bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term oxygen therapy: review from the patients’ perspective
Authors: Cullen DL , Stiffler D
Published: July 2009

Chronic respiratory conditions are responsible for increasing numbers of patients in need of long-term oxygen therapy (LTOT). However, many patients do not use their oxygen as prescribed. Unless we can assist these patients in living with oxygen therapy, optimal clinical outcomes will not be achieved. We conducted a meta-synthesis of qualitative research studies. We included any qualitative study that focused on the psychosocial nature or experience of patients prescribed LTOT. Four research studies met the conditions of our search. We performed a rigorous methodological protocol for meta-synthesis as described by the Joanna Briggs Institute. A total of 12 findings formulated four themes. These themes included the following: adapting oxygen to life’s circumstances, living in a restricted world, self-management is fostered by oxygen, and submission and dependency. From the four thematic categories established, meta-synthesis resulted in two major results: persons prescribed oxygen rationalize its use while negotiating lifestyle interference and physical restrictions and the drive to care for one’s self is conflicted. This meta-synthesis showed that each oxygen user faces tremendous physical, psychological, and emotional challenges. They strive to adapt and maintain mastery but eventually oxygen dependency results. These challenges affect the patient’s ability to adhere to their treatment guidelines. These barriers and challenges are seldom addressed and are under-treated. Clinicians involved in LTOT need to be aware and work with the patients to facilitate their use of oxygen. Inclusion of the patients’ perspective can guide practice and assist with the development of new interventions and management strategies.
The prognostic value of C-reactive protein in long-term care patients requiring prolonged mechanical ventilation
Authors: Sierros V , Fleming R , Cascioli M , Brady T
Published: July 2009

C-reactive protein (CRP), a biomarker of inflammation, has predicted mortality in end-stage respiratory failure and in the critically ill patients. Our aim was to investigate if CRP can predict morbidity and mortality in patients requiring prolonged mechanical ventilation. A prospective study conducted in a ventilator weaning unit of a skilled nursing facility over 13 months included 98 patients older than 18 years of age requiring mechanical ventilation via tracheostomy. Serum CRP and albumin levels were tested on admission. Age, gender, body mass index (BMI), and diagnoses causing respiratory failure were recorded. The outcomes measured were as follows: hospitalization, weaned from mechanical ventilation, and death. Our population had a median age of 77 years and the median BMI, albumin, and mean CRP were 26 kg/m2, 2.25 g/dL, and 5.75 mg/dL, respectively. The most common diseases leading to respiratory failure were pulmonary, neurologic, and cardiac. The patients with the empiric cutoff CRP of <2 mg/dL ( n = 14) had 0% hospitalization rate at 2 weeks and 7% at 30 days, whereas the patients with CRP ≥ 2 mg/dL ( n = 84) had 26% hospitalization rate at 2 weeks and 38% at 30 days. Mortality for the patients with CRP ≥ 2 mg/dL was 26% at 60 days, whereas the CRP < 2 mg/dL patients had no mortality at 60 days ( P = 0.034). The patients who survived 60 days ( n = 70) had significantly lower median CRP levels than the nonsurvivors (4.1 mg/dL vs 8.5 mg/dL, P = 0.009). The area under the receiver operating characteristic (ROC) curve for CRP levels predicting 2-week hospitalization was not large at 0.617 and the optimum CRP cutoff point was >2.7 mg/dL. The sensitivity and negative predictive value of the 2-week hospitalization outcome were equally high at 96%. The area under the ROC curve for 60-day survival was 0.691, and its optimum CRP cutoff point was >3.7 mg/dL with 85% sensitivity and 91% negative predictive value. CRP was not able to predict weaning success in this setting where the 60-day weaning rate was 9%. A CRP level of ≤2.7 mg/dL may be used to screen for patients who are not likely to develop acute illness requiring early 2-week rehospitalization, and a CRP level of ≤3.7 mg/dL may be used to predict 60-day survival in patients with respiratory failure requiring prolonged mechanical ventilation in the long-term care setting.
Using Participatory Mapping to Inform a Community-Randomized Trial of HIV Counseling and Testing
Authors: Maman Suzanne , Lane Tim , Ntogwisangu Jacob , Modiba Precious , Vanrooyen Heidi , Timbe Andrew , Visrutaratna Surasing , Fritz Katherine
Published: July 2009

