bluuebunny/crossref_metadata_2025 huggingface dataset:
A National Patient Navigator Training Program
Authors: Calhoun Elizabeth A. , Whitley Elizabeth M. , Esparza Angelina , Ness Elizabeth , Greene Amanda , Garcia Roland , Valverde Patricia A.
Published: December 2008

Patient Navigation is an intervention aimed at addressing cancer health disparities by eliminating barriers to diagnosis, treatment, and services. Three major patient navigation (PN) programs (The National Cancer Institute, The American Cancer Society &The Center for Medicare and Medicaid Services) are underway to address the needs of medically underserved cancer patients. There has not been national training with a defined curriculum for patient navigators (PNs). Curriculum for training the PNs was created by experts from the three programs. The efficacy of training was evaluated using a pre- and posttest. The data show that overall the posttest scores improved from the pretest. In addition, having a high school education or greater or having more years of work experience were significantly related to improvements on the posttest. The first successful standardized national training program was attended by 116 PNs representing 85 cities with the goal to reduce health disparities for medically underserved.
But Will I Be Re-Elected? What Happens to Local Level Policy Makers Who Support Clean Indoor Air Laws?
Authors: Eisenberg Merrill , McCotter Orion , Sciacca John
Published: December 2008

This research was conducted to determine the impact of voting for clean indoor air ordinance on a local-level policy maker’s re-election status. Secondary data were used to identify local tobacco ordinances in Arizona proposed between 2001 and 2005, score ordinance content for comprehensiveness, identify policy makers who voted and how they voted, and determine if the measure passed or failed. Participation in and outcomes of subsequent elections were documented from public records. Ninety-two local-level policy makers in 15 local jurisdictions considered clean indoor air laws between 2001 and 2005. Policy makers who voted for these ordinances were more likely to be re-elected than those who voted against them. Structured interviews revealed that policy makers did not believe the issue had an impact on re-election results and believed that although the issue may have been contentious, it was no longer salient in the community.
An Evaluation of the Experiences of Rural MSM Who Accessed an Online HIV/AIDS Health Promotion Intervention
Authors: Williams Mark , Bowen Anne , Ei Sue
Published: December 2008

The purpose of this study was to assess rural MSM’s satisfaction with an Internet-delivered HIV/AIDS intervention. Objectives were to evaluate if completion rates varied by characteristics, if completion varied by computer issues, if satisfaction changed from first to last modules, and if satisfaction was associated with module order. Data were collected from 300 rural MSM. Results showed few differences between men who completed the intervention and those who dropped out. Completion was associated with income, accessing the intervention at home, time to load screens, and finding navigation easy. For those completing the intervention, interest in and perceived usefulness of the information increased from first to the last module. Module order was associated with the knowledge module. Interest in the module was greatest if it was encountered last. Results indicate that rural MSM are willing to enroll in and complete an Internet-delivered HIV/AIDS risk reduction intervention.
Center for Disease Control’s Diethylstilbestrol Update: A Case for Effective Operationalization of Messaging in Social Marketing Practice
Authors: Mattson Marifran , Basu Ambar
Published: December 2008

The Center for Disease Control’s (CDC) Diethylstilbestrol (DES) Update, a campaign to educate people who may have been exposed to the drug DES, is framed on the premises of the social marketing model, namely formative research, audience segmentation, product, price, placement, promotion, and campaign evaluation. More than that, the campaign takes a critical step in extending the social marketing paradigm by highlighting the need to situate the messaging process at the heart of any health communication campaign. This article uses CDC’s DES Update as a case study to illustrate an application of a message development tool within social marketing. This tool promotes the operationalization of messaging within health campaigns. Ultimately, the goal of this project is to extend the social marketing model and provide useful theoretical guidance to health campaign practitioners on how to accomplish stellar communication within a social marketing campaign.
Promoting Community Preparedness: Lessons Learned From the Implementation of a Chemical Disaster Tabletop Exercise
Authors: High Erika H. , Lovelace Kay A. , Gansneder Bruce M. , Strack Robert W. , Callahan Barbara , Benson Phillip
Published: December 2008

Health educators are frequently called on to facilitate community preparedness planning. One planning tool is community-wide tabletop exercises. Tabletop exercises can improve the preparedness of public health system agencies to address disaster by bringing together individuals representing organizations with different roles and perspectives in specific disasters. Thus, they have the opportunity to identify each other’s roles, capabilities, and limitations and to problem-solve about how to address the gaps and overlaps in a low-threat collaborative setting. In 2005, the North Carolina Office of Public Health Preparedness and Response developed a series of exercises to test the preparedness for chemical disasters in a metropolitan region in the southeastern United States. A tabletop exercise allowed agency heads to meet in an environment promoting inter- and intraagency public—private coordination and cooperation. The evaluation results reported here suggest ways in which any tabletop exercise can be enhanced through recruitment, planning, and implementation.
Adaptation of a Lay Health Advisor Model as a Recruitment and Retention Strategy in a Clinical Trial of College Student Smokers
Authors: Varvel Shiloh Jordan , Cronk Nikole J. , Harris Kari Jo , Scott Anne B.
Published: December 2008

This study describes and provides results from a process evaluation of a lay health advisor (LHA) model to enhance participation in a clinical trial of the effectiveness of motivational interviewing on smoking cessation in college fraternity and sorority members. The implementation of the model had two phases: (a) the selection and training of LHAs as liaisons between research staff and participants and (b) LHAs’ roles in recruitment and retention. Perceptions of the LHA model were explored using survey questionnaires. Trial participants (N = 118) and LHAs (N = 8) were generally satisfied with the model and identified LHAs as helpful to participation. Seventy-four percent of chapter members were screened and 73% of participants received three of the four motivational interviewing sessions. These results indicate the LHA model was well received and met the needs of the research project.
Expanding Education Technology to Meet the Needs of Patients, Families, and Clinicians
Authors: DeMarco Jodi , Nystrom Meg Schuster
Published: December 2008

With the patient length of hospital stay continuously decreasing, health educators and nurses are continually challenged to adequately educate patients prior to discharge. Health education is recognized as a key component for reducing readmission rates by increasing patient compliance, yet health education resources must be readily accessible to patients throughout the entire hospital experience in order to achieve fulfillment. The Center for Consumer Health Information at Cleveland Clinic examined the existing in-hospital delivery systems in order to identify a means to reach patients at all access points in the health care process. This article demonstrates how a closed circuit television system may be utilized to deliver health education content to individuals in both in-patient and out-patient settings. The evaluation of vendors and identification of internal resources is imperative to the successful implementation of an in-patient education system.
Education as Catalyst for Intergenerational Refugee Family Communication About War and Trauma
Authors: Lin Nancy J. , Suyemoto Karen L. , Kiang Peter Nien-chu
Published: December 2008

This article describes influences on intergenerational communication within refugee families about sociocultural trauma and explores how education may positively affect this communication process. Drawing on qualitative research and grounded theory through a larger study concerning intergenerational effects of and communication about trauma in Cambodian American refugee families, this article highlights ways that education may contribute to healing broken narratives within refugee families affected by war and genocide. Although focusing on Cambodian American experiences, we suggest that the role of education may be similarly helpful in facilitating intergenerational communication for other individuals with personal and familial experiences with trauma, such as students from refugee families who have fled Vietnam, Somalia, Bosnia, and other sites of forced migration.
A Review of Telephone-Administered Screening Tests for Dementia Diagnosis
Authors: Smith Megan M. , Tremont Geoffrey , Ott Brian R.
Published: December 2008

Dementia screening measures serve an important role in epidemiological research, clinical trials, identifying patients for more comprehensive assessment, and monitoring progression. Telephone-administered measures allow increased flexibility. Although there are several extant telephone-administered measures that offer the promise of efficient detection of cognitive impairment, research evidence supporting their use is limited. We review telephone-based cognitive screening instruments for detecting dementia or mild cognitive impairment, critically review the evidence for their validity, and make recommendations for future research directions. Most measures reviewed do a good job of classifying patients as likely to have dementia or likely to be neurologically healthy. However, with sensitivity values ranging from 38% to 100% and specificity values ranging from 79% to 100%, there is considerable variability in the measures available. Future validation studies should reflect the populations most likely to benefit from a telephone-based measure, namely community-dwelling elderly who have not yet been identified as being cognitively impaired.
Neural Stem Cells and Alzheimer's Disease: Challenges and Hope
Authors: Zhongling Feng  , Gang Zhao  , Lei Yu
Published: December 2008

Alzheimer's disease is characterized by degeneration and dysfunction of synapses and neurons in brain regions critical for learning and memory functions. The endogenous generation of new neurons in certain regions of the mature brain, derived from primitive cells termed neural stem cells, has raised hope that neural stem cells may be recruited for structural brain repair. Stem cell therapy has been suggested as a possible strategy for replacing damaged circuitry and restoring learning and memory abilities in patients with Alzheimer's disease. In this review, we outline the promising investigations that are raising hope, and understanding the challenges behind translating underlying stem cell biology into novel clinical therapeutic potential in Alzheimer's disease.
Coping as a Mediator of the Effects of Stressors and Supports on Depression Among Girls in Juvenile Justice
Authors: Goodkind Sara , Ruffolo Mary C. , Bybee Deborah , Sarri Rosemary
Published: December 2008

Research from many disciplines, including sociology, psychology, criminology, and social work, has examined the effects of stressors or risk factors and supports or protective factors on negative outcomes such as mental health problems and delinquent behavior. Drawing on these multiple literatures, this study examines relationships among stressors (experiences of abuse and other negative life events), support provided by family and friends, and depressive symptoms, as mediated by negative coping behaviors, for girls involved or at risk of involvement with juvenile justice. Data were obtained from surveys of 186 girls in juvenile justice and alternative programs. Analyses using structural equation modeling revealed that girls' experiences of physical and emotional abuse and other negative life events, partially mediated by their use of withdrawal and acting out coping strategies, predicted high levels of depressive symptoms, whereas family support was associated with lower levels of depressive symptoms.
Technologies Between Games and Culture
Authors: Crogan Patrick , Kennedy Helen
Published: December 2008

