bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypothalamic-pituitary-adrenal axis response in borderline personality disorder without post-traumatic features
Authors: Carrasco Jose L. , Díaz-Marsá Marina , Pastrana Jose I. , Molina Rosa , Brotons Loreto , López-Ibor María I. , López-Ibor Juan J.
Published: March 2007

Hypothalamic–pituitary–adrenal (HPA) axis sensitivity was investigated in 32 non-medicated patients with borderline personality disorder without comorbid post-traumatic syndromes and in 18 normal individuals using a modified dexamethasone suppression test (0.25 mg). Enhanced cortisol suppression was found in the patients v. controls (P < 0.05) and the percentage of participant's with non-suppression was smaller in the patient (34%) than in the control group (89%) (P < 0.01). Baseline cortisol levels in the patients were also lower than in the controls (P < 0.05). The 0.25 mg dexamethasone suppression test reveals increased feedback inhibition of the HPA in borderline personality disorder.
Can deficits in social problem-solving in people with personality disorder be reversed?
Authors: Crawford M. J.
Published: March 2007

Research evidence is beginning to emerge that social problem-solving can improve the social functioning of people with personality disorder. This approach is particularly important because it may be relatively easy to train healthcare workers to deliver this intervention. However, the costs and cost-effectiveness of social problem-solving need to be established if it is to be made more widely available.
Management of insomnia in older adults
Authors: Sivertsen Børge , Nordhus Inger Hilde
Published: March 2007

Complaints of insomnia are very common, especially in older adults. Although pharmacotherapy is the most common form of treatment, recent evidence shows cognitive–behavioural therapy to be superior in the short- and long-term management of insomnia. Low-threshold intervention programmes may reduce both the individual and societal burden of insomnia, coexisting with or without other mental or physical disorders.
The Research on Community Consultation: An Annotated Bibliography
Authors: Baren Jill M. , Biros Michelle H.
Published: March 2007

Community consultation is a required element of research studies that use a waiver of or exception from informed consent. Its intent is to provide an additional patient safeguard in emergency research circumstances when prospective informed consent is not possible. Investigators have reported that community consultation may be the most difficult aspect in implementing research trials using a wavier of or exception from informed consent. This article presents a brief overview of the sparse literature available on the process of community consultation since the inception of the current emergency research regulations. To determine if the process is meeting its goals, more research will be required.
Chemoradiation Followed by Surgery Compared With Chemoradiation Alone in Squamous Cancer of the Esophagus: FFCD 9102
Authors: Bedenne Laurent , Michel Pierre , Bouché Olivier , Milan Chantal , Mariette Christophe , Conroy Thierry , Pezet Denis , Roullet Bernard , Seitz Jean-François , Herr Jean-Philippe , Paillot Bernard , Arveux Patrick , Bonnetain Franck , Binquet Christine
Published: March 2007

Purpose

Uncontrolled studies suggest that chemoradiation has similar efficacy as surgery for esophageal cancer. Therefore, a randomized trial was carried out to compare, in responders only, chemoradiation alone with chemoradiation followed by surgery in patients with locally advanced tumors.

Patients and Methods

Eligible patients had operable T3N0-1M0 thoracic esophageal cancer. Patients received two cycles of fluorouracil (FU) and cisplatin (days 1 to 5 and 22 to 26) and either conventional (46 Gy in 4.5 weeks) or split-course (15 Gy, days 1 to 5 and 22 to 26) concomitant radiotherapy. Patients with response and no contraindication to either treatment were randomly assigned to surgery (arm A) or continuation of chemoradiation (arm B; three cycles of FU/cisplatin and either conventional [20 Gy] or split-course [15 Gy] radiotherapy). Chemoradiation was considered equivalent to surgery if the difference in 2-year survival rate was less than 10%.

Results

Of 444 eligible patients, 259 were randomly assigned; 230 patients (88.8%) had epidermoid cancer, and 29 (11.2%) had glandular carcinoma. Two-year survival rate was 34% in arm A versus 40% in arm B (hazard ratio for arm B v arm A = 0.90; adjusted P = .44). Median survival time was 17.7 months in arm A compared with 19.3 months in arm B. Two-year local control rate was 66.4% in arm A compared with 57.0% in arm B, and stents were less required in the surgery arm (5% in arm A v 32% in arm B; P < .001). The 3-month mortality rate was 9.3% in arm A compared with 0.8% in arm B (P = .002). Cumulative hospital stay was 68 days in arm A compared with 52 days in arm B (P = .02).

Conclusion

Our data suggest that, in patients with locally advanced thoracic esophageal cancers, especially epidermoid, who respond to chemoradiation, there is no benefit for the addition of surgery after chemoradiation compared with the continuation of additional chemoradiation.
Impact of Delirium on Cognition, Distress, and Health-Related Quality of Life After Hematopoietic Stem-Cell Transplantation
Authors: Fann Jesse R. , Alfano Catherine M. , Roth-Roemer Sari , Katon Wayne J. , Syrjala Karen L.
Published: March 2007

Purpose

To determine the impact of delirium during the acute phase of myeloablative hematopoietic stem-cell transplantation (HSCT) on health-related quality of life (HRQOL), distress, and neurocognitive functioning 30 and 80 days after transplantation.

Patients and Methods

Ninety patients completed a battery assessing HRQOL, distress, and neuropsychological functioning before receiving their first HSCT. Delirium was assessed three times per week using the Delirium Rating Scale and the Memorial Delirium Assessment Scale from 7 days before transplantation through 30 days after transplantation. At 30 days after transplantation, distress and neurocognitive functioning were assessed. At 80 days after transplantation, HRQOL, distress, and neuropsychological functioning were re-evaluated.

Results

After adjusting for confounding factors, patients who experienced a delirium episode, versus patients who did not, reported significantly worse depression, anxiety, and fatigue symptoms at 30 days (linear regression βs = 0.2, 0.3, and 0.5, respectively; P < .04). At 80 days, patients with a delirium episode had significantly worse executive functioning (β = −1.1; P < .02), attention and processing speed (βs = −4.7 and −5.4, respectively; P < .03), mental health on the Medical Outcomes Study Health Survey, 12-item short form (β = −6.5; P < .02), and anxiety, fatigue, and cancer and treatment distress symptoms (βs = 0.4, 0.6, and 0.3, respectively; P < .03).

Conclusion

Patients with a malignancy who experience delirium during myeloablative HSCT showed impaired neurocognitive abilities and persistent distress 80 days after transplantation. Effective prevention or treatment of delirium during HSCT may improve both cognitive and psychological outcomes.
Early Changes in Auditory Function As a Result of Platinum Chemotherapy: Use of Extended High-Frequency Audiometry and Evoked Distortion Product Otoacoustic Emissions
Authors: Knight Kristin R. , Kraemer Dale F. , Winter Christiane , Neuwelt Edward A.
Published: March 2007

Purpose

The objective is to describe progressive changes in hearing and cochlear function in children and adolescents treated with platinum-based chemotherapy and to begin preliminary evaluation of the feasibility of extended high-frequency audiometry and distortion product otoacoustic emissions for ototoxicity monitoring in children.

Patients and Methods

Baseline and serial measurement of conventional pure-tone audiometry (0.5 to 8 kHz) and evoked distortion product otoacoustic emissions (DPOAEs) were conducted for 32 patients age 8 months to 20 years who were treated with cisplatin and/or carboplatin chemotherapy. Seventeen children also had baseline and serial measurement of extended high-frequency (EHF) audiometry (9 to 16 kHz). Audiologic data were analyzed to determine the incidence of ototoxicity using the American Speech-Language-Hearing Association criteria, and the relationships between the different measures of ototoxicity.

Results

Of the 32 children, 20 (62.5%) acquired bilateral ototoxicity in the conventional frequency range during chemotherapy treatment, and 26 (81.3%) had bilateral decreases in DPOAE amplitudes and dynamic range. Of the 17 children with EHF audiometry results, 16 (94.1%) had bilateral ototoxicity in the EHF range. Pilot data suggest that EHF thresholds and DPOAEs show ototoxic changes before hearing loss is detected by conventional audiometry.

Conclusion

EHF audiometry and DPOAEs have the potential to reveal earlier changes in auditory function than conventional frequency audiometry during platinum chemotherapy in children.
Pharmacogenetic Profiling in Patients With Advanced Colorectal Cancer Treated With First-Line FOLFOX-4 Chemotherapy
Authors: Ruzzo Annamaria , Graziano Francesco , Loupakis Fotios , Rulli Eliana , Canestrari Emanuele , Santini Daniele , Catalano Vincenzo , Ficarelli Rita , Maltese Paolo , Bisonni Renato , Masi Gianluca , Schiavon Gaia , Giordani Paolo , Giustini Lucio , Falcone Alfredo , Tonini Giuseppe , Silva Rosarita , Mattioli Rodolfo , Floriani Irene , Magnani Mauro
Published: March 2007

Purpose

The objective is to investigate whether polymorphisms with putative influence on fluorouracil/oxaliplatin activity are associated with clinical outcomes of patients with advanced colorectal cancer treated with first-line oxaliplatin, folinic acid, and fluorouracil palliative chemotherapy.

Materials and Methods

Consecutive patients were prospectively enrolled onto medical oncology units in Central Italy. Patients were required to have cytologically/histologically confirmed metastatic disease with at least one measurable lesion. Peripheral blood samples were used for genotyping 12 polymorphisms in thymidylate synthase, methylenetetrahydrofolate reductase, xeroderma pigmentosum group D (XPD), excision repair cross complementing group 1 (ERCC1), x-ray cross complementing group 1, x-ray cross complementing protein 3, glutathione S-transferases (GSTs) genes. The primary end point of the study was to investigate the association between genotypes and progression-free survival (PFS).

Results

In 166 patients, ERCC1-118 T/T, XPD-751 A/C, and XPD-751 C/C genotypes were independently associated with adverse PFS. The presence of two risk genotypes (ERCC1-118 T/T combined with either XPD-751 A/C or XPD-751 C/C) occurred in 50 patients (31%). This profiling showed an independent role for unfavorable PFS with a hazard ratio of 2.84% and 95% CI of 1.47 to 5.45 (P = .002). Neurotoxicity was significantly associated with GSTP1-105 A/G. Carriers of the GSTP1-105 G/G genotype were more prone to suffer from grade 3 neurotoxicity than carriers of GSTP1-105 A/G and GSTP1-105 A/A genotypes.

Conclusion

A pharmacogenetic approach may be an innovative strategy for optimizing palliative chemotherapy in patients with advanced colorectal cancer. These findings deserve confirmation in additional prospective studies.
Patient Assessment of Bowel Function During and After Pelvic Radiotherapy: Results of a Prospective Phase III North Central Cancer Treatment Group Clinical Trial
Authors: Haddock Michael G. , Sloan Jeff A. , Bollinger John W. , Soori Gamini , Steen Preston D. , Martenson James A.
Published: March 2007

Purpose

To evaluate patient assessment of long-term effect of pelvic radiotherapy on bowel function.

Patients and Methods

As part of a prospective randomized trial evaluating the impact of sucralfate on bowel function in patients receiving pelvic radiotherapy, patient-assessed bowel function data were collected during radiotherapy and again at 4 weeks and 1 year after completion of radiotherapy.

Results

The number of bowel movements per day increased up to week 4 and then slowly decreased. At 1 year, the mean number of bowel movements per day had increased from 1.75 to 2.09 and the median from 1 to 2. All measures of adverse bowel function worsened during radiotherapy. Frequency of bowel movements and symptoms of frequency, nocturnal bowel movements, cramping, and bleeding returned close to baseline values by 1 year. Symptoms of urgency, clustering, and measures of incontinence were all persistent at 1 year. The mean increase in bowel function score at 1 year was 0.74 (range, −5 to 7).

Conclusion

Pelvic radiotherapy is associated with a slight increase in bowel movement frequency and decrease in several patient-reported measures of adverse bowel function. Several measures of adverse function persisted at 1 year.
Treatment Tolerance and Efficacy in Geriatric Oncology: A Systematic Review of Phase III Randomized Trials Conducted by Five National Cancer Institute–Sponsored Cooperative Groups
Authors: Kumar Ambuj , Soares Heloisa P. , Balducci Lodovico , Djulbegovic Benjamin
Published: March 2007

Purpose

Elderly patients share the majority of the disease burden in cancer. Although 61% of new cancer cases occur among elderly, they comprise only 25% of the patients enrolled onto randomized clinical trials (RCTs). A systematic review to assess the accurate participation of elderly patients in RCTs has not been performed.

Patients and Methods

We reviewed all consecutively completed phase III RCTs conducted by five National Cancer Institute–sponsored cooperative groups. Published papers and study protocols were used for data extraction. We used a cutoff age of ≥ 65 years to define elderly patients. For trials that did not exclusively enroll elderly, data were extracted on number of participants ≥ 65 years of age. Outcome between the innovative and the standard treatment was compared.

Results

Of 345 studies, only one trial exclusively enrolled elderly patients (0.28%); 57% of the trials (n = 197) had no stratification by age, and 12% of the studies had a stratification age ≥ 65 years (n = 42). Overall survival in the trial exclusively enrolling elderly favored the newer treatments (hazard ratio [HR], 0.69; 95% CI, 0.47 to 1.02; P = .06). Additionally, in trials enrolling more than 40% of elderly, survival and event-free survival favored the innovative treatments (HR for survival, 0.91; 95% CI, 0.84 to 0.99; P = .03; HR for event-free survival, 0.85; 95% CI, 0.72 to 1.01; P = .07). Treatment-related mortality was similar in both the innovative and standard treatment groups (HR, 0.91; 95% CI, 0.47 to 1.78; P = .8).

Conclusion

Our data indicate that enrollment of elderly in experimental RCTs is not associated with increased harm to this patient population. Increased participation of elderly may help in finding new treatments that are clinically applicable specifically to this cohort of patients.
The Genetics of Low-Density Lipoprotein Receptor-Related Protein 5 in Bone: A Story of Extremes
Authors: Balemans Wendy , Van Hul Wim
Published: March 2007

A few years ago, human genetic studies provided compelling evidence that the low-density lipoprotein receptor-related protein 5 (LRP5) is involved in the regulation of bone homeostasis because pathogenic LRP5 mutations were found in monogenic conditions with abnormal bone density. On the one hand, the osteoporosis pseudoglioma syndrome results from loss of function of LRP5, whereas on the other hand, gain-of-function mutations in LRP5 cause conditions with an increased bone density. On the molecular level, these types of mutations result in disturbed (respectively, decreased and increased) canonical Wnt signaling, an important metabolic pathway in osteoblasts during embryonic and postnatal osteogenesis. This signaling cascade is activated by binding of Wnt ligand to the Frizzled/LRP5 receptor complex. In addition to the involvement of LRP5 in conditions with extreme bone phenotypes, the genetic profile of this gene has also been shown to contribute to the determination of bone density in the general population. Quite a number of studies already demonstrated that common polymorphic variants in LRP5 are associated with bone mineral density and consequently osteoporosis, a multifactorial trait with low bone mass and porous bone structure. These genetic studies together with results obtained from in vitro and in vivo studies emphasize the importance of LRP5 and canonical Wnt signaling in the regulation of bone homeostasis. Therefore, unraveling the exact mechanisms of this signaling cascade has become an important area in bone research. This review focuses on the genetics of LRP5 and summarizes the findings on monogenic bone conditions as well as the current knowledge of its involvement in the pathogenesis of osteoporosis.
In Vivo Analysis of Wnt Signaling in Bone
Authors: Glass Donald A. , Karsenty Gerard
Published: March 2007

Bone remodeling requires osteoblasts and osteoclasts working in concert to maintain a constant bone mass. The dysregulation of signaling pathways that affect osteoblast or osteoclast differentiation or function leads to either osteopenia or high bone mass. The discovery that activating and inactivating mutations in low-density lipoprotein receptor-related protein 5, a putative Wnt coreceptor, led to high bone mass and low bone mass in human beings, respectively, generated a tremendous amount of interest in the possible role of the Wnt signaling pathway in the regulation of bone remodeling. A number of mouse models have been generated to study a collection of Wnt signaling molecules that have been identified as regulators of bone mass. These mouse models help establish the canonical Wnt signaling pathway as a major regulator of chondrogenesis, osteoblastogenesis, and osteoclastogenesis. This review will summarize these advances.
Splice Variants of the CYP27b1 Gene and the Regulation of 1,25-Dihydroxyvitamin D3 Production
Authors: Wu S. , Ren S. , Nguyen L. , Adams J. S. , Hewison M.
Published: March 2007

