Quantification of the spatiotemporal microstructural organization of the human brain association, projection and commissural pathways across the lifespan using diffusion tensor tractography.

Using diffusion tensor tractography, we quantified the microstructural changes in the association, projection, and commissural compact white matter pathways of the human brain over the lifespan in a cohort of healthy right-handed children and adults aged 6-68 years. In both males and females, the diffusion tensor radial diffusivity of the bilateral arcuate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, corticospinal, somatosensory tracts, and the corpus callosum followed a U-curve with advancing age; fractional anisotropy in the same pathways followed an inverted U-curve. Our study provides useful baseline data for the interpretation of data collected from patients

Intravital multiphoton microscopy can model uptake and excretion of fluorescein in hepatic ischemia-reperfusion injury

The liver is important in the biotransformation of various drugs, where hepatic transporters facilitate uptake and excretion. Ischemia-reperfusion (I/R) injury is a common occurrence in liver surgery, and the developing oxidative stress can lead to graft failure. We used intravital multiphoton tomography, with fluorescence lifetime imaging, to characterize metabolic damage associated with hepatic I/R injury and to model the distribution of fluorescein as a measure of liver function. In addition to measuring a significant increase in serum alanine transaminase levels, characteristic of hepatic I/R injury, a decrease in the averaged weighted lifetime of reduced nicotinamide adenine dinucleotide phosphate was observed, which can be attributed to a changed metabolic redox state of the hepatocytes. I/R injury was associated with delayed uptake and excretion of fluorescein and elevated area-under-the-curve within the hepatocytes compared to sham (i.e., untreated control) as visualized and modeled using images recorded by intravital multiphoton tomography. High-performance liquid chromatography analysis showed no differences in plasma or bile concentrations of fluorescein. Finally, altered fluorescein distribution was associated with acute changes in the expression of liver transport proteins. In summary, multiphoton intravital imaging is an effective approach to measure liver function and is more sensitive in contrasting the impact of I/R injury than measuring plasma and bile concentrations of fluorescein

Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats

Ischemia-reperfusion (I/R) injury is a common occurrence in liver surgery. In orthotopic transplantation, the donor liver is exposed to periods of ischemia and when oxygenated blood is reintroduced to the liver, oxidative stress may develop and lead to graft failure. The aim of this project was to investigate whether noninvasive multiphoton and fluorescence lifetime imaging microscopy, without external markers, were useful in detecting early liver damage caused by I/R injury. Localized hepatic ischemia was induced in rats for 1 h followed by 4 h reperfusion. Multiphoton and fluorescence lifetime imaging microscopy was conducted prior to ischemia and up to 4 h of reperfusion and compared to morphological and biochemical assessment of liver damage. Liver function was significantly impaired at 2 and 4 h of reperfusion. Multiphoton microscopy detected liver damage at 1 h of reperfusion, manifested by vacuolated cells and heterogeneous spread of damage over the liver. The damage was mainly localized in the midzonal region of the liver acinus. In addition, fluorescence lifetime imaging showed a decrease in cellular metabolic activity. Multiphoton and fluorescence lifetime imaging microscopy detected evidence of early I/R injury both structurally and functionally. This provides a simple noninvasive technique useful for following progressive liver injury without external markers. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3647597

Validation of EpiTRAQ, a transition readiness assessment tool for adolescents and young adults with epilepsy

ObjectiveTo design and validate a transition readiness assessment tool for adolescents and young adults with epilepsy and without intellectual disability.MethodsWe adapted a general transition readiness assessment tool (TRAQ) to add epilepsy‐relevant items based on concepts in current epilepsy quality measures. The adapted tool, EpiTRAQ, maintained the original structure and scoring system. Concurrent with clinical implementation in pediatric and adult epilepsy clinics at an academic medical center, we assessed the validity and reliability of this adapted tool for patients 16‐26 years of age. This process included initial validation with 302 patients who completed EpiTRAQ between October 2017 and May 2018; repeat validation with 381 patients who completed EpiTRAQ between June 2018 and September 2019; and retest reliability among 153 patients with more than one completed EpiTRAQ.ResultsMean scores were comparable between initial and repeat validation populations (absolute value differences between 0.05 and 0.1); internal consistency ranged from good to high. For both the initial and repeat validation, mean scores and internal consistency demonstrated high comparability to the original TRAQ validation results. Upon retest, few patients rated themselves with a lower score, while the majority rated themselves with higher scores.SignificanceEpiTRAQ is a valid and reliable tool for assessing transition readiness in adolescents and young adults with epilepsy and without intellectual disability.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162789/2/epi412427_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162789/1/epi412427.pd

109th Congress

Environmental protection concerns span a wide variety of issues, including clean air, water quality, chemical security, and environmental aspects of other major issue areas, such as energy, transportation, disaster relief and cleanup, and defense. This report provides an overview of key environmental issues receiving attention in the 109th Congress

Ursinus College Alumni Journal, August 1966

Departure day • Guidance • Counseling Ursinus students • Guiding high school students • Bertolt Brecht in America and East Berlin • From the President • The other side of the desk • Ursinus grizzly leaps the first Alumni Centennial Fund hurdle • A debate on war livens Alumni Day • Ups & downs of progress • Sporting scene: Lacrosse; Top athlete graduates; Wrestling; Tennis; Baseball; Track • Regionals: Each spring meeting has a style of its own • Campus clippings • Class notebook • Weddings • Births • In memoriamhttps://digitalcommons.ursinus.edu/alumnijournal/1086/thumbnail.jp

109th Congress

Environmental protection concerns span a wide variety of issues, including clear air, water quality, chemical security, and environmental aspects of other major issue areas, such as energy, transportation, disaster relief and cleanup, and defense. This report provides an overview of key environmental issues receiving attention in the 109th Congress. A number of environmental measures have been the subject of congressional activity, some of them as part of comprehensive bills and laws on broader subjects such as energy and transportation. Appropriations for the Environmental Protection Agency (EPA) affect many of the programs and issues discussed in this report

The ratio of monocytes to lymphocytes in peripheral blood correlates with increased susceptibility to clinical malaria in Kenyan children.

BACKGROUND: Plasmodium falciparum malaria remains a major cause of illness and death in sub-Saharan Africa. Young children bear the brunt of the disease and though older children and adults suffer relatively fewer clinical attacks, they remain susceptible to asymptomatic P. falciparum infection. A better understanding of the host factors associated with immunity to clinical malaria and the ability to sustain asymptomatic P. falciparum infection will aid the development of improved strategies for disease prevention. METHODS AND FINDINGS: Here we investigate whether full differential blood counts can predict susceptibility to clinical malaria among Kenyan children sampled at five annual cross-sectional surveys. We find that the ratio of monocytes to lymphocytes, measured in peripheral blood at the time of survey, directly correlates with risk of clinical malaria during follow-up. This association is evident among children with asymptomatic P. falciparum infection at the time the cell counts are measured (Hazard ratio (HR)  =  2.7 (95% CI 1.42, 5.01, P  =  0.002) but not in those without detectable parasitaemia (HR  =  1.0 (95% CI 0.74, 1.42, P  =  0.9). CONCLUSIONS: We propose that the monocyte to lymphocyte ratio, which is easily derived from routine full differential blood counts, reflects an individual's capacity to mount an effective immune response to P. falciparum infection

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations