Personal relative deprivation associated with functional disorders via stress: An examination of fibromyalgia and gastrointestinal symptoms.

BACKGROUND: Personal relative deprivation is a negative social comparison process typified by self-comparison, negative appraisal, and resultant negative emotionality. Personal relative deprivation has been associated with poorer physical and mental health in several domains. It has been hypothesized that the deprivation-health link operates through a stress pathway. Stress has been specifically implicated in the onset and maintenance of functional disorders, including fibromyalgia and functional gastrointestinal disorders. Despite the theoretical links between personal deprivation, stress, and functional disorders, researchers have not assessed relationships between these variables. METHODS: We recruited community participants (n = 517; 54.9% female) to examine whether personal relative deprivation can account for variance in fibromyalgia and functional gastrointestinal symptoms beyond known demographic correlates of physical health. We also examined whether the relationships between personal relative deprivation and functional disorder symptoms are mediated by stress. RESULTS: Consistent with our hypotheses, personal relative deprivation accounted for symptom variance in fibromyalgia and functional gastrointestinal disorders beyond that accounted for by demographic variables alone. Further, self-reported stress was found to mediate relationships between personal relative deprivation and fibromyalgia and gastrointestinal symptoms. CONCLUSIONS: The current results support biopsychosocial models of physical health and suggest that, for patients presenting with functional disorders symptoms, a combination of biological and psychosocial interventions may be warranted.

Can radiological changes in lymph node volume during treatment predict success of radiation therapy in patients with locally advanced head and neck squamous cell carcinoma?

BACKGROUND: Assessment of nodal response after radiotherapy (RT) for head and neck squamous cell carcinoma is difficult, as both CT and positron emission tomography scanning have limited predictive value for residual disease. We sought to measure changes in nodal volume during RT to determine whether such changes are predictive of nodal disease control. METHODS: Patients with locally advanced head and neck squamous cell carcinoma treated with 70 Gy of radical RT (±chemotherapy or anti-epidermal growth factor receptor (EGFR) antibodies) were eligible. Baseline pre-RT scans and cone-beam CT scans done at the outset of treatment and at weeks 3, 5 and 7 (cone-beam CTs # 1, 2, 3 and 4, respectively) were deformably coregistered, and 3D nodal volumes were measured. RESULTS: Thirty-eight eligible patients were identified. The main primary tumour site was oropharyngeal; most patients had stage IVa disease. Twenty-seven patients received concurrent platinum-based chemotherapy, 10 received only an EGFR inhibitor with RT and one received RT alone. Twelve patients had a failure in the neck. After week 1 of treatment, a 4% mean decrease in nodal volume was observed, increasing to 40% at week 7. Platinum-based chemotherapy achieved significantly greater decreases in nodal volume than EGFR inhibitors (44 vs. 25%; P = 0.026). Advanced tumour stage predicted neck failure (P = 0.002), but nodal volumes did not correlate with neck control. CONCLUSIONS: Changes in nodal volume are minimal initially during RT but accelerate during the latter weeks of therapy. This study suggests that chemotherapy achieves a greater decrease in nodal volume than EGFR inhibitors and that nodal changes do not predict disease control in the neck.

Increased prion protein processing and expression of metabotropic glutamate receptor 1 in a mouse model of Alzheimer's disease.

Prion protein (PrP(C) ), a glycosylphosphatidylinositol-anchored protein corrupted in prion diseases, has been shown recently to interact with group I metabotropic glutamate receptors (mGluRs). Moreover, both PrP(C) and mGluRs were proposed to function as putative receptors for ß-amyloid in Alzheimer's disease. PrP(C) can be processed in neurons via α or ß-cleavage to produce PrP(C) fragments that are neuroprotective or toxic, respectively. We found PrP(C) α-cleavage to be 2-3 times higher in the cortex of APPswe/PS1dE9 mice, a mouse model of Alzheimer's disease. A similar age-dependent increase was observed for PrP(C) ß-cleavage. Moreover, we observed considerable age-dependent increase in cortical expression of mGluR1, but not mGluR5. Exposure of cortical neuronal cultures to ß-amyloid oligomers upregulated mGluR1 and PrP(C) α-cleavage, while activation of group I mGluRs increased PrP(C) shedding from the membrane, likely due to increased levels of a disintegrin and metalloprotease10, a key disintegrin for PrP(C) shedding. Interestingly, a similar increase in a disintegrin and metalloprotease10 was detected in the cortex of 9-month-old APPswe/PS1dE9 animals. Our experiments reveal novel and complex processing of PrP(C) in connection with mGluR overexpression that seems to be triggered by ß-amyloid peptides. Prion protein (PrP(C) ) and metabotropic glutamate receptors (mGluR) are implicated in Alzheimer's disease (AD). We found age-dependent increase in PrP(C) processing, ADAM10 and mGluR1 levels in AD mouse model. These changes could be reproduced in cultured cortical neurons treated with Aß peptide. Our findings suggest that increased levels of Aß can trigger compensatory responses that may affect neuronal toxicity.