The cytochrome P450 25-hydroxyvitamin D3-1α-hydroxylase (CYP27b1) plays a pivotal role in vitamin D physiology by catalyzing synthesis of active 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. In common with other P450s, CYP27b1 is known to exhibit alternative splicing. Here we have cloned and sequenced several novel intron 2-containing, noncoding splice variant mRNAs for CYP27b1 in 1,25(OH)2D3-producing HKC-8 human proximal tubule and THP-1 monocytic cells. Regulation of 1,25(OH)2D3 synthesis in these cell lines by calciotropic and noncalciotropic factors was associated with altered expression of the CYP27b1 splice variants. To assess the functional significance of this, HKC-8 cells were transfected with short hairpin RNA (shRNA) to inhibit mRNAs containing sequences from intron 2. This resulted in a significant increase in the expression of CYP27b1 protein and synthesis of 1,25(OH)2D3 by HKC-8 cells compared with control cells for two different intron 2-containing shRNAs (both P < 0.001). shRNA to intron 2 had no significant effect on the levels of wild-type CYP27b1 mRNA, suggesting a posttranscriptional mechanism of action. By contrast, shRNA to wild-type CYP27b1 suppressed transcription and activity of the enzyme by 70 and 31%, respectively (both P < 0.01). These data indicate that noncoding splice variants of CYP27b1 are functionally active and may play a significant role in the regulation of 1,25(OH)2D3 synthesis during normal physiology.
Ectopic Expression of Myostatin Induces Atrophy of Adult Skeletal Muscle by Decreasing Muscle Gene Expression
Authors: Durieux Anne-Cécile , Amirouche Adel , Banzet Sébastien , Koulmann Nathalie , Bonnefoy Régis , Pasdeloup Marielle , Mouret Catherine , Bigard Xavier , Peinnequin André , Freyssenet Damien
Published: March 2007

Myostatin is a master regulator of myogenesis and early postnatal skeletal muscle growth. However, myostatin has been also involved in several forms of muscle wasting in adulthood, suggesting a functional role for myostatin in the regulation of skeletal muscle mass in adult. In the present study, localized ectopic expression of myostatin was achieved by gene electrotransfer of a myostatin expression vector into the tibialis anterior muscle of adult Sprague Dawley male rats. The corresponding empty vector was electrotransfected in contralateral muscle. Ectopic myostatin mRNA was abundantly present in muscles electrotransfected with myostatin expression vector, whereas it was undetectable in contralateral muscles. Overexpression of myostatin elicited a significant decrease in muscle mass (10 and 20% reduction 7 and 14 d after gene electrotransfer, respectively), muscle fiber cross-sectional area (15 and 30% reduction 7 and 14 d after gene electrotransfer, respectively), and muscle protein content (20% reduction). No decrease in fiber number was observed. Overexpression of myostatin markedly decreased the expression of muscle structural genes (myosin heavy chain IIb, troponin I, and desmin) and the expression of myogenic transcription factors (MyoD and myogenin). Incidentally, mRNA level of caveolin-3 and peroxisome proliferator activated receptor γ coactivator-1α was also significantly decreased 14 d after myostatin gene electrotransfer. To conclude, our study demonstrates that myostatin-induced muscle atrophy elicits the down-regulation of muscle-specific gene expression. Our observations support an important role for myostatin in muscle atrophy in physiological and physiopathological situations where myostatin expression is induced.
Prognostic Value of Cardiac Troponin T Is Independent of Inflammation, Residual Renal Function, and Cardiac Hypertrophy and Dysfunction in Peritoneal Dialysis Patients
Authors: Yee-Moon Wang Angela , Wai-Kei Lam Christopher , Wang Mei , Hiu-Shuen Chan Iris , Goggins William B , Yu Cheuk-Man , Lui Siu-Fai , Sanderson John E
Published: March 2007

Background: We investigated whether cardiac troponin T (cTnT) independently predicted outcome and added prognostic value over other clinical risk predictors in chronic peritoneal dialysis (PD) with end-stage renal disease.

Methods: Baseline cTnT, echocardiography, indices of dialysis adequacy, and biochemical characteristics were assessed in 238 chronic PD patients who were followed prospectively for 3 years or until death.

Results: Using multivariable Cox regression analysis, cTnT remained predictive of all-cause mortality [hazard ratio 4.43, 95% CI 1.87–10.45, P = 0.001], cardiovascular death (4.12, 1.29–13.17, P = 0.017), noncardiovascular death (8.06, 1.86–35.03, P = 0.005), and fatal and nonfatal cardiovascular events (CVEs) (3.59, 1.48–8.70, P = 0.005) independent of background coronary artery disease, inflammation, residual renal function, left ventricular hypertrophy, and systolic dysfunction. cTnT alone had better predictive value than C-reactive protein (CRP) alone for mortality [area under the ROC curve (AUC) 0.774 vs 0.691; P = 0.089] and first CVE (AUC 0.711 vs 0.593; P = 0.009) at 3 years. Survival models including age, sex, and clinical, biochemical, and echocardiographic characteristics yielded AUCs of 0.813 (95% CI, 0.748–0.877), 0.800 (95% CI, 0.726–0.874), and 0.769 (95% CI, 0.708–0.830), respectively, in relation to all-cause mortality, cardiovascular death, and fatal and nonfatal cardiovascular events. After addition of cTnT, AUCs of the above models increased significantly to 0.832 (95% CI, 0.669–0.894; P = 0.0037), 0.810 (95% CI, 0.739–0.883; P = 0.0036), and 0.780 (95% CI, 0.720–0.840; P = 0.0002), respectively; no AUCs increased when CRP was added.

