Cognitive distortions and irrational beliefs in post-traumatic stress,anxiety, and depressive disorders

This study examined the validity of PTSD by comparing the dysfunctional cognitions found in a PTSD group, a clinical group (anxiety or depression), and a nonclinical group. Subjects completed the Millon Clinical Multiaxial Inventory-11, the Impact of Event Scale, the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Cognitive Error Questionnaire, and the Survey of Personal Beliefs. Results revealed that PTSD and. clinical groups were significantly more depressed and anxious than nonclinical subjects. Unlike the PTSD group, only the clinical group endorsed more dysfunctional cognitions than the nonclinical group, which supports the uniqueness of the PTSD group as differing cognitively from clinical groups.     

Plasma miRNA-based signatures in CRC screening programs

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607–0.682), 0.670 (0.626–0.714) and 0.682 (0.580–0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most.     

Platelet mitochondrial dysfunction in critically ill patients: comparison between sepsis and cardiogenic shock

IntroductionPlatelet mitochondrial respiratory chain enzymes (that produce energy) are variably inhibited during human sepsis. Whether these changes occur even during other acute critical illness or are associated with impaired platelet aggregation and secretion (that consume energy) is not known. The aims of this study were firstly to compare platelet mitochondrial respiratory chain enzymes activity between patients with sepsis and those with cardiogenic shock, and secondly to study the relationship between platelet mitochondrial respiratory chain enzymes activity and platelet responsiveness to (exogenous) agonists in patients with sepsis.MethodsThis was a prospective, observational, case–control study. Platelets were isolated from venous blood of 16 patients with severe sepsis or septic shock (free from antiplatelet drugs) and 16 others with cardiogenic shock, within 48 hours from admission to Intensive Care. Platelet mitochondrial respiratory chain enzymes activity was measured with spectrophotometry and expressed relative to citrate synthase activity, a marker of mitochondrial density. Platelet aggregation and secretion in response to adenosine di-phosphate (ADP), collagen, U46619 and thrombin receptor activating peptide were measured with lumiaggregometry only in patients with sepsis. In total, 16 healthy volunteers acted as controls for both spectrophotometry and lumiaggregometry.ResultsPlatelets of patients with sepsis or cardiogenic shock similarly had lower mitochondrial nicotinamide adenine dinucleotide dehydrogenase (NADH) (P < 0.001), complex I (P = 0.006), complex I and III (P < 0.001) and complex IV (P < 0.001) activity than those of controls. Platelets of patients with sepsis were generally hypo-responsive to exogenous agonists, both in terms of maximal aggregation (P < 0.001) and secretion (P < 0.05). Lower mitochondrial NADH (R² 0.36; P < 0.001), complex I (R² 0.38; P < 0.001), complex I and III (R² 0.27; P = 0.002) and complex IV (R² 0.43; P < 0.001) activity was associated with lower first wave of aggregation with ADP.ConclusionsSeveral platelet mitochondrial respiratory chain enzymes are similarly inhibited during human sepsis and cardiogenic shock. In patients with sepsis, mitochondrial dysfunction is associated with general platelet hypo-responsiveness to exogenous agonists.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00541827","term_id":"NCT00541827"}}NCT00541827. Registered 8 October 2007.     

Effects of chronic cocaine abuse on memory and learning

Sixteen chronic (M = 5 years) weekly cocaine users who were at least 10 days (M = 20 days) abstinent were compared to age, education, race, and gender matched controls on the California Verbal Learning Test, Wechsler Adult Intelligence Scale-Revised (WAIS-R) Vocabulary, and Block Design. Subjects with developmental disorder, neurological, psychiatric, or other substance abuse history were excluded. Cocaine subjects learned and recalled fewer words than controls, but did not differ on IQ. Results suggested significant residual impairment in verbal learning efficiency subsequent to chronic cocaine use that results from memory storage difficulties rather than attentional impairment or general intellectual reduction. A dose-response relationship is suggested.     

Suture Rupture in Acromioclavicular Joint Dislocations Treated With Flip Buttons

Acute acromioclavicular joint dislocations (ACDs) may be treated arthroscopically with flip buttons. This extra-articular fixation is easy to implant and is well tolerated. Between 2007 and 2009, 20 ACD patients (2 women and 18 men; mean age, 32 years) had surgery by the arthroscopic TightRope technique (Arthrex, Naples, FL). The main complication of this technique that has been reported is the partial loss of reduction at follow-up due to clavicular osteolysis under the superior flip button. We describe 4 cases with loss of reduction due to rupture of the sutures running across the buttons: 2 women with joint hyperlaxity and acute Rockwood grade IV ACD and 2 men, heavy manual workers, with joint hyperlaxity and acute Rockwood grade IV ACD. The use of flip buttons might not be indicated in patients with joint hyperlaxity because they are able to obtain immediate stability only on the vertical plane and not on the horizontal plane. Anteroposterior movements of the acromioclavicular joint might rub the suture against the bone tunnels leading to wear and cutting.     

Multiple mechanisms of telomere maintenance exist and differentially affect clinical outcome in diffuse malignant peritoneal mesothelioma

PURPOSE: This study aims to investigate the prevalence of the two known telomere maintenance mechanisms, telomerase activity (TA) and alternative lengthening of telomeres (ALT), and to assess their prognostic relevance in diffuse malignant peritoneal mesothelioma (DMPM). EXPERIMENTAL DESIGN: In 44 DMPM specimens obtained from 38 patients, TA was determined using the telomeric repeat amplification protocol and ALT was detected by assaying ALT-associated promyelocytic leukemia nuclear bodies. The prognostic significance of telomere maintenance mechanisms was analyzed by Cox regression in the overall series and in a subset of 29 patients who underwent a uniform treatment regimen consisting of cytoreductive surgery and hyperthermic i.p. chemotherapy. RESULTS: Telomere maintenance mechanisms were detectable in 86.4% of DMPM: ALT or TA alone was found in 18.2% or 63.6% of lesions, respectively, whereas two cases (4.6%) were ALT+/TA+. TA and ALT proved to be inversely associated (P = 0.002). In the overall series, TA was prognostic for 4-year relapse (TA+ versus TA-, hazard ratio, 3.30; 95% confidence interval, 1.23-8.86; P = 0.018) and cancer-related death (TA+ versus TA-, hazard ratio, 3.56; 95% confidence interval, 1.03-12.51; P = 0.045), whereas ALT failed to significantly affect clinical outcome. These results held true also in the subset of patients submitted to uniform treatment with cytoreductive surgery and hyperthermic i.p. chemotherapy. CONCLUSIONS: Our results indicate that both known telomere maintenance mechanisms, TA and ALT, are present in DMPM and differentially affect patient prognosis.