This article introduces and situates the ensuing collection of four essays on the theme of games and technology. It argues the need for videogame studies to develop a more rigorous and focused perspective on the theorization of technology as it relates to research into games and culture. The ``and'' in games and culture cannot begin to be understood comprehensively without a thinking of the profound reliance of both terms on technology. Players and their cultural and collective involvements should be taken not as stable categories of research and development but as processes of becoming intertwined with lineages of technological development and disjunction which are the condition of these processes. Video games are not the least component and proponent of these technological lineages today. The essays collected in this section of the journal issue are described and characterized as offering such a focus on ludic technicity through their diverse but intersecting considerations of game hardware, software, game play, and other practices appropriating game technologies.
Controller, Hand, Screen
Authors: Kirkpatrick Graeme
Published: December 2008

This paper tries to clarify the place of the handheld controller in computer game aesthetics. It starts from the premise that aesthetic form, perhaps the central category of modernist critical theory, is present in our play with computer games. The central argument is that controllers and our use of them are repressed in gameplay and that this repression facilitates a diversion of the player's energy that helps explain the compulsive nature of good games. Our sense of participation in events in game fiction is bought at the price of a loss of interest in our hands. The smooth integration of players into the rough, faltering world of gameplay is made possible by an excess of energy that passes from the unacknowledged tension in the hand into the imaginary relation we have with on-screen action.
Physical Activity, Sedentary Behavior, and Overweight/Obesity in Youth: Evidence From Cross-sectional, Longitudinal, and Interventional Studies
Authors: Zoeller Robert F.
Published: December 2008

Many children and adolescents in the United States do not meet the minimum recommendations for physical activity. In addition, both cross-sectional and longitudinal studies suggest that American youth become even more inactive as they mature. Girls are less active than boys at all ages, and minority youth demonstrate higher prevalences of physical inactivity. A large proportion of young people engage in sedentary behaviors such as watching television for prolonged periods of time. Data from the National Health and Nutrition Examination Survey and the Centers for Disease Control and Prevention show that at least 1 in 4 youth watch television and/or play computer games >4 hours per day. The prevalence of overweight and obesity in children and adolescents has increased dramatically in recent decades. Most studies have found a negative relationship between the amount of physical activity, especially of vigorous intensity, and the prevalence of overweight/obesity. Time spent watching television and playing on the computer was also predictive of overweight/obesity. Some studies have shown that sedentary behaviors such as prolonged television viewing may predict weight status in youth independent of physical activity level. Many studies using physical activity as an intervention to prevent weight gain or induce weight loss in youth suffer from methodological limitations that make it difficult to draw conclusions about the efficacy of these interventions or the volume and/or intensity of activity required. Limited evidence suggests that a greater volume of activity (>150 minutes per week) has the potential to achieve greater results. Better designed studies are needed to answer these important questions.
Joining of Cf/SiC composite to Ti alloy using composite filler materials
Authors: Xiong J. , Huang J. , Wang Z. , Lin G. , Zhang H. , Zhao X.
Published: December 2008

Cf/SiC was successfully joined to Ti alloy with Ag–Cu–Ti–W, Ag–Cu–Ti–SiC and Ag–Cu–Ti–TiC mixed powders by some suitable brazing parameters. Microstructure and shear strengths of the preformed joint were investigated. The results showed that the W particulate and reaction products can uniformly distribute in the brazing layer of the performed joint. These composite brazing layers relaxed the thermal stress of the joint effectively. These characteristics were beneficial to the joint, which had shear strengths that were significantly higher than the optimal shear strengths of the joint brazed with pure Ag–Cu–Ti at room temperature and 500°C.
Long-term relapses after 12-month treatment forMycobacterium kansasiilung disease
Authors: Santin M. , Dorca J. , Alcaide F. , Gonzalez L. , Casas S. , Lopez M. , Guerra M. R.
Published: December 2008

Long-lasting therapy forMycobacterium kansasiilung disease with rifampin-containing multidrug regimens is needed to avoid relapses. The aim of the present study is to evaluate a short multidrug treatment regimen forM. kansasiilung disease.

A retrospective observational study of 75 patients withM. kansasiilung disease was conducted in a teaching hospital from January 1990 to December 2005.

In total, 75 (67.6%) out of 111 patients diagnosed withM. kansasiilung disease completed a 12-month multidrug treatment regimen, including rifampin, isoniazid and ethambutol, supplemented with streptomycin during the first 2–3 months. After a 41.5-month median follow-up, five (6.6%) patients relapsed. The relapse rate was 2.19 (95% confidence interval 0.71–5.12) per 100 person·yrs. Treatment compliance was considered to be appropriate in all five patients and no drug resistance developed in any case.

