The Orthostatic Discriminant and Severity Scale (ODSS): an assessment of orthostatic intolerance

Clinical Autonomic Research - To assess the ability of the Orthostatic Discriminant and Severity Scale (ODSS) to distinguish symptoms of orthostatic intolerance from non-orthostatic symptoms....     

Recall mammography and psychological distress

BackgroundThe aims of this study were (a) to identify psychological distress before and after being diagnosed with or without cancer in women recalled for further investigation because previous screening mammography indicated possible malignancy and (b) to document the willingness to attend and recommend mammography. Study participants included 526 recalled women (82% response) who completed a questionnaire before the recall mammogram and 4 weeks after receiving the result. Psychological distress was measured using the Hospital Anxiety and Depression Scale.ResultsMost subjects were diagnosed without cancer (87.6% false-positive rate). Recall after mammography among women with a false-positive mammogram was associated with transiently increased anxiety and a slight increase in depression. However, the level of anxiety was similar to and the level of depression was lower than in the general female Norwegian population. Women who received a cancer diagnosis had higher levels of anxiety and depression than the general female Norwegian population. Nearly all women (99%) were satisfied with their participation in the screening programme; 94% thought it was important, 98% would attend the next round of screening and 99% would recommend other women to attend.Concluding statementRecall after mammography was associated with transiently increased anxiety. Four weeks after screening, the level of anxiety was the same and depression was lower compared with the general female Norwegian population. The women were almost unanimously satisfied with their participation in the screening, would participate again and would recommend other women to participate.     

Serum amyloid A protein forms a complex with a fragment of apolipoprotein A-I in the domestic blue fox: a protective mechanism against AA amyloidosis?

The spontaneous occurrence of protein AA-type of amyloidosis varies among animal species. As reactive AA-type of amyloidosis has never been detected in the blue fox, we obtained acute phase sera to search for amyloid-protective elements. The purified SAA fraction was characterized by mass and sequence analyses to disclose any unique domains in the amino acid sequence. The data revealed an SAA protein with heterogeneities in several positions, and showed the typical insertion between positions 69 and 70. By comparing the amino acid sequence with that from other mammals, no unique sequence could be observed. However, a C-terminal fragment of apolipoprotein A-I (ApoA-I) was found attached to the SAA. The amino acid sequence of the ApoA-I fragment revealed a partially blocked and ragged N-terminus. A comparison of the amino acid sequence of ApoA-I with that from the dog showed that the ApoA-I fragment started about position 190, had an intact C-terminus, and showed an identical sequence in all positions, except one. Based on the data, we suggest an interaction of the C-terminal fragment of ApoA-I with the SAA protein that inhibits the AA fibrillogenesis in the blue fox.     

Prevalence of sleep disturbance and the association between poor disease control in people with ankylosing spondylitis within the Australian clinical setting (ASLEEP study): a real-world observational study using the OPAL dataset

Clinical Rheumatology - Sleep disturbance and fatigue are commonly reported in ankylosing spondylitis (AS) but specific prevalence and the relationship to disease control are unknown. This...     

Cognitive-behavioral therapy for panic disorder in patients being treated for alcohol dependence: Moderating effects of alcohol outcome expectancies

Anxiety disorders commonly co-occur with alcohol use disorders and reliably mark a poor response to substance abuse treatment. However, treating a co-occurring anxiety disorder does not reliably improve substance abuse treatment outcomes. Failure to account for individual differences in the functional dynamic between anxiety symptoms and drinking behavior might impede the progress and clarity of this research program. For example, while both theory and research point to the moderating role of tension-reduction alcohol outcome expectancies (TR-AOEs) in the association between anxiety symptoms and alcohol use, relevant treatment studies have not typically modeled TR-AOE effects. We examined the impact of a hybrid cognitive-behavioral therapy (H-CBT) treatment for panic disorder (independent variable) on response to a community-based alcohol dependence treatment program (dependent variable) in patients with higher vs. lower TR-AOEs (moderator). The H-CBT treatment was generally effective in relieving participants' panic symptoms relative to controls. However, TR-AOEs interacted with study cohort (H-CBT vs. control) in predicting response to substance abuse treatment. As expected, the H-CBT was most effective in improving alcohol use outcomes among those with the highest TR-AOEs. The study's primary methodological limitations are related to the quasi-experimental design employed.     

