Abnormal bone geometry at the metacarpal bone shaft of rheumatoid arthritis patients with maintained muscle-bone relationship

OBJECTIVES:: Metacarpal juxta-articular bone is altered in Rheumatoid Arthritis (RA). However, a detailed analysis of disease related geometrical adaptations of the metacarpal shaft is missing. The aim of the present study was to assess the role of RA disease, forearm muscle cross-sectional area (CSA), age and sex on bone geometry at the metacarpal shaft. METHODS:: In 64 RA patients and 128 control subjects geometric properties of the third metacarpal bone mid-shaft and forearm muscle CSA were measured by peripheral quantitative computed tomography (pQCT). Linear models were performed for cortical CSA, total bone CSA, polar stress-strain Index (polar SSI, a surrogate for bone's resistance to bending and torsion), cortical thickness and Metacarpal Index (MI=cortical CSA/total CSA) with explanatory variables muscle CSA, age, RA status and sex. RESULTS:: Forearm muscle CSA was associated with cortical and total metacarpal CSA, and polar SSI. RA group status was associated with all bone parameters except cortical CSA. There was a significant interaction between RA status and age, indicating that the RA group had a greater age-related decrease in cortical CSA, cortical thickness and MI. CONCLUSIONS:: Bone geometry of the metacarpal shaft is altered in RA patients compared to healthy controls. While bone mass of the metacarpal shaft is adapted to forearm muscle mass, cortical thickness and MI are reduced but outer bone shaft circumference and polar SSI increased in RA patients. These adaptations correspond to an enhanced aging pattern in RA patients.

[Evaluation of a preschool program to promote phonological awareness and letter-sound correspondence--long-term effects in the prevention of dyslexia at the end of the 3rd and 4th grades]

The present study evaluates the long-term effects of a preschool training in phonological awareness and letter- sound correspondence.

Lateglacial and early Holocene glaciation in the tropical Andes caused by La Niña-like conditions

The response of the tropics to North Atlantic cold events, such as Heinrich Event I (H-I, ∼ 17–15 ka) and the Younger Dryas (YD, 12.7–11.5 ka), is still one of the most tantalizing, yet unresolved issues in paleoclimatology. The advent of surface exposure dating has therefore instigated the establishment of glacial chronologies in the tropical Andes to investigate potential climate teleconnections. Here, we present new exposure ages from the Cordillera Cochabamba (17°17′S), Bolivia, that reveal glacial advances during H-I and YD, as well as during the Early Holocene. Our chronology correlates well with cold sea surface temperatures in the eastern tropical Pacific, which indicates that La Niña-like conditions, i.e. forcings intrinsic to the tropics, played a key role for moisture advection and glaciation in the tropical Andes.

Dendritic spikes in apical dendrites of neocortical layer 2/3 pyramidal neurons

Layer 2/3 (L2/3) pyramidal neurons are the most abundant cells of the neocortex. Despite their key position in the cortical microcircuit, synaptic integration in dendrites of L2/3 neurons is far less understood than in L5 pyramidal cell dendrites, mainly because of the difficulties in obtaining electrical recordings from thin dendrites. Here we directly measured passive and active properties of the apical dendrites of L2/3 neurons in rat brain slices using dual dendritic-somatic patch-clamp recordings and calcium imaging. Unlike L5 cells, L2/3 dendrites displayed little sag in response to long current pulses, which suggests a low density of I(h) in the dendrites and soma. This was also consistent with a slight increase in input resistance with distance from the soma. Brief current injections into the apical dendrite evoked relatively short (half-width 2-4 ms) dendritic spikes that were isolated from the soma for near-threshold currents at sites beyond the middle of the apical dendrite. Regenerative dendritic potentials and large concomitant calcium transients were also elicited by trains of somatic action potentials (APs) above a critical frequency (130 Hz), which was slightly higher than in L5 neurons. Initiation of dendritic spikes was facilitated by backpropagating somatic APs and could cause an additional AP at the soma. As in L5 neurons, we found that distal dendritic calcium transients are sensitive to a long-lasting block by GABAergic inhibition. We conclude that L2/3 pyramidal neurons can generate dendritic spikes, sharing with L5 pyramidal neurons fundamental properties of dendritic excitability and control by inhibition.