In conclusion, a 12-month fixed-course treatment is effective in most cases ofMycobacterium kansasiilung disease, but may not be long enough for all patients.
Integrated PET/CT in the staging of nonsmall cell lung cancer: technical aspects and clinical integration
Authors: De Wever W. , Stroobants S. , Coolen J. , Verschakelen J. A.
Published: December 2008

Lung cancer is a common disease and is a leading cause of death in many countries. The management of lung cancer is directed by an optimal staging of the tumour. Integrated positron emission tomography (PET)/computed tomography (CT) is an anatomo-metabolic imaging modality that has recently been introduced to clinical practice and combines two different techniques: CT, which provides very detailed anatomic information; and PET, which provides metabolic information. One of the advantages of PET/CT is the improved image interpretation. This improvement can result in the detection of lesions initially not seen on CT or PET, a more precise location of lesions, a better characterisation of the lesion as benign or malignant and a better differentiation between tumour and surrounding structures. Initial studies demonstrate better results for PET/CT in the staging of lung cancer in comparison with PET alone, CT alone or visual correlation of PET and CT. The purpose of the present article is to discuss technical aspects of integrated PET/CT and to attempt to outline how to introduce integrated PET/CT in clinical and daily practice.
Long-term macrolide therapy in chronic inflammatory airway diseases
Authors: Crosbie P. A. J. , Woodhead M. A.
Published: December 2008

In addition to direct antibacterial actions, 14- and 15-member-ring macrolides have immune modulating effects that appear to be the reason for clinical benefit in diffuse panbronchiolitis.

A literature search was conducted for studies of the clinical effectiveness of macrolides in other chronic lung conditions.

A number of studies were identified that showed short-term beneficial outcomes or the potential for such outcomes in cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, asthma and post-transplant obliterative bronchiolitis. The studies were limited by small patient numbers, different outcome measures and short-term follow-up, and were not designed to assess potentially harmful effects.

Further large prospective and long-term studies are required in order to identify potential benefit and harm before these agents can be recommended routinely for these conditions.
Animal models of ventilator-associated pneumonia
Authors: Luna C. M. , Sibila O. , Agusti C. , Torres A.
Published: December 2008

Animal models are an essential step between “in vitro” testing and clinical studies. Different animal models have been useful for the study of pathophysiology, diagnosis and therapy in ventilator-associated pneumonia (VAP).

Aspiration has been studied in dog and cat models and bacteriological diagnosis has been evaluated in baboons. Pigs have been used for studying either spontaneous or induced VAP. Intubated piglets in prone position were administered analgesia and muscle paralysis was induced, and the intubated piglets underwent mechanical ventilation for several days. In this model, spontaneous VAP due to common bacterial pig colonisation develops within a few days. Pneumonia can also be induced by inoculating high concentrations of microorganisms (Pseudomonas aeruginosaand methicillin-resistantStaphylococcus aureus).

Different clinical, physiological, microbiological and pathological parameters of infection have been studied in this model. In addition, administration of antibiotics and inflammatory modulators and their consequences in microbiological eradication and local and systemic inflammation have been evaluated with interesting translational results.

Although bronchial inoculation of healthy subjects does not resemble the common pathophysiological mechanisms, the experimental model of ventilator-associated pneumonia induced by the inoculation of high concentrations of microorganisms in mechanically ventilated piglets is useful for the study of the local and systemic responses of lung infection and for the determination of potential measures of prevention or therapeutic modulation.
Macrophages within NSCLC tumour islets are predominantly of a cytotoxic M1 phenotype associated with extended survival
Authors: Ohri C. M. , Shikotra A. , Green R. H. , Waller D. A. , Bradding P.
Published: December 2008

There is a marked survival advantage for patients with nonsmall cell lung cancer (NSCLC) expressing high numbers of macrophages in their tumour islets. The primary aim of the present study was to determine the immunological phenotype of NSCLC-associated macrophages.

CD68+macrophages expressing markers of a cytotoxic M1 phenotype or a noncytotoxic M2 phenotype were identified in the islets and stroma of surgically resected tumours from 20 patients with extended survival (median 92.7 months) and 20 with poor survival (median 7.7 months), using immunohistochemistry.

The islet density of both M1 and M2 macrophages was markedly increased in extended compared with poor survival patients. In the extended survival group, M1 islet density was significantly increased compared with M2 density, 70% of islet macrophages were positive for M1 markersversus38% for M2, and the islet:stromal ratio of M1 macrophages was markedly increased compared with M2. The 5-yr survival for patients with above and below median expression of M1 macrophages in the islets was >75 and <5%, respectively.

Macrophages infiltrating the tumour islets in nonsmall cell lung cancer were predominantly of the M1 phenotype in patients with extended survival. The survival advantage conferred by islet macrophage infiltration may be related to their cytotoxic antitumour activity.
Asthma therapy: how far have we come, why did we fail and where should we go next?
Authors: Janssen L. J.
Published: December 2008

Reversible airflow obstruction and nonspecific airway hyperresponsiveness are: 1) the two key features of asthma; 2) the primary concern for asthma patients; and 3) both directly caused by the airway smooth muscle (ASM). As such, controlling bronchoconstriction should be of primary importance. Unfortunately, all existing pharmacological asthma therapies that specifically target the ASM are based on decades old strategies.