Participatory mapping and transect walks were used to inform the research and intervention design and to begin building community relations in preparation for Project Accept, a community-randomized trial sponsored by the National Institute of Mental Health. Project Accept is being conducted at five sites in four countries: Thailand, Zimbabwe, South Africa, and Tanzania. Results from the mapping exercises informed decisions such as defining community boundaries and identifying appropriate criteria for matching community pairs for the trial as well as where to situate the services. The mapping also informed intervention-related decisions such as where to situate the services. The participatory methods enabled researchers at each site to develop an understanding of the communities that could not have been derived from existing data or data collected through standard data collection techniques. Furthermore, the methods lay the foundation for collaborative community research partnerships.
Accountability in Training Transfer: Adapting Schlenker’s Model of Responsibility to a Persistent but Solvable Problem
Authors: Burke Lisa A. , Saks Alan M.
Published: July 2009

Decades have been spent studying training transfer in organizational environments in recognition of a transfer problem in organizations. Theoretical models of various antecedents, empirical studies of transfer interventions, and studies of best practices have all been advanced to address this continued problem. Yet a solution may not be so elusive. This paper spotlights the crucial role of accountability in solving the transfer problem by applying the theoretical lens of Schlenker ’s pyramid of accountability. A conceptual framework is advanced and implications for future research and practice are discussed. Recommendations for practice include conducting a training transfer accountability audit to determine where and for whom accountability lapses exist in an organization, developing and clearly communicating prescriptions and expectations for training transfer for each stakeholder group, and evaluating training transfer outcomes across training programs.
English-Language Learners: Implications of Limited Vocabulary for Cross-Language Transfer of Phonemic Awareness With Kindergartners
Authors: Atwill Kim , Blanchard Jay , Christie James , Gorin Joanna S. , García Hermán S.
Published: July 2009

Research examined the influence of native vocabulary development on cross-language transfer of phonemic awareness. Participants were Spanish-speaking kindergartners learning English in immersion classrooms. Results indicated that limited Spanish vocabulary development negatively influenced cross-language transfer of phonemic awareness to English. The results have clear and profound implications for Spanish-speaking children. Without foundational Spanish vocabulary skills needed to facilitate cross-language transfer of phonemic awareness to English, literacy acquisition difficulties will likely arise.
Effect of PJ34 on Spinal Cord Tissue Viability and Gene Expression in a Murine Model of Thoracic Aortic Reperfusion Injury
Authors: Stone David H. , Conrad Mark F. , Albadawi Hassan , Entabi Fateh , Stoner Michael C. , Cambria Richard P. , Watkins Michael T.
Published: July 2009

Introduction: These studies were designed to determine whether PJ34, a novel Poly-ADP Ribose Polymerase Inhibitor, modulates expression of markers of stress and inflammation in the spinal cord following ischemia/ reperfusion(TAR). Methods: 129S1/SvImj mice were subjected to thoracic aortic occlusion and 48 hours of reperfusion (n = 38). Experimental Groups included: Untreated Control (UC, n = 21); PJ34 (PJ34, n = 11) and sham (S, n = 6). At 48 hours, mice were euthanized for mRNA analysis and assessment of spinal cord viability. Results: PJ34 improved spinal cord tissue viability following TAR (UC:53.1 ± 6.3, PJ34:73.5 ± 4.1% sham, p < 0.01). mRNA analysis revealed significant expression of stress response genes in UC and PJ34 treated mice. Conclusions: PJ34 enhanced mitochondrial activity and preserved neurologic function following TAR despite the expression of stress and pro-inflammatory markers within the spinal cord. The ongoing cord stress response in neurologically intact PJ34 treated mice may indicate the potential to develop delayed neurologic dysfunction.
Great Saphenous Vein Harvesting: A Systematic Review and Meta-Analysis of Open Versus Endoscopic Techniques
Authors: Cadwallader Rosemary Anne , Walsh Stewart R. , Cooper David G. , Tang Tjun Y. , Sadat Umar , Boyle Jonathan R.
Published: July 2009