Copper-free click chemistry in living animals

Chemical reactions that enable selective biomolecule labeling in living organisms offer a means to probe biological processes in vivo. Very few reactions possess the requisite bioorthogonality, and, among these, only the Staudinger ligation between azides and triarylphosphines has been employed for direct covalent modification of biomolecules with probes in the mouse, an important model organism for studies of human disease. Here we explore an alternative bioorthogonal reaction, the 1,3-dipolar cycloaddition of azides and cyclooctynes, also known as “Cu-free click chemistry,” for labeling biomolecules in live mice. Mice were administered peracetylated N-azidoacetylmannosamine (Ac₄ManNAz) to metabolically label cell-surface sialic acids with azides. After subsequent injection with cyclooctyne reagents, glycoconjugate labeling was observed on isolated splenocytes and in a variety of tissues including the intestines, heart, and liver, with no apparent toxicity. The cyclooctynes tested displayed various labeling efficiencies that likely reflect the combined influence of intrinsic reactivity and bioavailability. These studies establish Cu-free click chemistry as a bioorthogonal reaction that can be executed in the physiologically relevant context of a mouse.     

Fibril protein fragmentation pattern in systemic AL‐amyloidosis

Immunoglobulin light chain (AL)‐amyloidosis was one of the first types of amyloidosis discovered and still little is known about its pathogenic mechanisms. One major obstacle is the very heterogeneous condition; in fact, every patient could be considered to have their own disease since symptoms and outcome vary enormously. The reason for this is not known but intrinsic factors of the immunoglobulin light chain (LC) and the fact that every LC is unique seem to be important. Post‐translational modifications such as glycosylation and proteolysis are most certainly involved. By using western blotting, we studied in detail the proteolytic pattern in six patients with AL‐amyloidosis of kappa type with the aid of three peptide antisera against two domains in the constant segment and one conserved domain in framework 3 of the variable region. Materials from one to five organs were analysed. The result clearly demonstrates that the fragmentation pattern was similar in amyloid of different organs in one patient but differed greatly between patients. Full‐length, N‐, and C‐terminal fragments were detected with the three antisera. The results strongly support the hypothesis that proteolytic cleavage occurs after fibril formation. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Initial validation of symptom scores derived from the orthostatic discriminant and severity scale

Clinical Autonomic Research - To develop a scale to quantify and discriminate orthostatic from non-orthostatic symptoms. In the current study, we present validation and reliability of orthostatic...     

Binding of 125I-labelled fibrin(ogen) fragments to platelets and to immunoprecipitated glycoprotein IIb-IIIa complex

To further investigate which parts of the fibrinogen molecule that are responsible for its binding to the fibrinogen receptor on human platelets, the following approaches were made: The glycoprotein IIb-IIIa complex (the putative fibrinogen receptor) was immunoprecipitated in crossed immunoelectrophoresis of Triton X-100-extracts of platelets against antibodies to whole platelet proteins. Subsequently, the immunoplates were incubated with 125I-labelled, plasmin- or CNBr-cleaved fibrinogen fragments (pre-X,X,Y,D,Degta,Efg,N-DSK) or fibrin fragments (E1,N-dsk), characterized by partial sequenation. The immunoplates were exposed to X-ray films, and binding of the fragments to the glycoprotein IIb-IIIa complex was examined. The findings were compared to the results obtained from studies on binding of the same fragments to intact gel-filtered platelets after ADP-stimulation. The following conclusions were made: All fragments except Efg and Degta bound to the immunoprecipitated GPIIb-IIIa complex as well as to ADP-stimulated platelets suggesting that at least two sequences in the E domain and one in each of the D domains of fibrinogen are involved in binding to the platelet receptor. The GPIIb-IIIa complex is the only surface-located platelet antigen that binds fibrinogen and the aforementioned fragments. The binding of the fragments to the receptor is dependent on divalent cations.