In the present study, the evolution of pharmacological asthma therapy will be briefly discussed, some explanations will be suggested as to why substantial new advances in this area have not occurred in several years and, finally, several new directions for novel asthma therapies will be proposed.
Pulmonary veno-occlusive disease
Authors: Montani D. , Price L. C. , Dorfmuller P. , Achouh L. , Jaïs X. , Yaïci A. , Sitbon O. , Musset D. , Simonneau G. , Humbert M.
Published: December 2008

Pulmonary veno-occlusive disease (PVOD) is currently classified as a subgroup of pulmonary arterial hypertension (PAH) and accounts for 5–10% of cases initially considered to be idiopathic PAH. PVOD has been described as idiopathic or complicating other conditions, including connective tissue diseases, HIV infection, bone marrow transplantation, sarcoidosis and pulmonary Langerhans cell granulomatosis. PVOD shares broadly similar clinical presentation, genetic background and haemodynamic characteristics with PAH. Compared to PAH, PVOD is characterised by a higher male/female ratio, higher tobacco exposure, lower arterial oxygen tension at rest, lower diffusing capacity of the lung for carbon monoxide, and lower oxygen saturation nadir during the 6-min walk test. High-resolution computed tomography (HRCT) of the chest can be suggestive of PVOD in the presence of centrilobular ground-glass opacities, septal lines and lymph node enlargement. Similarly, occult alveolar haemorrhage is associated with PVOD. A noninvasive diagnostic approach using HRCT of the chest, arterial blood gases, pulmonary function tests and bronchoalveolar lavage could be helpful for the detection of PVOD patients and in avoiding high-risk surgical lung biopsy for histological confirmation. PVOD is characterised by a poor prognosis and the possibility of developing severe pulmonary oedema with specific PAH therapy. Lung transplantation is the treatment of choice. Cautious use of specific PAH therapy can, however, be helpful in some patients.
Pulmonary veno-occlusive disease in myeloproliferative disorder
Authors: Willems E. , Canivet J-L. , Ghaye B. , de Leval L. , Radermecker M. , Preiser J-C. , Beguin Y.
Published: December 2008

The present study reports a case of biopsy-proven pulmonary veno-occlusive disease as a cause of severe pulmonary hypertension in a patient suffering from a chronic myeloproliferative disorder. The pulmonary disease evolved favourably under treatment with defibrotide, a pro-fibrinolytic medication used in hepatic veno-occlusive disease.
Smoking characteristics of Polish immigrants in Dublin
Authors: Kabir Zubair , Clarke Vanessa , Keogan Sheila , Currie Laura M , Zatonski Witold , Clancy Luke
Published: December 2008

Background

This study examined two main hypotheses: a) Polish immigrants' smoking estimates are greater than their Irish counterparts (b) Polish immigrants purchasing cigarettes from Poland smoke "heavier" (≥ 20 cigarettes a day) when compared to those purchasing cigarettes from Ireland. The study also set out to identify significant predictors of 'current' smoking (some days and everyday) among the Polish immigrants.

Methods

Dublin residents of Polish origin (n = 1,545) completed a previously validated Polish questionnaire in response to an advertisement in a local Polish lifestyle magazine over 5 weekends (July–August, 2007). The Office of Tobacco Control telephone-based monthly survey data were analyzed for the Irish population in Dublin for the same period (n = 484).

Results

Age-sex adjusted smoking estimates were: 47.6% (95% Confidence Interval [CI]: 47.3%; 48.0%) among the Poles and 27.8% (95% CI: 27.2%; 28.4%) among the general Irish population (p < 0.001). Of the57% of smokers (n = 345/606) who purchased cigarettes solely from Poland and the 33% (n = 198/606) who purchased only from Ireland, 42.6% (n = 147/345) and 41.4% (n = 82/198) were "heavy" smokers, respectively (p = 0.79). Employment (Odds Ratio [OR]: 2.89; 95% CI: 1.25–6.69), lower education (OR: 3.76; 95%CI: 2.46–5.74), and a longer stay in Ireland (>24 months) were significant predictors of current smoking among the Poles. An objective validation of the self-reported smoking history of a randomly selected sub-sample immigrant group, using expired carbon monoxide (CO) measurements, showed a highly significant correlation coefficient (r = 0.64) of expired CO levels with the reported number of cigarettes consumed (p < 0.0001).

Conclusion

Polish immigrants' smoking estimates are higher than their Irish counterparts, and particularly if employed, with only primary-level education, and are overseas >2 years.
Gelatinase (MMP-2 and -9) expression profiles during gestation in the bovine endometrium
Authors: Kizaki Keiichiro , Ushizawa Koichi , Takahashi Toru , Yamada Osamu , Todoroki Junichi , Sato Takashi , Ito Akira , Hashizume Kazuyoshi
Published: December 2008

Background

Various molecules participate in implantation and maintaining endometrial function during gestation. The remodeling of endometrial matrices is a necessary process in the coordination of gestational progress. Matrix-metalloproteinases (MMPs) like gelatinases (MMP-2 and -9) and collagenase (MMP-1) are considered to play important roles in this process. We examined MMP-2 and -9 expression using zymography, in situ hybridization, real-time PCR, and microarray analysis to clarify their roles in the bovine endometrium during gestation.

Methods

Endometria, placentomes, and fetal membranes were collected from Japanese black cows that were killed on day 15 to 252 of gestation or during their estrous cycle. The gene expression of MMP-related molecules (mainly MMP-2 and -9) was examined using a custom-made microarray, real-time RT-PCR, and in-situ hybridization. Gelatinase activity was detected by zymography and film in situ zymography.