Background: The great saphenous vein is frequently harvested for use as a conduit in lower limb bypass surgery. A number of papers advocate the use of an endoscopic technique rather than a traditional open technique to minimize the associated morbidity. We undertook a systematic review and meta-analysis to compare morbidity associated with these 2 techniques. Method: Medline, PubMed, and secondary referencing identified 16 randomized control trials comparing these 2 methods of harvesting. Primary outcome measures were infection, hematoma, and wound dehiscence and pooled odds ratios (POR) were calculated using a random effects model. Results: Sixteen trials (3689 patients) were identified. Overall complications (POR 7.03), infection (POR 8.08), and wound dehiscence (POR 8.23) were all significantly more common in the open harvesting group compared to the endoscopic group. Conclusion: Endoscopic techniques have a role in vein harvesting but are operator dependent and therefore are only a preferable modality compared to open harvesting methods in experienced hands. More research is required to establish whether long-term patency rates are comparable for the 2 techniques.
Intravascular Ultrasound—Guided Inferior Vena Cava Filter Placement in the Military Multitrauma Patients: A Single-Center Experience
Authors: Aidinian Gilbert , Fox Charles J. , White Paul W. , Cox Mitchell W. , Adams Eric D. , Gillespie David L.
Published: July 2009

Background: High velocity fragments have resulted in a multitude of complex injuries in the military patients, placing them at increased risk of venous thromboembolism. Methods: A retrospective analysis was performed of all the intravascular ultrasound (IVUS)-guided bedside inferior vena cava (IVC) filters placed between August 2003 and October 2007. Results: Fourteen patients had bedside IVUS-guided retrievable filter placement. Thirteen males and one female and the mean (+SD) injury severity scores (ISS) was 37.2 (+9.9). The most common causes of injury were explosive devices (57%), gunshot wounds (28%), rocket-propelled grenades (7%), and motor vehicle crashes (7%). Indications for filter insertion were deep venous thrombosis in 36% of patients and pulmonary embolus in 28%. Thirty five percent had filters inserted prophylactically. Conclusions: Military trauma population ISS is considerably higher than what is reported in the civilian population. The bedside IVUS-guided IVC filter insertion is particularly useful in this population.
Is Atherectomy the Best First-Line Therapy for Limb Salvage in Patients With Critical Limb Ischemia?
Authors: Loor Gabriel , Skelly Christopher L. , Wahlgren Carl-Magnus , Bassiouny Hisham S. , Piano Giancarlo , Shaalan Wael , Desai Tina R.
Published: July 2009

Objective: To determine the efficacy of atherectomy for limb salvage compared with open bypass in patients with critical limb ischemia. Methods: Ninety-nine consecutive bypass and atherectomy procedures performed for critical limb ischemia between January 2003 and October 2006 were reviewed. Results: A total of 99 cases involving TASC C (n = 43, 44%) and D (n = 56, 56%) lesions were treated with surgical bypass in 59 patients and atherectomy in 33 patients. Bypass and atherectomy achieved similar 1-year primary patency (64% vs 63%; P = .2). However, the 1-year limb salvage rate was greater in the bypass group (87% vs 69%; P = .004). In the tissue loss subgroup, there was a greater limb salvage rate for bypass patients versus atherectomy (79% vs 60%; P = .04). Conclusions: Patients with critical limb ischemia may do better with open bypass compared with atherectomy as first-line therapy for limb salvage.
Evaluation of Serum Matrix Metalloproteinases as Biomarkers for Detection of Neurological Symptoms in Carotid Artery Disease
Authors: Heider Peter , Pelisek Jaroslav , Poppert Holger , Eckstein Hans-Henning
Published: July 2009

Objective: Relevant soluble matrix metalloproteinases (MMPs), their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), and serological factors were analyzed as possible biomarkers for neurological symptoms in patients with carotid artery stenosis. Methods and Results: Asymptomatic (n = 76) and symptomatic (n = 69) patients were evaluated. Serum levels of collagenases (MMP-1, -8), gelatinases (MMP-2, -9), stromelysin (MMP-3), matrilysin (MMP-7), and TIMP-1, -2 were determined by enzyme-linked immunosorbant assay (ELISA). Furthermore, fibrinogen, C-reactive protein (CRP), leukocytes, and further serological parameters were measured. Circulating MMP-7, -8, -9, and TIMP-1 were significantly enhanced in symptomatic individuals with P < .001 for MMP-7 and P < .05 for MMP-8, -9, and TIMP-1. Significant correlations were found between various MMPs with highest correlation coefficient of r = .749 between MMP-8 and -9. In addition, MMP-1, -3, -7, -9 correlated significantly with leukocytes, MMP-1, and TIMP-1 with thrombocytes, MMP-8 with fibrinogen, and MMP-7 with creatinine. Combination of more than one bio-marker led to significantly enhanced positive predictive value (PPV) for neurological symptom compared to single MMP (MMP-7 + MMP-9: PPV = 73.1%, MMP-7 + MMP-8 + MMP-9: PPV = 73.8% vs. PPV = 62.5%; P < .001). Conclusions: Thus, using appropriate analytical approaches, we showed for the first time the possibility to use set of relevant biomarkers as predictors of neurological symptoms. Such biomarkers together with current diagnostic techniques may further contribute to recognize vulnerable lesions to define patients at risk.
Epigenetic mechanisms of regulation of Foxp3 expression
Authors: Lal Girdhari , Bromberg Jonathan S.
Published: July 2009