Conclusions: cTnT is an independent predictor of long-term mortality, cardiovascular death and events, and noncardiovascular death in PD patients.
Suppression of Prepotent Motor Responses Implicate Frontostriatal Dysfunction in Schizophrenia and Its Subtypes
Authors: Oram Joanne , Geffen Gina M.
Published: March 2007

Schizophrenia has been identified as a disorder of the frontostriatal system with impairments in both sustained and selective attention (Bradshaw, 2001). The Sustained Attention to Response Task (SART), which required occasional withholding of an ongoing frequent response when a specified digit occurred, was completed by patients with a clinical diagnosis of schizophrenia (N = 52) and matched controls (N = 46). Relative to controls, participants with schizophrenia responded less frequently and made more impulsive errors. Their correct responses were slower on average, with greater variability in timing. Speed of response was unrelated to neuroleptic medication dosage. The slow responses exhibited by patients with schizophrenia were interpreted as reflecting primarily motor frontostriatal circuit dysfunction, and dysfunction of the lateral orbitofrontal/anterior cingulate circuit is implicated in poor impulse control. To address the heterogeneity of symptoms in schizophrenia, symptom dimension scores (positive, negative and disorganised) were used to determine whether symptom dimensions were associated with differential performance on the SART. Higher negative symptoms were related to increased miss errors on the SART whereas higher disorganised and positive symptom scores were unrelated to performance on this measure. An association between negative symptoms and increased miss errors may be considered indicative of dysfunction of the anterior cingulate circuit, considered to be linked to response inattention, apathy, reduced initiative and focused attention. Implications of this research for understanding the neuroanatomical basis for schizophrenia and its subtypes are discussed.
Anosmia After Traumatic Brain Injury: A Clinical Update
Authors: Drummond Melanie , Douglas Jacinta , Olver John
Published: March 2007

Most people only recognise the value of olfactory function after it is lost. In the context of traumatic brain injury with its far-reaching physical, cognitive, behavioural and emotional sequelae, posttraumatic olfactory dysfunction is an additional consequence that many survivors have to face as they adjust to a changed life situation. The aim of this article is to provide an update on posttraumatic anosmia for clinicians working in the area of brain injury rehabilitation. Brief reviews of incidence studies and causal mechanisms of olfactory impairment after brain injury are provided. Consequences of anosmia in the domains of safety, eating, personal hygiene, leisure, work and relationships with associated adaptive strategies are described.
Differences in Risk Factors for Suicidality Between African American and White Patients Vulnerable to Suicide
Authors: Vanderwerker Lauren C. , Chen Joyce H. , Charpentier Peter , Paulk Mary Elizabeth , Michalski Marion , Prigerson Holly G.
Published: March 2007

Risk factors for suicidal ideation and attempts have been shown to differ between African Americans and Whites across the lifespan. In the present study, risk factors for suicidality were examined separately by race/ethnicity in a population of 131 older adult patients considered vulnerable to suicide due to substance abuse and/or medical frailty. In adjusted analyses, social support was significantly associated with suicidality in African American patients, while younger age and the presence of an anxiety disorder were significantly associated with suicidality in White patients. The results suggest that race/ethnicity–specific risk profiles may improve the detection of suicidality in vulnerable populations.
Performance of the CES‐D and its Short Forms in Screening Suicidality and Hopelessness in the Community
Authors: Cheung Yin Bun , Liu Ka Yuet , Yip Paul S.F.
Published: March 2007

A measurement scale should be short and quick to complete if it is to be practically useful. Drawing on data from a community‐based survey of 2,178 people in Hong Kong, we compared five short forms (5‐ to 10‐item) and the original version (20‐item) of the Center for Epidemiologic Studies–Depression Scale (CES‐D; Radloff, 1977) in predicting suicidal attempts and suicidal thoughts. Short forms with as few as nine items performed in ways very similar to the full version; a version with only five items had a detectable difference from the full version. Sensitivity, specificity, and predictive values in differentiating people with and without suicidal thought or attempt change almost linearly with the cut‐offs.
Surface‐Enhanced Vibrational Spectroscopy: SERS and SEIRA
Authors: Futamata Masayuki
Published: March 2007

With respect to the origin of single‐molecule sensitivity in surface‐enhanced Raman scattering, elastic scattering and emission spectra were investigated for Ag particles adsorbed with dye. The scattering peak observed at 600–650 nm was extinguished during the inactivation process of an enormous SERS signal, whereas localized surface plasmon (LSP) peaks located at 520 nm and 730 nm did not change significantly. The scattering peak at 600–650 nm arises from increased electromagnetic coupling between the LSP of adjacent Ag particles through dye molecules. In addition, distinct emission peaks were observed at 550–600 nm and 600–750 nm for hot Ag particles with adsorbates. These bands were attributed to emissive relaxation of metal electrons and fluorescence of molecules, respectively. Furthermore, the shorter wavelength peak showed invariant Stokes shift irrespective of excitation wavelengths, most probably arising from inelastic scattering of excited electrons by adsorbed molecules.

