Perceptual versus conceptual interference and pattern separation of verbal stimuli in young and older adults

Recently, several studies have strongly suggested that age‐related decline in episodic memory is associated with deficits in hippocampal pattern separation (orthogonalizing overlapping experiences using distinct neural codes). The same studies also link these deficits to neurobiological features such as dentate/CA3 representational rigidity and perforant path loss. This decline in pattern separation is thought to underlie behavioral deficits in discriminating similar stimuli on pictorial tasks. Similar pictorial stimuli invoke interference both in the perceptual and conceptual domains, and do not allow one to be disentangled from another. For example, it is very difficult to design a set of pictorial stimuli that are perceptually similar yet conceptually unrelated. Verbal stimuli, on the other hand, allow experimenters to independently manipulate conceptual and perceptual interference. We tested discrimination on conceptually similar (semantically related) and perceptually similar (phonologically related) verbal stimuli in young (mean age 20) and older adults (mean age 69), and find that older adults are selectively impaired in perceptual pattern separation. This deficit was not secondary to failure in working memory, attention, or visual processing. Based on past studies, we suggest that perceptual discrimination relies on recollection while conceptual discrimination relies more on gist. Our results fit well within the notion that recollection but not familiarity (i.e. gist) is impaired in older adults, and suggests that the impairment observed in pictorial tasks may be driven mostly by failure in perceptual and not conceptual pattern separation. © 2013 Wiley Periodicals, Inc.     

Hypovolemia-induced severe coronary spasm leading to acute myocardial infarction

Acute ST-elevation myocardial infarction (STEMI) is a well recognized manifestation of severe coronary artery spasm. Although there are many recognized triggers, hypovolemia has not been previously described. The present report describes a case of acute STEMI that occurred four days following major colonic surgery in a severely dehydrated patient. Coronary angiography revealed underfilled coronary arteries with severe multifocal spasm, which largely resolved with aggressive fluid repletion and intracoronary nitrate.     

Leptin and regulatory T-lymphocytes in idiopathic pulmonary arterial hypertension

Immune mechanisms and autoimmunity seem to play a significant role in idiopathic pulmonary arterial hypertension (IPAH) pathogenesis and/or progression, but the pathophysiology is still unclear. Recent evidence has demonstrated a detrimental involvement of leptin in promoting various autoimmune diseases by controlling regulatory T-lymphocytes. Despite this knowledge, the role of leptin in IPAH is currently unknown. We hypothesised that leptin, synthesised by dysfunctional pulmonary endothelium, might play a role in the immunopathogenesis of IPAH by regulating circulating regulatory T-lymphocytes function. First, we collected serum and regulatory T-lymphocytes from controls, and IPAH and scleroderma-associated pulmonary arterial hypertension (SSc-PAH) patients; secondly, we recovered tissue samples and cultured endothelial cells after either surgery or transplantation in controls and IPAH patients, respectively. Our findings indicate that serum leptin was higher in IPAH and SSc-PAH patients than controls. Circulating regulatory T-lymphocyte numbers were comparable in all groups, and the percentage of those expressing leptin receptor was higher in IPAH and SSc-PAH compared with controls, whereas their function was reduced in IPAH and SSc-PAH patients compared with controls, in a leptin-dependent manner. Furthermore, endothelial cells from IPAH patients synthesised more leptin than controls. Our data suggest that endothelial-derived leptin may play a role in the immunopathogenesis of IPAH.     

Microscopic diffuse large B-cell lymphoma (DLBCL) occurring in pseudocysts: do these tumors belong to the category of DLBCL associated with chronic inflammation?

We report 2 cases of localized, microscopic diffuse large B-cell lymphoma (DLBCL) that were detected incidentally within pseudocysts. In case 1, the neoplasm was identified within a 26-cm, 860-g adrenal gland pseudocyst. In case 2, the neoplasm was detected within a 9-cm, 90-g paratesticular pseudocyst. In both cases, the neoplastic cells were large, had a nongerminal center B-cell immunophenotype, and were positive for Epstein-Barr virus (EBV)-encoded RNA detected by in situ hybridization. The most appropriate classification of these tumors using current World Health Organization classification is uncertain. The best fit seems to be DLBCL associated with chronic inflammation (DLBCL-CI), defined as DLBCL arising in the context of long-standing chronic inflammation and associated with EBV infection, with the prototype for this category being pyothorax-associated lymphoma. This term has been used by others in the literature for tumors similar to the cases reported here. However, in the 2 cases we report chronic inflammation was not a prominent feature, and the inflammatory cells that were present showed little relationship to the lymphoma cells. The findings in these cases have led us to question the role of chronic inflammation in pathogenesis. Perhaps the closed space of the pseudocyst, by preventing a cytolytic response to EBV-infected cells, results in local immunodeficiency that may be most important for pathogenesis. We also have concerns about using the term DLBCL-CI for these tumors. Perhaps the cases we report and the few other similar cases reported previously deserve their own category in a future version of the World Health Organization classification.     

Effect of stepped care on health outcomes in patients with osteoarthritis: an observational study in Dutch general practice

Background

A stepped care strategy (SCS) to improve adequate healthcare use in patients with osteoarthritis was developed and implemented in a primary care region in the Netherlands.

Aim

To assess the association between care that is in line with the SCS recommendations and health outcomes.

Design and setting

Data were used from a 2-year observational study of 313 patients who had consulted their GP because of osteoarthritis.

Method

Care was considered ‘SCS-consistent’ if all advised modalities of the previous steps of the SCS were offered before more advanced modalities of subsequent steps. Pain and physical function were measured with the Western Ontario and McMaster Universities Osteoarthritis Index (range 0–100); active pain coping with the Pain Coping Inventory (range 10–40); and self-efficacy with the Dutch General Self-Efficacy Scale (range 12–48). Crude and adjusted associations between SCS-consistent care and outcomes were estimated with generalised estimating equations.

Results

No statistically significant differences were found in changes over a 2-year period in pain and physical function between patients who received SCS-inconsistent care (n = 163) and patients who received SCS-consistent care (n = 117). This was also the case after adjusting for possible confounders, that is, −4.3 (95% confidence interval [CI] = −10.3 to 1.7) and −1.9 (95% CI = −7.0 to 3.1), respectively. Furthermore, no differences were found in changes over time between groups in self-efficacy and pain coping.

Conclusion

The results raised several important issues that need to be considered regarding the value of the SCS, such as the reasons that GPs provide SCS-inconsistent care, the long-term effects of the SCS, and the effects on costs and side effects.