhamnose and galacturonic acid residues with side chains containing galactose and/or arabinose residues. The structure of these side chains and the degree of substitution of rhamnose residues are extremely variable and depend on species, organs, cell types and developmental stages. Deciphering RGI function requires extending the current set of monoclonal antibodies (mAbs) directed to this polymer. Here, we describe the generation of a new mAb that recognizes a heterogeneous subdomain of RGI. The mAb, INRA-AGI-1, was produced by immunization of mice with RGI oligosaccharides isolated from potato tubers. These oligomers consisted of highly branched RGI backbones substituted with short side chains. INRA-AGI-1 bound specifically to RGI isolated from galactan-rich cell walls and displayed no binding to other pectic domains. In order to identify its RGI-related epitope, potato RGI oligosaccharides were fractionated by anion-exchange chromatography. Antibody recognition was assessed for each chromatographic fraction. INRA-AGI-1 recognizes a linear chain of (1→4)-linked galactose and (1→5)-linked arabinose residues. By combining the use of INRA-AGI-1 with LM5, LM6 and INRA-RU1 mAbs and enzymatic pre-treatments, evidence is presented of spatial differences in RGI motif distribution within individual cell walls of potato tubers and carrot roots. These observations raise questions about the biosynthesis and assembly of pectin structural domains and their integration and remodeling in cell walls.Eukaryal translation initiation factor 2B (eIF2B) acts as guanine nucleotide exchange factor (GEF) for eIF2 and forms a central target for pathways regulating global protein synthesis. eIF2B consists of five non-identical subunits (α-ϵ), which assemble into a catalytic subcomplex (γ, ϵ) responsible for the GEF activity, and a regulatory subcomplex (α, β, δ) which regulates the GEF activity under stress conditions. Here, we provide new structural and functional insight into the regulatory subcomplex of eIF2B (eIF2B(RSC)). We report the crystal structures of eIF2Bβ and eIF2Bδ from Chaetomium thermophilum as well as the crystal structure of their tetrameric eIF2B(βδ)2 complex. Combined with mutational and biochemical data, we show that eIF2B(RSC) exists as a hexamer in solution, consisting of two eIF2Bβδ heterodimers and one eIF2Bα2 homodimer, which is homologous to homohexameric ribose 1,5-bisphosphate isomerases. This homology is further substantiated by the finding that eIF2Bα specifically binds AMP and GMP as ligands.