Psychosocial predictors of long-term adjustment to lower-limb amputation and phantom limb pain

PURPOSE: To evaluate the utility of a biopsychosocial model to predict long-term adjustment to lower-limb amputation and phantom limb pain (PLP). METHOD: One month after lower-limb amputation, 70 participants completed measures of PLP intensity, cognitions (catastrophizing, perceived control over pain), coping (pain-contingent rest), social environment (social support, solicitous responding), and functioning (pain interference, depressive symptoms). The measures of functioning were administered again at 1- and 2-years post-amputation. Multiple regression analyses were used to examine the ability of the psychosocial variables at 1-month post-amputation to predict changes in the functioning measures over time. RESULTS: The psychosocial variables at 1-month post-amputation, controlling for initial PLP intensity, accounted for 21% of the variance in change in depressive symptoms at 1-year (p < 0.05), and 27% and 22% (p's < 0.01 and 0.05, respectively) of the variance in change in pain interference and depressive symptoms, respectively, at 2-years post-amputation. Catastrophizing and social support were associated with decreases (improvement) in both criterion measures, while solicitous responding was associated with increases (worsening) in both measures. DISCUSSION: The findings support a biopsychosocial model of long-term adjustment to amputation and PLP. In addition, results suggest that some psychosocial variables are more important than others for predicting adjustment, providing important implications for early interventions after amputation.     

Tolerance to self gangliosides is the major factor restricting the antibody response to lipopolysaccharide core oligosaccharides in Campylobacter jejuni strains associated with Guillain-Barré syndrome

Guillain-Barré syndrome following Campylobacter jejuni infection is frequently associated with anti-ganglioside autoantibodies mediated by molecular mimicry with ganglioside-like oligosaccharides on bacterial lipopolysaccharide (LPS). The regulation of antibody responses to these T-cell-independent antigens is poorly understood, and only a minority of Campylobacter-infected individuals develop anti-ganglioside antibodies. This study investigates the response to gangliosides and LPS in strains of mice by using a range of immunization strategies. In normal mice following intraperitoneal immunization, antibody responses to gangliosides and LPS are low level but can be enhanced by the antigen format or coadministration of protein to recruit T-cell help. Class switching from the predominant immunoglobulin M (IgM) response to IgG3 occurs at low levels, suggesting B1-cell involvement. Systemic immunization results in poor responses. In GalNAc transferase knockout mice that lack all complex gangliosides and instead express high levels of GM3 and GD3, generation of anti-ganglioside antibodies upon immunization with either complex gangliosides or ganglioside-mimicking LPS is greatly enhanced and exhibits class switching to T-cell-dependent IgG isotypes and immunological memory, indicating that tolerance to self gangliosides is a major regulatory factor. Responses to GD3 are suppressed in knockout mice compared with wild-type mice, in which responses to GD3 are induced specifically by GD3 and as a result of polyclonal B-cell activation by LPS. The anti-ganglioside response generated in response to LPS is also dependent on the epitope density of the ganglioside mimicked and can be further manipulated by providing secondary signals via lipid A and CD40 ligation.     

Attention to Background Strain Is Essential for Metabolic Research: C57BL/6 and the International Knockout Mouse Consortium

The International Knockout Mouse Consortium (IKMC) introduces its targeted constructs into C57BL/6N embryonic stem cells. However, breeding with a Cre-recombinase and/or Flp-recombinase mouse is required for the generation of a null allele with the IKMC cassette. Many recombinase strains are in the C57BL/6J background, resulting in knockout animals on a mixed strain background. This can lead to variability in metabolic data and the use of improper control groups. While C57BL/6N and C57BL/6J are derived from the same parental C57BL/6 strain, there are key genotypic and phenotypic differences between these substrains. Many researchers may not even be aware of these differences, as the shorthand C57BL/6 is often used to describe both substrains. We found that 58% of articles involving genetically modified mouse models did not completely address background strain. This review will describe these two substrains and highlight the importance of separate consideration in mouse model development. Our aim is to increase awareness of this issue in the diabetes research community and to provide practical strategies to enable researchers to avoid mixed strain animals when using IKMC knockout mice.     

A 10-year Study of the Academic Progress of Students Identified as Low Performers after Their First Semester of Pharmacy School

Objective. To examine whether pharmacy students characterized as low performers at the conclusion of their first semester remained low performers throughout their academic career.Methods. Bottom quartile performance on first semester grade point average (GPA) was compared to licensing examination success, cumulative grade point average at the end of the didactic education and whether the student graduated on time, using cross tabulation analysis. Relative risk ratios and confidence intervals were calculated.Results. Students in the bottom quartile for GPA at the end of their first semester in pharmacy school were approximately six times more likely not to graduate on time, not to pass the North American Pharmacist Licensure Exam on their first attempt and to remain in the bottom quartile for GPA at the end of their didactic education.Conclusion. This study suggests that pharmacy students who score in the bottom quartile for GPA at the end of their first semester are more likely to underperform academically unless they take corrective action.     

Hippocampus-specific fMRI group activation analysis using the continuous medial representation

We present a new shape-based approach for regional group activation analysis in fMRI studies. The method restricts anatomical normalization, spatial smoothing and random effects statistical analysis to the space inside and around a structure of interest. Normalization involves finding intersubject correspondences between manually outlined masks, and it leverages the continuous medial representation, which makes it possible to extend surface-based shape correspondences to the space inside and outside of structures. Our approach is an alternative to whole-brain normalization in cases where the latter may fail due to anatomical variability or pathology. It also provides an opportunity to analyze the shape and thickness of structures concurrently with functional activation. We apply the technique to the hippocampus and evaluate it using data from a visual scene encoding fMRI study, where activation in the hippocampus is expected. We produce detailed statistical maps of hippocampal activation, as well as maps comparing activation inside and outside of the hippocampus. We find that random effects statistics computed by the new approach are more significant than those produced using the Statistical Parametric Mapping framework (Friston, K.J., Holmes, A.P., Worsley, K.J., Poline, J.-P., Firth, C.D., Frackowiak, R.S.J. 1994, Statistical parametric maps in functional imaging: a general linear approach. Human Brain Mapping, 2(4): 189-210) at low levels of smoothing, suggesting that greater specificity can be achieved by the new method without a severe tradeoff in sensitivity.