Results

Both gelatinases were expressed in the endometrium and fetal tissues throughout gestation. MMP-2 gene expression declined with the progress of gestation, but its intensity was maintained at a high level during the peri-implantation period and increased in late gestation. The expression level of MMP-9 was stably maintained, but was relatively low compared to that of MMP-2. These gene expression patterns matched those detected by zymography for the proteins. Microarray analysis suggested that the functions of MMP-2 during implantation and the last part of gestation are closely related with those of other molecules such as tissue inhibitors of metalloproteinase (TIMP)-2, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 1, membrane type 1 (MT1)-MMP, and extracellular matrix metalloproteinase inducer (EMMPRIN).

Conclusion

We detected MMP-2 and -9 gene expression in the bovine endometrium and placentome throughout gestation. These data suggest that MMP-2 is one of the main endometrial remodeling factors for implantation and pre-partum in cattle. In cows, as is the case in humans and rodents, gelatinases participate in endometrial remodeling, and their activities depend on the balance of activators and inhibitors; i.e., TIMP, MT-MMP, EMMPRIN, MMP-2, MMP-9, and so on.
Microsatellite instability at a tetranucleotide repeat in type I endometrial carcinoma
Authors: Choi Yoo Duk , Choi Jin , Kim Jo Heon , Lee Ji Shin , Lee Jae Hyuk , Choi Chan , Choi Ho Sun , Lee Min Cheol , Park Chang Soo , Juhng Sang Woo , Nam Jong Hee
Published: December 2008

Background

Microsatellite instability (MSI) at tri- or tetranucleotide repeat markers (elevated microsatellite alterations at selected tetranucleotide repeat, EMAST) has been recently described. But, the underlying genetic mechanism of EMAST is unclear. This study was to investigate the prevalence of EMAST, in type I endometrial carcinoma, and to determine the correlation between the MSI status and mismatch repair genes (MMR) or p53.

Methods

We examined the 3 mono-, 3 di-, and 6 tetranucleotide repeat markers by PCR in 39 cases of type I endometrial carcinoma and performed the immunohistochemistry of hMSH2, hMLH1, and p53 protein.

Results

More than two MSI at mono- and dinucleotide repeat markers was noted in 8 cases (MSI-H, 20.5%). MSI, at a tetranucleotide repeat, was detected in 15 cases (EMAST, 38.5%). In remaining 16 cases, any MSI was not observed. (MSS, 42.1%), MSI status was not associated with FIGO stage, grade or depth of invasion. The absence of expression of either one of both hMSH2 or hMLH1 was noted in seven (87.5%) of eight MSI-H tumors, one (6.3%) of 16 MSS tumors, and five (33.3%) of 15 EMAST tumors. (p = 0.010) The expression of p53 protein was found in one (12.5%) of eight MSI-H tumors, five (31.3%) of 16 MSS tumors, and seven of 15 EMAST tumors. (p = 0.247)

Conclusion

Our results showed that about 38.5% of type I endometrial carcinomas exhibited EMAST, and that EMAST was rarely associated with alteration of hMSH2 or hMLH1.
Repetition of acute poisoning in Oslo: 1-year prospective study
Authors: Heyerdahl Fridtjof , Bjornaas Mari Asphjell , Dahl Rune , Hovda Knut Erik , Nore Anne Kathrine , Ekeberg Oivind , Jacobsen Dag
Published: December 2008

Background

The repetition of acute poisoning occurs frequently. The intention may change between episodes and many poisonings are treated outside the hospital setting. Few studies have taken this into account.

Aims

To quantify the repetition frequency regardless of the level of health care or the intention behind the poisoning, and to identify possible risk factors for repetition.

Method

A prospective multicentre study of all acute poisonings in Oslo treated in hospital, at an out-patient clinic or by the ambulance service. Repetition was estimated using Kaplan– Meier calculations, and predictive factors were identified using Cox regression analysis.

Results

The estimated 1-year repetition rate was 30% (95% CI 24–35). Independent predictors of repetition were middle age (30–49 years), poisoning with opiates or sedatives, unemployment or living on social welfare, a previous suicide attempt, and a history of psychiatric treatment. Intention was not a significant predictor.

Conclusions

Repetition of acute poisoning is high, irrespective of the level of healthcare and the intention behind the poisoning.
Beyond the critical period: longitudinal study of 8-year outcome in first-episode non-affective psychosis
Authors: Crumlish Niall , Whitty Peter , Clarke Mary , Browne Stephen , Kamali Moayyad , Gervin Maurice , McTigue Orfhlaith , Kinsella Anthony , Waddington John L. , Larkin Conall , O'Callaghan Eadbhard
Published: December 2008

Background

The critical period hypothesis proposes that deterioration occurs aggressively during the early years of psychosis, with relative stability subsequently. Thus, interventions that shorten the duration of untreated psychosis (DUP) and arrest early deterioration may have long-term benefits.

Aims

To test the critical period hypothesis by determining whether outcome in non-affective psychosis stabilises beyond the critical period and whether DUP correlates with 8-year outcome; to determine whether duration of untreated illness (DUI) has any independent effect on outcome.

Method

We recruited 118 people consecutively referred with first-episode psychosis to a prospective, naturalistic cohort study.

