Physiological stress in captive Greater rheas (Rhea americana): Highly sensitive plasma corticosterone response to an ACTH challenge

Up to the present no studies have been conducted either on baseline concentrations of adrenal hormones or on hormonal responses to stress in Greater rhea (Rhea americana) and most ratite species. The aims of this work were to assess the presence of corticosterone in plasma of Greater rhea, to validate a corticosterone ¹²⁵I-radioimmunoassay for determining corticosterone levels in plasma samples and to study the activation of the adrenal gland after an adrenocorticotrophic hormone (ACTH) challenge. Six captive Greater rhea juveniles of 10 months of age received an intravenous ACTH injection. Blood samples were taken at 0 min (baseline pre-ACTH levels), and post-injection at 15, 30, 60 min and at 24 and 48 h. The high pressure liquid chromatography (HPLC) analysis of pooled plasma showed that corticosterone is the glucocorticoid found in the plasma of Greater rhea. Biochemical assays of standard validation (e.g., parallelism, exogenous corticosterone recovery) showed that measurements of corticosterone present in the plasma of the Greater rhea provided by commercial corticosterone ¹²⁵I-radioimmunoassay were accurate and precise. ACTH challenge induced a more than 40-fold increase in plasma corticosterone at 60 min post-ACTH (from 4.0 to 166.5 ng/ml, on average). The corticosterone response to ACTH in Greater rhea was higher than is usual in birds, an apparently typical characteristic of ratites.     

Locally Linear Diffeomorphic Metric Embedding (LLDME) for surface-based anatomical shape modeling

This paper presents the algorithm, Locally Linear Diffeomorphic Metric Embedding (LLDME), for constructing efficient and compact representations of surface-based brain shapes whose variations are characterized using Large Deformation Diffeomorphic Metric Mapping (LDDMM). Our hypothesis is that the shape variations in the infinite-dimensional diffeomorphic metric space can be captured by a low-dimensional space. To do so, traditional Locally Linear Embedding (LLE) that reconstructs a data point from its neighbors in Euclidean space is extended to LLDME that requires interpolating a shape from its neighbors in the infinite-dimensional diffeomorphic metric space. This is made possible through the conservation law of momentum derived from LDDMM. It indicates that initial momentum, a linear transformation of the initial velocity of diffeomorphic flows, at a fixed template shape determines the geodesic connecting the template to a subject's shape in the diffeomorphic metric space and becomes the shape signature of an individual subject. This leads to the compact linear representation of the nonlinear diffeomorphisms in terms of the initial momentum. Since the initial momentum is in a linear space, a shape can be approximated by a linear combination of its neighbors in the diffeomorphic metric space. In addition, we provide efficient computations for the metric distance between two shapes through the first order approximation of the geodesic using the initial momentum as well as for the reconstruction of a shape given its low-dimensional Euclidean coordinates using the geodesic shooting with the initial momentum as the initial condition. Experiments are performed on the hippocampal shapes of 302 normal subjects across the whole life span (18-94years). Compared with Principal Component Analysis and ISOMAP, LLDME provides the most compact and efficient representation of the age-related hippocampal shapes. Even though the hippocampal volumes among young adults are as variable as those in older adults, LLDME disentangles the hippocampal local shape variation from the hippocampal size and thus reveals the nonlinear relationship of the hippocampal morphometry with age.     

Plasma transthyretin as a candidate marker for Alzheimer's disease

Diagnosis of the progressive neurodegenerative disorder Alzheimer's disease (AD) can only definitively be made postmortem. The most promising AD biomarkers identified to date are found in cerebrospinal fluid (CSF). Among these, one of the most interesting candidates is transthyretin (TTR), the carrier of thyroxine and retinol, which also binds with amyloid-β (Aβ), and it has been suggested that it protects against Aβ deposition. A biomarker detectable in plasma would have great diagnostic value and could be of use for determining disease progression and the monitoring of therapeutic efficacy due to its greater accessibility over CSF-based markers. We aimed to validate TTR as a prognostic marker in AD and to determine its relation with cognitive measures. We examined the plasma protein levels of TTR in 90 people with late-onset AD and 50 age-matched non-demented controls (NDC) by immunoblotting and found lower plasma TTR levels in AD compared to NDC (p = 0.004). We then quantified plasma TTR by enzyme-linked immunosorbent assays in a larger independent cohort (n = 270) including subjects with mild to severe AD. Plasma TTR levels were significantly lower in AD cases with rapid cognitive decline and with severe cognitive impairment. Regression analyses showed plasma TTR levels also predicted cognitive decline over the ensuing 6 months. These data indicate that plasma TTR is a strong candidate AD biomarker that should be included in the development of blood based biomarker panels for disease diagnosis and also suggests that plasma TTR is a marker of disease severity and progression.     

The symptom burden of primary brain tumors: evidence for a core set of tumor- and treatment-related symptoms

Background

A set of symptoms common across cancers has been proposed to enhance quality of care and clinical research in solid tumor patients. Using data from several clinical studies, this study evaluated these symptoms in primary brain tumor patients.

Methods

Symptom report data using the MD Anderson Symptom Instrument -Brain Tumor (MDASI-BT) from 621 patients enrolled in 8 clinical studies was used. The prevalence and severity of symptoms were reported as they relate to tumor grade, treatment stage and KPS.

Results

The sample was primarily white (82.5%) males (59%) with high-grade gliomas (75%). More than 50% of patients reported at least 10 concurrent symptoms, and 40% of patients reporting having at least 3 moderate-to-severe symptoms. Fatigue, drowsiness, difficulty remembering, disturbed sleep, and distress were the most severe symptoms reported by all tumor grades. Functional interference of symptoms with ability to work, perform activities, walk, and enjoy life was reported by more than 25% of patients.

Conclusions

These results support a core set of symptoms, common in other solid tumor patients, that may impact clinical care and assessment of treatment benefit. Although only 5 of the Center for Medical Technology Policy list of proposed core symptoms met criteria for inclusion in this sample, 5 of the other proposed core symptoms were also reported in similar frequency as reported in the other cancer populations. This primary brain tumor population differed from other solid tumor patients in that other symptoms, which could be disease related, were more prevalent and thus should also be collected for these patients.