A Bifactor and item response analysis of the geriatric anxiety inventory.

BACKGROUND: Due to previously reported mixed findings, there is a need for further empirical research on the factorial structure of the commonly used Geriatric Anxiety Inventory (GAI). Therefore, the psychometric properties of the GAI and its short form version (GAI-SF) were evaluated in a psychogeriatric mixed in-and-out patient sample (n = 543). METHODS: Unidimensionality was tested using a bifactor analysis. Rasch modeling was used to assess scale properties. Sex, cognitive functioning and depressive symptoms were tested for differential item functioning (DIF). RESULTS: The bifactor analysis identified an essential unidimensional (general) factor structure but also specific local factors. The general factor comprises all the 20 items as one factor, and the results showed that the variance in the general and specific factors (subscale) scores is best explained by the single general factor. These findings were demonstrated for both versions of the GAI. Furthermore, the Rasch models identified extensive item overlap, indicating redundant items in the full version of the GAI. The GAI-SF also seems to extract much of the same information as the full form. Test scores and items have the same meaning for older adults across different demographic status. CONCLUSION: The findings support the use of a total sum score for both GAI and GAI-SF. Notably, when using the GAI-SF, no information is lost, in comparison with the full scale, thus, supporting the option of choosing the short form (version) when considered most appropriate in demanding clinical contexts.

Spatial auditory regularity encoding and prediction: Human middle-latency and long-latency auditory evoked potentials.

By encoding acoustic regularities present in the environment, the human brain can generate predictions of what is likely to occur next. Recent studies suggest that deviations from encoded regularities are detected within 10-50ms after stimulus onset, as indicated by electrophysiological effects in the middle latency response (MLR) range. This is upstream of previously known long-latency (LLR) signatures of deviance detection such as the mismatch negativity (MMN) component. In the present study, we created predictable and unpredictable contexts to investigate MLR and LLR signatures of the encoding of spatial auditory regularities and the generation of predictions from these regularities. Chirps were monaurally delivered in an either regular (predictable: left-right-left-right) or a random (unpredictable left/right alternation or repetition) manner. Occasional stimulus omissions occurred in both types of sequences. Results showed that the Na component (peaking at 34ms after stimulus onset) was attenuated for regular relative to random chirps, albeit no differences were observed for stimulus omission responses in the same latency range. In the LLR range, larger chirp-and omission-evoked responses were elicited for the regular than for the random condition, and predictability effects were more prominent over the right hemisphere. We discuss our findings in the framework of a hierarchical organization of spatial regularity encoding. This article is part of a Special Issue entitled SI: Prediction and Attention.

Event-related potential correlates of sound organization: early sensory and late cognitive effects.

We tested whether incoming sounds are processed differently depending on how the preceding sound sequence has been interpreted by the brain. Sequences of a regularly repeating three-tone pattern, the perceived organization of which spontaneously switched back and forth between two alternative interpretations, were delivered to listeners. Occasionally, a regular tone was exchanged for a slightly or moderately lower one (deviants). The electroencephalogram (EEG) was recorded while listeners continuously marked their perception of the sound sequence. We found that for both the regular and the deviant tones, the early exogenous P1 and N1 amplitudes varied together with the perceived sound organization. Percept-dependent effects on the late endogenous N2 and P3a amplitudes were only found for deviant tones. These results suggest that the perceived sound organization affects sound processing both by modulating what information is extracted from incoming sounds as well as by influencing how deviant sound events are evaluated for further processing.

Involuntary attentional capture by speech and non-speech deviations: a combined behavioral-event-related potential study.

This study applied an auditory distraction paradigm to investigate involuntary attention effects of unexpected deviations in speech and non-speech sounds on behavior (increase in response time and error rate) and event-related brain potentials (ΔN1/MMN and P3a). Our aim was to systematically compare identical speech sounds with physical vs. linguistic deviations and identical deviations (pitch) with speech vs. non-speech sounds in the same set of healthy volunteers. Sine tones and bi-syllabic pseudo-words were presented in a 2-alternative forced-choice paradigm with occasional phoneme deviants in pseudo-words, pitch deviants in pseudo-words, or pitch deviants in tones. Deviance-related ERP components were elicited in all conditions. Deviance-related negativities (ΔN1/MMN) differed in scalp distribution between phoneme and pitch deviants within phonemes, indicating that auditory deviance-detection partly operates in a deviance-specific manner. P3a as an indicator of attentional orienting was similar in all conditions, and was accompanied by behavioral indicators of distraction. Yet smaller behavioral effects and prolonged relative MMN-P3a latency were observed for pitch deviants within phonemes relative to the other two conditions. This suggests that the similarity and separability of task-relevant and task-irrelevant information is essential for the extent of attentional capture and distraction.

Laparoscopic colonic surgery in Denmark 2004-2007.