The adsorbed state of CO and related species on the Pt film electrode was investigated using attenuated total reflection—surface‐enhanced infrared absorption spectroscopy. Intermediate species were found on the bare Pt surface in 1 mM CH3OH + HClO4 solutions at +0.2 V ≤ E ≤ +0.6 V that give absorption peaks at 1405 cm−1 and 1300 cm−1. These bands can be attributed to carbonate species or ‐COH. Water molecules located at the hydrophobic interfaces between CO and electrolyte solutions were evidenced by a quite high OH stretch absorption at 3664–3646 cm−1, as well as a lower broad peak at ca. 3480 cm−1.
Surface‐Enhanced Raman Scattering (SERS) of Microorganisms
Authors: Zeiri Leila , Efrima Shlomo
Published: March 2007

Normal Raman (NR) spectra and surface‐enhanced Raman scattering (SERS) spectra were obtained for the bacterium Escherichia coli and were compared with those of two other microorganisms, Haloferax volcanii and Thiobacillus neapolitanus. It was found that at 514 nm the SERS of E. coli was similar to that of flavin adenine dinucleotide (FAD). Upon increasing the excitation wavelength, contributions from other cell components became evident, and they were attributed to nicotinamide adenine dinucleotide (NAD) or other adenine‐containing molecules in the bacterium. A comprehensive study of FAD, riboflavin (RF), NAD, and adenine under various experimental conditions was thus performed to shed light on the features in the SERS obtained for E. coli. Comparison of NR and SERS measurements of the various samples enabled a better understanding of the SERS spectra and their sensitivity to the specific experimental conditions (excess metal ion concentration and laser excitation wavelengths and intensity). It was concluded that SERS is a highly sensitive technique and that careful examination of the spectra can provide important chemical information.
Coactivator-mediated estrogen response in human squamous cell carcinoma lines
Authors: Ku Tony K S , Crowe David L
Published: March 2007

Steroid hormones such as 17β-estradiol (E2) are critical to diverse cellular processes including tumorigenesis. A number of cofactors such as nuclear receptor corepressor (NCoR), CREB-binding protein (CBP), and steroid receptor coactivator 1 (SRC-1) interact with estrogen receptors (ERs) to regulate transcriptional repression or activation of target genes. Estrogen signaling in non-reproductive tract tissues such as skin is less well characterized and the effectiveness of anti-estrogen therapy for cancer arising from these tissues is unknown. We show that tamoxifen (TAM) treatment inhibited cell cycle progression and proliferation of human cancer lines derived from stratified squamous epithelium squamous cell carcinoma (SCC). E2 had no effect on proliferation of these lines despite low levels of ERα expression. The E2 treatment promoted displacement of the NCoR from ERα and recruitment of CBP to the receptor. SRC-1 expression was not detected in these SCC lines; however, transient transfection of SRC-1, CBP, or both coactivators enhanced transactivation of an estrogen responsive promoter in cancer cells treated with E2 or TAM. In stable clones expressing SRC-1, the coactivator was recruited to ERα along with CBP in E2 but not in TAM-treated cells. SRC-1 expression restored the E2-mediated proliferative response to human SCC lines. This increased proliferation correlated with increased extracellular signal regulated kinase 1 (ERK1) expression. SRC-1 and CBP were recruited to the proximal ERK1 promoter region in E2 but not in TAM-treated cells. We concluded that SRC-1 was a key molecular determinant of estrogen-mediated proliferation in human SCC lines.
Protection of pancreatic β-cells by exendin-4 may involve the reduction of endoplasmic reticulum stress; in vivo and in vitro studies
Authors: Tsunekawa Shin , Yamamoto Naoki , Tsukamoto Katsura , Itoh Yuji , Kaneko Yukiko , Kimura Toshihide , Ariyoshi Yoh , Miura Yoshitaka , Oiso Yutaka , Niki Ichiro
Published: March 2007

The aim of this study was to investigate the in vivo and in vitro effects of exendin-4, a potent glucagon-like peptide 1 agonist, on the protection of the pancreatic β-cells against their cell death. In in vivo experiments, we used β-cell-specific calmodulin-overexpressing mice where massive apoptosis takes place in their β-cells, and we examined the effects of chronic treatment with exendin-4. Chronic and s.c. administration of exendin-4 reduced hyperglycemia. The treatment caused significant increases of the insulin contents of the pancreas and islets, and retained the insulin-positive area. Dispersed transgenic islet cells lived only shortly, and several endoplasmic reticulum (ER) stress-related molecules such as immunoglobulin-binding protein (Bip), inositol-requiring enzyme-1α, X-box-binding protein-1 (XBP-1), RNA-activated protein kinase-like endoplasmic reticulum kinase, activating transcription factor-4, and C/EBP-homologous protein (CHOP) were more expressed in the transgenic islets. We also found that the spliced form of XBP-1, a marker of ER stress, was also increased in β-cell-specific calmodulin-overexpressing transgenic islets. In the quantitative real-time PCR analyses, the expression levels of Bip and CHOP were reduced in the islets from the transgenic mice treated with exendin-4. These findings suggest that excess of ER stress occurs in the transgenic β-cells, and the suppression of ER stress and resultant protection against cell death may be involved in the anti-diabetic effects of exendin-4.
Expression of the oxytocin gene, but not the vasopressin gene, in the rat uterus during pregnancy: influence of oestradiol and progesterone
Authors: Bossmar T , Osman N , Zilahi E , Haj M A El , Nowotny N , Conlon J M
Published: March 2007

Oxytocin (OT) and vasopressin (VP) are neurohypophyseal hormones with potent stimulatory actions on the uterus. In order to determine whether these hormones may have a paracrine action on the uterus, OT and VP gene expression was studied in myometrium from pregnant rats at gestational ages of 14 and 20 days, and from ovariectomized animals treated with oestradiol and progesterone. OTand VP mRNA concentrations were measured using real-time quantitative reverse transcription-PCR, and OT- and VP-like immunoreactivities were determined using RIA. OT mRNA was detected in the uterus from pregnant rats, but did not differ between the groups of different gestational ages. Oestradiol significantly (P<0.05) stimulated OT gene expression in ovariectomized rats. Progesterone alone was without effect on OT mRNA concentrations, but significantly (P<0.05) reduced the oestradiol-induced OT mRNA accumulation. The OT-like immunoreactivity in an extract of myometrium from pregnant rats was eluted from a reverse-phase HPLC column with a retention time identical to that of synthetic OT. Neither VP mRNA nor VP-like immunoreactivity was detected in the myometrium from pregnant or ovariectomized rats. The study demonstrates steroid-dependent expression of the OT gene in the rat uterus and processing of uterine preprooxytocin to the mature nonapeptide. The data support the theory that this peptide may act in a paracrine pathway. No evidence was found for the presence of VP in the uterus so that, if the hormone is involved in a stimulatory action on this tissue, it probably acts via an endocrine mechanism.
Osteopontin deficiency enhances anabolic action of EP4 agonist at a sub-optimal dose in bone
Authors: Kato Norihiko , Kitahara Keiichiro , Rittling Susan R , Nakashima Kazuhisa , Denhardt David T , Kurosawa Hisashi , Ezura Yoichi , Noda Masaki
Published: March 2007