Results

Negative and disorganised symptoms improved between 4 and 8 years. Duration of untreated psychosis predicted remission, positive symptoms and social functioning at 8 years. Continuing functional recovery between 4 and 8 years was predicted by DUI.

Conclusions

These results provide qualified support for the critical period hypothesis. The critical period could be extended to include the prodrome as well as early psychosis.
Diagnostic accuracy of 123I-FP-CIT SPECT in possible dementia with Lewy bodies
Authors: O'Brien John T. , McKeith Ian G. , Walker Zuzana , Tatsch Klaus , Booij Jan , Darcourt Jacques , Marquardt Moritz , Reininger Cornelia ,   for the DLB Study Group
Published: December 2008

Background

123I-FP-CIT SPECT (single photon emission computed tomography) can help in the differential diagnosis of probable dementia with Lewy bodies (Lewy body dementia) and Alzheimer's disease.

Aims

Our aim was to determine the accuracy of 123I-FP-CIT SPECT in diagnosing people with possible dementia with Lewy bodies.

Method

We undertook a 12-month follow-up of 325 individuals with probable or possible Lewy body or non-Lewy body dementia who had previously undergone 123I-FP-CIT SPECT. A consensus panel masked to SPECT findings, established diagnosis at 12 months in 264 people.

Results

Of 44 people with possible dementia with Lewy bodies at baseline, at follow-up the diagnosis for 19 people was probable dementia with Lewy bodies (43%), in 7 people non-Lewy body dementia (16%) and for 18 individuals it remained possible dementia with Lewy bodies (41%). Of the 19 who at follow-up were diagnosed with probable dementia with Lewy bodies, 12 had abnormal scans at baseline (sensitivity 63%); all 7 individuals with a possible diagnosis who were diagnosed as having Alzheimer's disease at follow-up had normal scans (specificity 100%).

Conclusions

Our findings confirm the diagnostic accuracy of 123I-FP-CIT SPECT in distinguishing Lewy body from non-Lewy body dementia and also suggest a clinically useful role in diagnostically uncertain cases, as an abnormal scan in a person with possible dementia with Lewy bodies is strongly suggestive of dementia with Lewy bodies.
Antidepressants on trial: how valid is the evidence?
Authors: Parker Gordon
Published: December 2008

A recent meta-analysis concluded that newer antidepressant drugs are equivalent to or no better than placebos, a conclusion at some variance with their commonly judged clinical effectiveness. The ‘disconnect’ between randomised controlled trials and clinical practice would benefit from dissection of contributing factors, and redressing limitations to current trial procedures.
Role of Type Iα Phosphatidylinositol-4-Phosphate 5-Kinase in Insulin Secretion, Glucose Metabolism, and Membrane Potential in INS-1 β-Cells
Authors: Zhang Jiping , Luo Ruihua , Wu Heqing , Wei Shunhui , Han Weiping , Li GuoDong
Published: December 2008

Insulin secretion from β-cells is regulated by a complex signaling network. Our earlier study has reported that Rac1 participates in glucose- and cAMP-induced insulin secretion probably via maintaining a functional actin structure for recruitment of insulin granules. Type Iα phosphatidylinositol-4-phosphate 5-kinase (PIP5K-Iα) is a downstream effector of Rac1 and a critical enzyme for synthesis of phosphatidylinositol-4,5-bisphosphate (PIP2). By using an RNA interference technique, PIP5K-Iα in INS-1 β-cells could be specifically knocked down by 70–75%. PIP5K-Iα knockdown disrupted filamentous actin structure and caused changes in cell morphology. In addition, PIP2 content in the plasma membrane was reduced and the glucose effect on PIP2 was abolished but without affecting glucose-induced formation of inositol 1,4,5-trisphosphate. At basal conditions (2.8 mm glucose), PIP5K-Iα knockdown doubled insulin secretion, elevated glucose metabolic rate, depolarized resting membrane potential, and raised cytoplasmic free Ca2+ levels ([Ca2+]i). The total insulin release at high glucose was increased upon PIP5K-Iα knockdown. However, the percent increment of insulin secretion by high glucose and forskolin over the basal release was significantly reduced, an effect more apparent on the late phase of insulin secretion. Metabolism and [Ca2+]i rises at high glucose were also attenuated in cells after PIP5K-Iα knockdown. In contrast, PIP5K-Iα knockdown had no effect on cell growth and viability. Taken together, our data suggest that PIP5K-Iα may play an important role in both the proximal and distal steps of signaling cascade for insulin secretion in β-cells.
Akt2 Regulation of Cdc2-Like Kinases (Clk/Sty), Serine/Arginine-Rich (SR) Protein Phosphorylation, and Insulin-Induced Alternative Splicing of PKCβII Messenger Ribonucleic Acid
Authors: Jiang Kun , Patel Niketa A. , Watson James E. , Apostolatos Hercules , Kleiman Eden , Hanson Olivia , Hagiwara Masatoshi , Cooper Denise R.
Published: December 2008

