Intra-laboratory analytical variability of biochemical markers of fibrosis (Fibrotest) and activity (Actitest) and reference ranges in healthy blood donors.

Combinations of tests comprising alpha2-macroglobulin, haptoglobin, apolipoprotein Al, gamma-glutamyltransferase, total bilirubin (Fibrotest) and alanine aminotransferase (Actitest) are being developed as alternatives to liver biopsy in patients with chronic hepatitis C. The aim of this study was to assess in the same laboratory the impact of parameter assay variations on Fibrotest and Actitest results and intra-patient reproducibility of the two tests. The stability of the samples for each test was studied after storage at -80 degrees C and -20 degrees C. Within-run, between-run and total imprecision for each parameter assay, and for Fibrotest and Actitest results, were determined. Transferability of assay results between different analyzers was studied. Intra-patient reproducibility was assessed in 55 hospitalized patients. Fibrotest and Actitest reference ranges were determined in 300 blood donors (reference group). The stability of the parameters was affected by serum storage at -20 degrees C only. The impact of parameter analytical variability on Fibrotest and Actitest results was less than 10% and intra-patient reproducibility was acceptable (p > 0.05). The transferability between different analyzers of results of assays performed under the same standardized and calibration conditions was excellent. Fibrotest and Actitest reference ranges in blood donors were (mean+/-SE) 0.075+/-0.004 and 0.068+/-0.004, respectively. The low intra-laboratory and intra-patient variability in Fibrotest and Actitest results confirm Fibrotest and Actitest reliability.     

Blocking protein quality control to counter hereditary cancers

Inhibitors of molecular chaperones and the ubiquitin‐proteasome system have already been clinically implemented to counter certain cancers, including multiple myeloma and mantle cell lymphoma. The efficacy of this treatment relies on genomic alterations in cancer cells causing a proteostatic imbalance, which makes them more dependent on protein quality control (PQC) mechanisms than normal cells. Accordingly, blocking PQC, e.g. by proteasome inhibitors, may cause a lethal proteotoxic crisis in cancer cells, while leaving normal cells unaffected. Evidence, however, suggests that the PQC system operates by following a better‐safe‐than‐sorry principle and is thus prone to target proteins that are only slightly structurally perturbed, but still functional. Accordingly, implementing PQC inhibitors may also, through an entirely different mechanism, hold potential for other cancers. Several inherited cancer susceptibility syndromes, such as Lynch syndrome and von Hippel‐Lindau disease, are caused by missense mutations in tumor suppressor genes, and in some cases, the resulting amino acid substitutions in the encoded proteins cause the cellular PQC system to target them for degradation, although they may still retain function. As a consequence of this over‐meticulous PQC mechanism, the cell may end up with an insufficient amount of the abnormal, but functional, protein, which in turn leads to a loss‐of‐function phenotype and manifestation of the disease. Increasing the amounts of such proteins by stabilizing with chemical chaperones, or by targeting molecular chaperones or the ubiquitin‐proteasome system, may thus avert or delay the disease onset. Here, we review the potential of targeting the PQC system in hereditary cancer susceptibility syndromes.     

Comparative evaluation of synthetic anti-HER2 Affibody molecules site-specifically labelled with <Superscript>111</Superscript>In using N-terminal DOTA,NOTA and NODAGA chelators in mice bearing prostate cancer xenografts

Purpose  

In disseminated prostate cancer, expression of human epidermal growth factor receptor type 2 (HER2) is one of the pathways to androgen independence. Radionuclide molecular imaging of HER2 expression in disseminated prostate cancer might identify patients for HER2-targeted therapy. Affibody molecules are small (7 kDa) targeting proteins with high potential as tracers for radionuclide imaging. The goal of this study was to develop an optimal Affibody-based tracer for visualization of HER2 expression in prostate cancer.     

Motivation,exercise, and stress in breast cancer survivors

Purpose

Reduced stress and reduced risk of cancer recurrence are among the many benefits of physical activity (PA) for cancer survivors. Exercise behaviors are linked to motivational factors. We investigated the associations between motivational profile, self-reported levels of PA and stress, and mental functioning in 94 posttreatment breast cancer survivors who voluntarily enrolled in an exercise program.

Methods

Participants completed the Apter Motivational Style Profile (AMSP), Lifetime of Physical Activity (LTPA) Questionnaire, International Physical Activity Questionnaire (IPAQ), Medical Outcomes Short Form SF-36® (SF-36), and Perceived Stress Scale (PSS) and provided 10 saliva specimens (to measure cortisol levels). PA levels were calculated in metabolic equivalent hours per week (MET-hours/week).

Results

Participants reported high levels of current and historical PA (M?=?39.2 MET-h/week, SD?=?39.7; M?=?14.2 MET-h/week, SD?=?15.4, respectively). They also reported high levels of stress (M?=?33.6, SD?=?4.5) coupled with low mental functionality as measured by SF-36 mental component scale (MCS) (M?=?44.4, SD?=?8.8). PSS was negatively associated with MCS (r?=??0.27, p?=?0.009). Salivary cortisol was not associated with any measure. Participants had a conformist (“follow rules”) and alloic (“about others”) motivational profile. No motivational, exercise history, or stress variables were associated with current PA.