Osteoporosis is one of the most widespread and destructive bone diseases in our modern world. There is a great need for anabolic agents for bone which could reverse this disease, but few are available for clinical use. Prostaglandin E receptor (EP4) agonist (EP4A) is one of the very few anabolic agents for bone in rat, but its systemic efficacy against bone loss at sub-optimal dose is limited in mice. As osteoblasts are regulated by extracellular matrix proteins, we tested whether deficiency of osteopontin (OPN), a secreted phosphorylated protein, could modulate the effects of EP4A (ONO-AE1-329) treatment at 30 μg/kg body weight, a sub-optimal dose, for 5 days/week for 4 weeks. OPN deficiency enhanced the anabolic effects of EP4A on bone volume. Histomorphometric analysis indicated that EP4A increased mineral apposition rate as well as bone formation rate in OPN-deficient but not in wild-type mice. Neither OPN deficiency nor EP4A altered osteoclast parameters. Importantly, OPN deficiency enhanced the direct anabolic action of EP4A locally injected onto the parietal bone in inducing new bone formation. Combination of OPN deficiency and EP4A treatment caused an increase in mineralized nodule formation in the cultures of bone marrow cells. Finally, OPN deficiency enhanced anabolic action of EP4A in the mice subjected to ovariectomy. These data indicate that OPN deficiency enhances the actions of EP4A at sub-optimal dose.
Effects of the CRF1 receptor antagonist SSR125543 on energy balance and food deprivation-induced neuronal activation in obese Zucker rats
Authors: Doyon Christian , Samson Pierre , Lalonde Josée , Richard Denis
Published: March 2007

The corticotropin-releasing factor (CRF) system is involved in numerous physiological and behavioral actions, including the regulation of energy balance. We examined the effects of the CRF1 receptor antagonist, SSR125543, on energy balance and food deprivation-induced neuronal activation in obese rats. Lean (Fa/?) and obese (fa/fa) Zucker rats were treated orally with SSR125543 at a daily dose of 30 mg/kg for 21 days. Rats were killed either fed ad libitum or food deprived for 6 h in order to induce a mild stress response in obese rats. SSR125543 reduced plasma corticosterone levels in lean rats, prevented corticosterone response to fasting in obese rats, and increased CRF mRNA levels in the paraventricular hypothalamic nucleus (PVN) of both lean and obese rats, further confirming that the antagonist partially blocked CRF1 receptors. SSR125543 increased protein gain in obese rats. Whole carcass analyses showed reduced energy and fat gains in lean rats. Consistent with reduced fat gain, circulating triglyceride and leptin levels were reduced in SSR125543-treated lean rats. In obese rats, circulating glucose levels and the homeostasis model assessment of insulin resistance index of insulin resistance were reduced by SSR125543 treatment. CRF1 receptor blockade increased uncoupling protein-1 mRNA levels in interscapular brown adipose tissue of obese rats. The antagonist partly blocked the fasting-induced changes in c-fos mRNA levels in the PVN and arcuate nucleus of obese rats. Overall, these results suggest that although SSR125543 had relatively mild effects on energy balance, CRF1 receptor blockade attenuated several metabolic effects of short-term fasting and improved plasma variables related to the metabolic syndrome and diabetes.
Calpain inhibition impairs glycogen syntheses in HepG2 hepatoma cells without altering insulin signaling
Authors: Meier Markus , Klein Harald H , Kramer Jan , Drenckhan Maren , Schütt Morten
Published: March 2007

Calpains are a family of non-lysosomal cytoplasmatic cysteine proteases. Since calpain 10 (CAPN10), a member of the calpain family of proteases, has been found to represent a putative diabetes susceptibility gene, it was argued that calpains may be involved in the development of type 2 diabetes. The functional role of calpains in insulin signaling and/or insulin action is, however, not clear. We investigated the effects of the calpains 1 and 2 inhibitor PD151746 on insulin signaling and insulin action in human hepatoma G2 cells (HepG2). HepG2 cells were incubated without (−PD) or with (+PD) 5.33 μmol/l PD151746 for different times and then stimulated with 100 nmol/l insulin for 0 (t0), 5 (t5), 15 (t15), 30 (t30), 45 (t45), and 60 (t60) min. After solubilization of the cells, insulin receptor kinase activity, tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), IRS-1-associated phosphatidylinositol-3 kinase (PI3-kinase), PI3-kinase activity, Thr308 phosphorlyation of Akt, amount of protein tyrosine phosphatase-ε (PTPε), and glycogen synthase activity were determined. Incubation with PD151746 resulted in a significant reduction of insulin-stimulated glycogen synthesis compared with cells not pre-incubated with the calpain inhibitor (−PD: t0, 4.90 ± 1.20%; t5, 5.90 ± 1.02%; t15, 5.29 ± 0.95%; t30, 5.60 ± 1.10%; t45, 5.52 ± 0.90%; t60, 5.67 ± 0.97%;+PD: t0, 4.56 ± 1.10%; t5, 6.16 ± 1.05%; t15, 7.52 ± 1.09%; t30, 7.68 ± 1.10%; t45, 8.28 ± 0.89%; t60, 7.69 ± 0.98%; P < 0.05). Incubation with PD151746 significantly increased the protein amount of PTPε in the cells after 12 h (−PD: t1, 0.85 ± 0.18 RU (Relative unit); t8, 0.87 ± 0.18 RU; t12, 0.9 ± 0.13 RU; +PD: t1, 0.92 ± 0.21 RU; t8, 1.1 ± 0.15 RU; t12, 1.34 ± 0.16 RU; P < 0.05). Calpain inhibition with PD151746 had no effect on the insulin stimulation of the investigated insulin signaling parameters. These results in HepG2 cells suggest that calpains play a role in the hepatic regulation of insulin-stimulated glycogen synthesis independent of the PI3-kinase/Akt signaling pathway.
Gradients in bone morphogenetic protein-related gene expression across the growth plate
Authors: Nilsson Ola , Parker Elizabeth A , Hegde Anita , Chau Michael , Barnes Kevin M , Baron Jeffrey
Published: March 2007

