Obsessive–Compulsive Disorder is Characterized by a Lack of Adaptive Coping Rather than an Excess of Maladaptive Coping

The present study aimed to elucidate the profile of coping in patients with obsessive–compulsive disorder (OCD) in order to discern whether the disorder is characterized by an excess of maladaptive coping skills and/or a lack of adaptive coping skills. Sixty individuals with OCD were compared with 110 individuals with depression and 1050 nonclinical controls on the Maladaptive and Adaptive Coping Styles Questionnaire (MAX). Psychopathology was assessed with the Obsessive–Compulsive Inventory-Revised (OCI-R), the Yale-Brown Obsessive–Compulsive Scale (Y-BOCS), and the Patient Health Questionnaire-9 for depression (PHQ-9). Individuals with OCD and depression displayed more maladaptive coping and avoidance as well as less adaptive coping than nonclinical controls. Importantly, adaptive coping was significantly lower in individuals with OCD than in those with depression at a medium effect size, whereas the clinical groups were indistinguishable on maladaptive coping and avoidance. Lack of adaptive coping was strongly correlated with resistance to symptoms and poor insight in OCD (Y-BOCS), even after controlling for depression. Lack of adaptive coping skills may represent a specific pathogenetic factor in OCD. Longitudinal studies need to clarify whether strengthening adaptive skills during childhood and adolescence may help to prevent the progression from subclinical to manifest OCD.     

Proposed criteria for mixed-dust pneumoconiosis: definition, descriptions, and guidelines for pathologic diagnosis and clinical correlation

We defined mixed-dust pneumoconiosis (MDP) pathologically as a pneumoconiosis showing dust macules or mixed-dust fibrotic nodules (MDF), with or without silicotic nodules (SN), in an individual with a history of exposure to mixed dust. We defined the latter arbitrarily as a mixture of crystalline silica and nonfibrous silicates. According to our definition of MDP, therefore, MDF should outnumber SN in the lung to make a pathologic diagnosis of MDP. In the absence of confirmation of exposure, mineralogic analyses can be used to support the pathologic diagnosis. The clinical diagnosis of MDP requires the exclusion of other well-defined pneumoconioses, including asbestosis, coal workers’ pneumoconiosis, silicosis, hematite miners’ pneumoconiosis, welders’ pneumoconiosis, berylliosis, hard metal disease, silicate pneumoconiosis, diatomaceous earth pneumoconiosis, carborundum pneumoconiosis, and corundum pneumoconiosis. Typical occupations associated with the diagnosis of MDP include metal miners, quarry workers, foundry workers, pottery and ceramics workers, and stonemasons. Irregular opacities are the major radiographic findings in MDP (ILO 1980), in contrast to silicosis, in which small rounded opacities predominate. Clinical symptoms of MDP are nonspecific. MDP must be distinguished from a variety of nonoccupational interstitial pulmonary disorders.     

ABCA1 and atherosclerosis

ATP binding cassette transporter A1 (ABCA1) mediates the cellular efflux of phospholipids and cholesterol to lipid-poor apolipoprotein A1 (apoA1) and plays a significant role in high density lipoprotein (HDL) metabolism. ABCA1's role in the causation of Tangier disease, characterized by absent HDL and premature atherosclerosis, has implicated this transporter and its regulators liver-X-receptoralpha (LXRalpha) and peroxisome proliferator activated receptorgamma (PPARgamma) as new candidates potentially influencing the progression of atherosclerosis. In addition to lipid regulation, these genes are involved in apoptosis and inflammation, processes thought to be central to atherosclerotic plaque progression. A Medline-based review of the literature was carried out. Tangier disease and human heterozygotes with ABCA1 mutations provide good evidence that ABCA1 is a major candidate influencing atherosclerosis. Animal and in vitro experiments suggest that ABCA1 not only mediates cholesterol and phospholipid efflux, but is also involved in the regulation of apoptosis and inflammation. The complex and beneficial interactions between apoA1 and ABCA1 seem to be pivotal for cholesterol efflux. The expression of the ABCA1 is tightly regulated. Furthermore the plaque microenvironment could potentially promote ABCA1 protein degradation thus compromising cholesterol efflux. PPAR-LXR-ABCA1 interactions are integral to cholesterol homeostasis and these nuclear receptors have proven anti-inflammatory and anti-matrix metalloproteinase activity. Therapeutic manipulation of the ABCA1 transporter is feasible using PPAR and LXR agonists. PPAR agonists like glitazones and ABCA1 protein stabilization could potentially modify the clinical progression of atherosclerotic lesions.     

Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas

Homozygous deletion of p16/CDKN2A is the most common genetic abnormality in malignant mesotheliomas. The aim of this study was to determine prognostic significance of p16/CDKN2A loss in malignant pleural mesotheliomas (MPM) as defined by immunohistochemistry and fluorescence in situ hybridization (FISH). High-density tissue microarrays were constructed from archival formalin-fixed paraffin-embedded samples of 48 MPM. Long survival (LS) was defined as survival greater than 3 years from the time of diagnosis, and short survival was defined as less than 3 years from the time of diagnosis. Both loss of p16 protein expression by immunohistochemistry and homozygous deletion of p16 by FISH were associated with adverse prognosis. Female gender, positive p16 immunoexpression, and lack of p16/CDKN2A deletion significantly predicted the survival for the LS group. Statistical analysis showed a very strong correlation of immunohistochemistry and FISH data. Cases positive for p16 immunoexpression and negative for 9p21 deletion showed the best survival time. Our study is the first to demonstrate decreased frequency of homozygous deletion of 9p21 and loss of p16 immunoreactivity in pleural mesotheliomas from patients with long-term survival of greater than 3 years in contrast to patients with rapidly fatal mesotheliomas. A possible implementation of these tests into preoperative prognostication of MPM and therapeutic decisions should be considered.     

Candida krusei, a multidrug-resistant opportunistic fungal pathogen: geographic and temporal trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005

Candida krusei is well known as a fungal pathogen for patients with hematologic malignancies and for transplant recipients. Using the ARTEMIS Antifungal Surveillance Program database, we describe geographic and temporal trends in the isolation of C. krusei from clinical specimens and the in vitro susceptibilities of 3,448 isolates to voriconazole as determined by CLSI (formerly NCCLS) disk diffusion testing. In addition, we report the in vitro susceptibilities of bloodstream infection isolates of C. krusei to amphotericin B (304 isolates), flucytosine (254 isolates), anidulafungin (121 isolates), caspofungin (300 isolates), and micafungin (102 isolates) as determined by CLSI broth microdilution methods. Geographic differences in isolation were apparent; the highest frequency of isolation was seen for the Czech Republic (7.6%) and the lowest for Indonesia, South Korea, and Thailand (0 to 0.3%). Overall, 83% of isolates were susceptible to voriconazole, ranging from 74.8% in Latin America to 92.3% in North America. C. krusei was most commonly isolated from hematology-oncology services, where only 76.7% of isolates were susceptible to voriconazole. There was no evidence of increasing resistance of C. krusei to voriconazole from 2001 to 2005. Decreased susceptibilities to amphotericin B (MIC at which 90% of isolates were inhibited [MIC₉₀], 4 μg/ml) and flucytosine (MIC₉₀, 16 μg/ml) were noted, whereas 100% of isolates were inhibited by ≤2 μg/ml of anidulafungin (MIC₉₀, 0.06 μg/ml), micafungin (MIC₉₀, 0.12 μg/ml) or caspofungin (MIC₉₀, 0.25 μg/ml). C. krusei is an uncommon but multidrug-resistant fungal pathogen. Among the systemically active antifungal agents, the echinocandins appear to be the most active against this important pathogen.