Conclusions

As expected, participants reported higher levels of stress and lower mental functioning. Participants presented a unique motivational profile relative to the general population. Further research into the associations of motivation, exercise behaviors, and stress is warranted.     

Competency Lies in the Eye of the Beholder? Comparing the Interpersonal Skills of Currently, Formerly and Never Depressed Females Using Self and Partner Reports

Research examining the social skills of currently and remitted depressed individuals has yielded inconsistent results. The current study aimed to clarify some of this research by comparing the responses of 58 female partners (10 currently depressed, 23 formerly depressed, and 25 never depressed) to hypothetical marital conflict vignettes. Male partners were also asked to report on how their partners would respond in each of the conflict situations. As anticipated, results indicated that currently and formerly depressed females reported behaviors suggestive of lower competency than did never depressed females. The analysis controlled for female relationship quality. However, the reports of the male partner indicated that men’s relationship quality, rather than female depression status, affected men’s reports of their partner’s competency, such that men who were happier in their relationship reported higher levels of competent behavior in their partners. Our findings provide converging evidence for interpersonal models of depression using standardized measures of social competence and also highlight the importance of taking the quality of the interpersonal relationship into account when testing interpersonal models of depression.     

Laryngeal injuries following endotracheal intubation in ENT surgery: predictive value of anatomical scores

Endotracheal intubation has been associated with a threefold higher incidence of laryngopharyngeal complaints following anesthesia in comparison to laryngeal mask airway. Such complaints, including hoarseness and sore throat, have been reported in up to 90 % of patients within 24 h of extubation. The purpose of this study was to determine which preoperatively documented clinical and anatomic parameters are predictive of laryngo-pharyngeal trauma resulting from elective endotracheal intubation. Fifty-three patients undergoing ENT procedures requiring general anesthesia with endotracheal intubation were recruited. Pre and postoperative laryngostroboscopic examination was performed and findings correlated to preoperative clinical and anatomic parameters. Readily assessed anatomic parameters including height (>180 cm) and weight (>80 kg) correlated significantly to the Eckerbom grade of intubation-associated acute laryngeal injury (rs = 0.374; p = 0.006 and rs = 0.278; p = 0.044, respectively). The mandibular protrusion test also correlated significantly to the Eckerbom grade (rs = 0.462, p = 0.001) while the upper-lip-bite test showed significant correlation to impaired vocal fold oscillation (rs = 0.288, p = 0.036), with injury prediction sensitivities of 37.5 and 39.4 %, respectively. No parameters correlated to subjective complaints (n = 5, 9.2 %). This study provides suggestions on how to improve the classification of intubation-associated laryngeal injuries as well as providing the basis for larger clinical trials in other surgical subspecialties.     

Association between Orthopedic and Dental Findings: What Level of Evidence is Available?

OBJECTIVE: The aim of this systematic review was to provide comprehensive access to and an analysis of the specialist literature published through December 2005 describing a correlation between orthopedic (leg-length inequality, pelvis obliquity, column diseases and head posture) and dental findings (occlusion, mandibular position, temporomandibular joints, masticatory muscles). METHOD: Four medical and dental internet sources (PubMed; Medpilot.de; databases of the Deutsche Arzte-Verlag and Quintessenz-Verlag) were screened for relevant articles using carefully selected retrieval strategies and keywords. Bibliographies of relevant articles were examined for further pertinent publications. All relevant articles were tabulated according to their year of publication, the subject area discussed, and the levels of scientific evidence. RESULTS: Our electronic inquiry yielded 359 relevant articles (electronic search: 195, search in bibliographies: 164), 355 of which could be analyzed. A correlation between dental findings and spinal column diseases was described in 266 articles, head posture in 216, pelvis obliquity in 53, and leg-length inequality in 35 papers. In 131 publications, conclusions were drawn from dental to orthopedic findings, whereas they were drawn from orthopedic to dental findings in 171 articles. The number of relevant articles rose significantly, particularly since the 1980's. Classification in levels of evidence reveals three publications (0.8%) with level II (randomized controlled trials), 63 (17.7%) with level III (experimental studies with no randomization, cohort studies, or case-control studies), 178 (50.1%) with level IV (non-experimental studies, such as cross-sectional trials, case series, case reports), and 111 (31.3%) with level V (narrative review or expert opinion without explicit critical appraisal). CONCLUSIONS: 1) While there is great interest in possible correlations between orthopedic and dental findings in the specialist literature, most publications fail to provide the hard facts and solid evidence characteristic of high-quality research. 2) This literature analysis attests to the importance of searching electronic databases while making the inherent weaknesses of such searches obvious. Manual literature searches remain essential.