In the growth plate, stem-like cells in the resting zone differentiate into rapidly dividing chondrocytes of the proliferative zone and then terminally differentiate into the non-dividing chondrocytes of the hypertrophic zone. To explore the molecular switches responsible for this two-step differentiation program, we developed a microdissection method to isolate RNA from the resting (RZ), proliferative (PZ), and hypertrophic zones (HZ) of 7-day-old male rats. Expression of approximately 29 000 genes was analyzed by microarray and selected genes verified by real-time PCR. The analysis identified genes whose expression changed dramatically during the differentiation program, including multiple genes functionally related to bone morphogenetic proteins (BMPs). BMP-2 and BMP-6 were upregulated in HZ compared with RZ and PZ (30-fold each, P < 0.01 and 0.001 respectively). In contrast, BMP signaling inhibitors were expressed early in the differentiation pathway; BMP-3 and gremlin were differentially expressed in RZ (100- and 80-fold, compared with PZ, P < 0.001 and 0.005 respectively) and growth differentiation factor (GDF)-10 in PZ (160-fold compared with HZ, P < 0.001). Our findings suggest a BMP signaling gradient across the growth plate, which is established by differential expression of multiple BMPs and BMP inhibitors in specific zones. Since BMPs can stimulate both proliferation and hypertrophic differentiation of growth plate chondrocytes, these findings suggest that low levels of BMP signaling in the resting zone may help maintain these cells in a quiescent state. In the lower RZ, greater BMP signaling may help induce differentiation to proliferative chondrocytes. Farther down the growth plate, even greater BMP signaling may help induce hypertrophic differentiation. Thus, BMP signaling gradients may be a key mechanism responsible for spatial regulation of chondrocyte proliferation and differentiation in growth plate cartilage.
Trends in Characteristics and Country of Origin Among Foreign-Trained Nurses in the United States, 1990 and 2000
Authors: Polsky Daniel , Ross Sara J. , Brush Barbara L. , Sochalski Julie
Published: March 2007

Objectives. We describe long-term trends in the characteristics of foreign-trained new entrants to the registered nurse (RN) workforce in the United States.

Methods. Using the 1990 and 2000 US Census 5% Public Use Microdata Sample files, we compared trends in characteristics of US- and foreign-trained new entrants to the RN labor force (n=40827) and identified trends in the country of origin of the foreign-trained new entrants.

Results. Foreign-trained RNs grew as a percentage of new entrants to the RN workforce, from 8.8% in 1990 to 15.2% in 2000. Compared with US-trained RNs, foreign-trained RNs were 3 times as likely to work in nursing homes and were more likely to have earned a bachelor’s degree. In 2000, 21% of foreign-trained RNs originated from low-income countries, a doubling of the rate since 1990.

Conclusions. Foreign-trained RNs now account for a substantial and growing proportion of the US RN workforce. Our findings suggest foreign-trained RNs entering the United States are not of lower quality than US-trained RNs. However, growth in the proportion of RNs from low-income countries may have negative consequences in those countries.
Effects of the Office of National Drug Control Policy’s Marijuana Initiative Campaign on High-Sensation-Seeking Adolescents
Authors: Palmgreen Philip , Lorch Elizabeth P. , Stephenson Michael T. , Hoyle Rick H. , Donohew Lewis
Published: March 2007

Objectives. We evaluated the effects of the Marijuana Initiative portion of the Office of National Drug Control Policy’s National Youth Anti-Drug Media Campaign on high-sensation-seeking and low-sensation-seeking adolescents.

Methods. Personal interviews were conducted via laptop computers with independent monthly random samples of 100 youths from the same age cohort in each of 2 moderate-sized communities over 48 months (April 1999–March 2003) of the campaign, including the critical first 6 months of the 9-month initiative. The start of the initiative was treated as an “interruption” in time-series analyses of the combined community sample.

Results. The Marijuana Initiative reversed upward developmental trends in 30-day marijuana use among high-sensation-seeking adolescents (P<.001) and significantly reduced positive marijuana attitudes and beliefs in this at-risk population. Use of control substances was not affected. As expected, low-sensation-seeking adolescents had low marijuana-use levels, and the campaign had no detectable effects on them. Other analyses indicated that the initiative’s dramatic depiction of negative consequences of marijuana use was principally responsible for its effects on high-sensation-seeking youths.

Conclusions. Substance use prevention campaigns can be effective within an approach using dramatic negative-consequence messages targeted to high-sensation seekers.