Aurora kinases as anticancer drug targets

The human aurora family of serine-threonine kinases comprises three members, which act in concert with many other proteins to control chromosome assembly and segregation during mitosis. Aurora dysfunction can cause aneuploidy, mitotic arrest, and cell death. Aurora kinases are strongly expressed in a broad range of cancer types. Aurora A expression in tumors is often associated with gene amplification, genetic instability, poor histologic differentiation, and poor prognosis. Aurora B is frequently expressed at high levels in a variety of tumors, often coincidently with aurora A, and expression level has also been associated with increased genetic instability and clinical outcome. Further, aurora kinase gene polymorphisms are associated with increased risk or early onset of cancer. The expression of aurora C in cancer is less well studied. In recent years, several small-molecule aurora kinase inhibitors have been developed that exhibit preclinical activity against a wide range of solid tumors. Preliminary clinical data from phase I trials have largely been consistent with cytostatic effects, with disease stabilization as the best response achieved in solid tumors. Objective responses have been noted in leukemia patients, although this might conceivably be due to inhibition of the Abl kinase. Current challenges include the optimization of drug administration, the identification of potential biomarkers of tumor sensitivity, and combination studies with cytotoxic drugs. Here, we summarize the most recent preclinical and clinical data and discuss new directions in the development of aurora kinase inhibitors as antineoplastic agents.

Evaluation of sugar maple dieback in the Upper Great Lakes region and development of a forest health youth education program

Acer saccharum Marsh., is one of the most valuable trees in the northern hardwood forests. Severe dieback was recently reported by area foresters in the western Upper Great Lakes Region. Sugar Maple has had a history of dieback over the last 100 years throughout its range and different variables have been identified as being the predisposing and inciting factors in different regions at different times. Some of the most common factors attributed to previous maple dieback episodes were insect defoliation outbreaks, inadequate precipitation, poor soils, atmospheric deposition, fungal pathogens, poor management, or a combination of these. The current sugar maple dieback was evaluated to determine the etiology, severity, and change in dieback on both industry and public lands. A network of 120 sugar maple health evaluation plots was established in the Upper Peninsula, Michigan, northern Wisconsin, and eastern Minnesota and evaluated annually from 2009-2012. Mean sugar maple crown dieback between 2009-2012 was 12.4% (ranging from 0.8-75.5%) across the region. Overall, during the sampling period, mean dieback decreased by 5% but individual plots and trees continued to decline. Relationships were examined between sugar maple dieback and growth, habitat conditions, ownership, climate, soil, foliage nutrients, and the maple pathogen sapstreak. The only statistically significant factor was found to be a high level of forest floor impacts due to exotic earthworm activity. Sugar maple on soils with lower pH had less earthworm impacts, less dieback, and higher growth rates than those on soils more favorable to earthworms. Nutritional status of foliage and soil was correlated with dieback and growth suggesting perturbation of nutrient cycling may be predisposing or contributing to dieback. The previous winter's snowfall totals, length of stay on the ground, and number of days with freezing temperatures had a significant positive relationship to sugar maple growth rates. Sapstreak disease, Ceratocystis virescens, may be contributing to dieback in some stands but was not related to the amount of dieback in the region. The ultimate goal of this research is to help forest managers in the Great Lakes Region prevent, anticipate, reduce, and/or salvage stands with dieback and loss in the future. An improved understanding of the complex etiology associated with sugar maple dieback in the Upper Great Lakes Region is necessary to make appropriate silvicultural decisions. Forest Health education helps increase awareness and proactive forest management in the face of changing forest ecosystems. Lessons are included to assist educators in incorporating forest health into standard biological disciplines at the secondary school curricula.