Serine/arginine-rich (SR) proteins play essential roles in the constitutive and regulated splicing of precursor mRNAs. Phosphorylation of the arginine/serine dipeptide-rich (RS) domain by SR protein kinases such as Cdc2-like kinases (Clk/Sty) modulates their subcellular localization and activation. However, it remains unclear how these kinases and their target SR proteins are regulated by extracellular signals. Regulation of protein kinase C βII (PKCβII) pre-mRNA alternative splicing via exon inclusion by Akt2, a central kinase in insulin action, involves phosphorylation of SR proteins. Here we showed that Akt2, in response to insulin, resulted in phosphorylation of Clk/Sty, which then altered SR protein phosphorylation in concert with Akt2. Insulin-stimulated PKCβII pre-mRNA splicing was blocked by Clk/Sty and phosphatidylinositol-3-kinase inhibitors, and diabetic Akt2-null mouse tissues had impaired phospho-Clk/Sty, SR protein phosphorylation, and PKCβII expression. Furthermore, we observed that Akt2 phosphorylated several SR proteins distinct from Clk/Sty in response to insulin. Akt2-catalyzed phosphorylation of Clk/Sty and SR proteins revealed a role for both kinases in splicing regulation indicating dual functions for Akt2 in response to insulin in this pathway.
Dorsal Hindbrain 5′-Adenosine Monophosphate-Activated Protein Kinase as an Intracellular Mediator of Energy Balance
Authors: Hayes Matthew R. , Skibicka Karolina P. , Bence Kendra K. , Grill Harvey J.
Published: December 2008

The fuel-sensing enzyme AMP-activated protein kinase (AMPK) has been implicated in central nervous system control of energy balance. Hypothalamic AMPK activity is increased by food deprivation, and this elevation is inhibited by refeeding or by leptin treatment. The contribution of extrahypothalamic AMPK activity in energy balance control has not been addressed. Here, we investigate the effects of physiological state on the AMPK activity in hindbrain nucleus tractus solitarius (NTS) neurons because treatments that reduce energy availability in these neurons trigger behavioral, endocrine, and autonomic responses to restore energy balance. Food-deprived rats showed significantly increased AMPK activity in both NTS- and hypothalamus-enriched lysates compared with those that were ad libitum fed. Pharmacological inhibition of AMPK activity in medial NTS neurons, by intraparenchymal injection of compound C, suppressed food intake and body weight gain compared with vehicle. Fourth ventricle (4th icv) compound C delivery increased heart rate and spontaneous activity in free-moving rats. Suppression of AMPK activity has been implicated in leptin’s anorectic action in the hypothalamus. Given the role of leptin signaling in food intake inhibition within the medial NTS, we also examined whether stimulation of hindbrain AMPK by 4th icv administration of 5-aminoimidazole-4-carboxamide-riboside (AICAR), an AMP-mimicking promoter of AMPK activity, could attenuate the inhibition of food intake by 4th icv leptin. The intake-suppressive effects of leptin (at 2 and 4 h) were completely reversed by AICAR. We conclude that 1) hindbrain AMPK activity contributes to energy balance control through regulation of food intake and energy expenditure, 2) leptin’s intake-reducing effects in the NTS are meditated by AMPK, and 3) central nervous system AMPK controls whole-body homeostasis at anatomically distributed sites across the neuraxis.
Study of Circulating Prohepcidin in Association with Insulin Sensitivity and Changing Iron Stores
Authors: Fernández-Real José Manuel , Equitani Francesco , Moreno José María , Manco Melania , Ortega Francisco , Ricart Wifredo
Published: December 2008

Background: Liver synthesizes hepcidin in response to iron overload, leading to down-regulation of duodenal iron absorption. The pathophysiology of type 2 diabetes is associated with increased iron stores. We aimed to study circulating prohepcidin in association with insulin sensitivity and parameters of glucose and iron metabolism.

Methods: Serum prohepcidin was evaluated in three cohorts: 1) a cross-sectional study (cohort 1, men from the general population; n = 135); 2) after decreasing iron stores in men with “high-ferritin” type 2 diabetes (cohort 2; n = 13); and 3) after decreasing iron stores in men carrying HFE gene mutations (cohort 3; n = 16). Insulin sensitivity was measured using either the minimal model or the clamp technique.

Results: Circulating prohepcidin correlated significantly with glycated hemoglobin (P < 0.0001), fasting glucose (P = 0.002), triglycerides (P = 0.007), high-density lipoprotein-cholesterol (P = 0.01), ferritin (P = 0.01), and soluble transferrin receptor concentration (P = 0.001) in subjects from cohort 1. Prohepcidin decreased significantly after iron depletion in patients with type 2 diabetes (P = 0.04) (cohort 2) and in carriers of HFE gene mutations (P = 0.03) (cohort 3). In the latter subjects, the change in serum prohepcidin after iron depletion was associated with the change in both fasting glucose transferrin (r = 0.58; P = 0.02) and saturation (r = 0.68; P = 0.005). The changes in insulin sensitivity were associated with those of liver iron content (r = −0.64; P = 0.007) and with those of serum prohepcidin (r = −0.50; P = 0.04) (cohort 3).

Conclusions: These associations suggest that circulating prohepcidin concentration is pathophysiologically associated with parameters of glucose and iron metabolism. A failure to increase prohepcidin synthesis is hypothesized to contribute to iron-induced disorders of glucose metabolism.