OBJECTIVE: Laparoscopic colonic surgery was introduced about 15 years ago and has together with the evidence-based 'fast-track' methodology improved early postoperative outcome. The purpose of this study was to asses the organization and early outcome after laparoscopic colonic surgery in Denmark from 2004 to 2007. METHOD: Based upon the National Patient Register, all laparoscopic colonic operations performed in Denmark between January 2004 and December 2006 were analysed regarding number of hospital departments and procedures, hospital stay, readmissions and mortality. RESULTS: One thousand one hundred and forty-nine laparoscopic colonic resections without simultaneous stoma formation were performed in the study period. Twenty-five departments performed the procedures but only four departments performed more than 100 procedures. The median length of primary stay was 4 days (mean 7.7 days). One hundred and twenty-five (10.9%) patients were re-admitted within 30 days and total length of stay (primary plus readmissions) was a median of 5 days (mean 8.5 days). Thirty-day mortality was 2.6% and hospital mortality 3.5%. CONCLUSION: This nationwide study has shown an increased implementation of laparoscopic colonic surgery but probably performed in too many low volume departments. Laparoscopic colonic surgery should be monitored and further advances secured by adjustment of perioperative care to fast-track care.

Organisation and early outcomes of major upper gastrointestinal cancer surgery in Denmark 1996-2004.

BACKGROUND: To assess the relationship between hospital volume and early postoperative outcome the incidence and early outcome of all esophagectomies, pancreaticoduodenectomies and gastric resections in Denmark from 1996 to 2004 was described. METHODS: The National Patient Registry and discharge information from all hospital departments were analysed for all the operations due to a malignant diagnosis. All information was examined for postoperative length of stay and hospital mortality. RESULTS: During the study period 26 departments performed at least one esophageal resection, 13 departments performed at least one Whipple procedure and 37 departments performed at least one gastric resection. Four departments performed more than 20 esophageal resections per year, whereas one department performed more than 20 Whipple procedures and one more than 20 gastric resections per year. The overall mean length of stay was 21.6 days, 24 days and 18 days for esophageal, pancreatic and gastric resections, respectively, with no difference between high and low volume departments. The hospital mortality was 8.6%, 8.9% and 8.2%, respectively. CONCLUSION: The overall high mortality and long postoperative stay in patients undergoing upper gastrointestinal cancer surgery in Denmark calls for improvement by regionalisation into 3-4 departments and monitoring of results.

Enhanced activity of osteoblast differentiation factor (PEBP2alphaA2/CBFa1) in affected sutural osteoblasts from patients with nonsyndromic craniosynostosis.

OBJECTIVE: Nonsyndromic craniosynostosis is characterized by premature closure of one or more cranial sutures in infants. The purpose of this investigation was to evaluate cellular and molecular events that lead to pathogenesis of nonsyndromic craniosynostosis. DESIGN: This study utilized discarded samples of normal and affected cranial sutures from 12 patients (7 boys, 5 girls) with nonsyndromic craniosynostosis. RESULTS: Histological evaluation of affected sutures revealed complete osseous obliteration instead of a zone of connective tissue and osteogenic cells as seen in normal sutures. Although proliferation of normal and affected osteoblasts did not vary substantially, elevated osteocalcin production and increased in vitro bone nodule formation indicated that the differentiation and the bone-forming potential of affected osteoblasts was significantly higher than that of normal cells. We therefore investigated the levels and activity of Cbfa1, a transcription factor that plays an integral role in osteoblast differentiation. Northern blot analysis of messenger RNA from both normal and affected sutural osteoblasts revealed a twofold increase in the expression of Cbfa1 in affected cells. This increase in the level of Cbfa1 transcript correlated with an increase in its transcriptional activity on the osteocalcin gene promoter, as assessed using gene transfer methods. CONCLUSION: Our results indicated that osteoblasts from synostosed sutures exhibit an increased potential for differentiation and bone formation. The increased level and activity of Cbfa1 could play a vital role in the aberrant function of these affected osteoblasts and may explain their altered behavior compared to the normal cells.

Androgens suppress osteoclast formation induced by RANKL and macrophage-colony stimulating factor.

Androgen deficiency in males leads to an increase in osteoclastic bone resorption and a progressive decrease in bone mineral density. In the current studies, we examined the ability of 5 alpha-dihydrotestosterone to suppress osteoclast formation induced by receptor activator of NF-kB ligand (RANKL) and macrophage-colony stimulating factor in vitro. 5 alpha-Dihydrotestosterone suppressed the differentiation of bone marrow monocytes into osteoclasts from both sham-operated and orchidectomized mice. Androgen deficiency also led to an increase in the number of hematopoietic precursors capable of forming osteoclasts and increased the relative responsiveness of these cells to androgens in vitro. Interestingly, E2 was as effective as 5 alpha-dihydrotestosterone in suppressing osteoclast formation in bone marrow monocytes from both sham and orchidectomized mice. As with bone marrow monocytes, 5 alpha-dihydrotestosterone also suppressed RANKL-induced osteoclast formation in the monocyte-macrophagic cell line RAW264.7. In RAW264.7 cells, androgens appear to block RANKL-induced osteoclast formation through selective regulation of c-JUN: Accordingly, 5 alpha-dihydrotestosterone suppressed RANKL-induced c-Jun N-terminal kinase activation and reduced c-Jun expression levels. These effects resulted in a reduction in RANKL-induced activator protein-1 DNA binding activity and a corresponding suppression in activator protein-1-mediated transcriptional activation. These studies indicate that both E and androgens can suppress osteoclast formation via a direct, stromal cell-independent action on osteoclast precursors to block key transcription factors such as c-Jun essential for osteoclast differentiation.

IL-4 inhibits osteoclast formation through a direct action on osteoclast precursors via peroxisome proliferator-activated receptor gamma 1.

IL-4 is a pleiotropic immune cytokine secreted by activated T(H)2 cells that inhibits bone resorption both in vitro and in vivo. The cellular targets of IL-4 action as well as its intracellular mechanism of action remain to be determined. We show here that IL-4 inhibits receptor activator of NF-kappaB ligand-induced osteoclast differentiation through an action on osteoclast precursors that is independent of stromal cells. Interestingly, this inhibitory effect can be mimicked by both natural as well as synthetic peroxisome proliferator-activated receptor gamma1 (PPARgamma1) ligands and can be blocked by the irreversible PPARgamma antagonist GW 9662. These findings suggest that the actions of IL-4 on osteoclast differentiation are mediated by PPARgamma1, an interpretation strengthened by the observation that IL-4 can activate a PPARgamma1-sensitive luciferase reporter gene in RAW264.7 cells. We also show that inhibitors of enzymes such as 12/15-lipoxygenase and the cyclooxygenases that produce known PPARgamma1 ligands do not abrogate the IL-4 effect. These findings, together with the observation that bone marrow cells from 12/15-lipoxygenase-deficient mice retain sensitivity to IL-4, suggest that the cytokine may induce novel PPARgamma1 ligands. Our results reveal that PPARgamma1 plays an important role in the suppression of osteoclast formation by IL-4 and may explain the beneficial effects of the thiazolidinedione class of PPARgamma1 ligands on bone loss in diabetic patients.

Estrogens suppress RANK ligand-induced osteoclast differentiation via a stromal cell independent mechanism involving c-Jun repression.

Loss of ovarian function following menopause results in a substantial increase in bone turnover and a critical imbalance between bone formation and resorption. This imbalance leads to a progressive loss of trabecular bone mass and eventually osteoporosis, in part the result of increased osteoclastogenesis. Enhanced formation of functional osteoclasts appears to be the result of increased elaboration by support cells of osteoclastogenic cytokines such as IL-1, tumor necrosis factor, and IL-6, all of which are negatively regulated by estrogens. We show here that estrogen can suppress receptor activator of NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF)-induced differentiation of myelomonocytic precursors into multinucleated tartrate-resistant acid phosphatase-positive osteoclasts through an estrogen receptor-dependent mechanism that does not require mediation by stromal cells. This suppression is dose-dependent, isomer-specific, and reversed by ICI 182780. Furthermore, the bone-sparing analogues tamoxifen and raloxifene mimic estrogen's effects. Estrogen blocks RANKL/M-CSF-induced activator protein-1-dependent transcription, likely through direct regulation of c-Jun activity. This effect is the result of a classical nuclear activity by estrogen receptor to regulate both c-Jun expression and its phosphorylation by c-Jun N-terminal kinase. Our results suggest that estrogen modulates osteoclast formation both by down-regulating the expression of osteoclastogenic cytokines from supportive cells and by directly suppressing RANKL-induced osteoclast differentiation.

Identification of the poly(C) binding protein in the complex associated with the 3' untranslated region of erythropoietin messenger RNA.

Hypoxia regulates expression of erythropoietin (EPO), a glycoprotein that stimulates erythrocytosis, at the level of transcription and also possibly at the level of messenger RNA (mRNA) stability. A pyrimidine-rich region within the EPO mRNA 3' untranslated region was implicated in regulation of EPO mRNA stability element and shown to bind protein factors. In the present study we wished to identify the protein factor binding to the pyrimidine-rich sequence in the EPO mRNA stability element. Using mobility shift assays, ultraviolet light cross-linking, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and electroelution of protein factors from the gel slices corresponding to the ribonucleoprotein complexes, we found that two isoforms of a 40 kD poly(C) binding protein (PCBP, also known as alphaCP or hnRNPE), PCBP1, and PCBP2 are present in that complex. In Hep3B or HepG2 cells hypoxia induces neither expression of PCBP nor formation of the ribonucleoprotein complex associated with EPO mRNA that involves PCBP.