Regulatory T cells play important roles in the control of autoimmunity and maintenance of transplantation tolerance. Foxp3, a member of the forkhead/winged-helix family of transcription factors, acts as the master regulator for regulatory T-cell (Treg) development and function. Mutation of the Foxp3 gene causes the scurfy phenotype in mouse and IPEX syndrome (immune dysfunction, polyendocrinopathy, enteropathy, X-linked syndrome) in humans. Epigenetics is defined by regulation of gene expression without altering nucleotide sequence in the genome. Several epigenetic markers, such as histone acetylation and methylation, and cytosine residue methylation in CpG dinucleotides, have been reported at the Foxp3 locus. In particular, CpG dinucleotides at the Foxp3 locus are methylated in naive CD4+CD25− T cells, activated CD4+ T cells, and TGF-β–induced adaptive Tregs, whereas they are completely demethylated in natural Tregs. The DNA methyltransferases DNMT1 and DNMT3b are associated with the Foxp3 locus in CD4+ T cells. Methylation of CpG residues represses Foxp3 expression, whereas complete demethylation is required for stable Foxp3 expression. In this review, we discuss how different cis-regulatory elements at the Foxp3 locus are subjected to epigenetic modification in different subsets of CD4+ T cells and regulate Foxp3 expression, and how these mechanisms can be exploited to generate efficiently large numbers of suppressive Tregs for therapeutic purposes.
CLEC-2 is an essential platelet-activating receptor in hemostasis and thrombosis
Authors: May Frauke , Hagedorn Ina , Pleines Irina , Bender Markus , Vögtle Timo , Eble Johannes , Elvers Margitta , Nieswandt Bernhard
Published: July 2009

Damage to the integrity of the vessel wall leads to exposure of the subendothelial extracellular matrix (ECM), triggering platelet activation and aggregation. This process is essential for primary hemostasis but it may also lead to arterial thrombosis. Although the mechanisms underlying platelet activation on the ECM are well explored, it is less clear which receptors mediate cellular activation in a growing thrombus. Here we studied the role of the recently identified C-type lectin-like receptor 2 (CLEC-2) in this process. We show that anti–CLEC-2 antibody treatment of mice leads to complete and highly specific loss of CLEC-2 in circulating platelets for several days. CLEC-2–deficient platelets displayed normal adhesion under flow, but subsequent aggregate formation was severely defective in vitro and in vivo. As a consequence, CLEC-2 deficiency was associated with increased bleeding times and profound protection from occlusive arterial thrombus formation. These results reveal an essential function of CLEC-2 in hemostasis and thrombosis.
Therapeutic effect of CD137 immunomodulation in lymphoma and its enhancement by Treg depletion
Authors: Houot Roch , Goldstein Matthew J. , Kohrt Holbrook E. , Myklebust June H. , Alizadeh Ash A. , Lin Jack T. , Irish Jonathan M. , Torchia James A. , Kolstad Arne , Chen Lieping , Levy Ronald
Published: July 2009

Despite the success of passive immunotherapy with monoclonal antibodies (mAbs), many lymphoma patients eventually relapse. Induction of an adaptive immune response may elicit active and long-lasting antitumor immunity, thereby preventing or delaying recurrence. Immunomodulating mAbs directed against immune cell targets can be used to enhance the immune response to achieve efficient antitumor immunity. Anti-CD137 agonistic mAb has demonstrated antitumor efficacy in various tumor models and has now entered clinical trials for the treatment of solid tumors. Here, we investigate the therapeutic potential of anti-CD137 mAb in lymphoma. We found that human primary lymphoma tumors are infiltrated with CD137+ T cells. We therefore hypothesized that lymphoma would be susceptible to treatment with anti-CD137 agonistic mAb. Using a mouse model, we demonstrate that anti-CD137 therapy has potent antilymphoma activity in vivo. The antitumor effect of anti-CD137 therapy was mediated by both natural killer (NK) and CD8 T cells and induced long-lasting immunity. Moreover, the antitumor activity of anti-CD137 mAb could be further enhanced by depletion of regulatory T cell (Tregs). These results support the evaluation of anti-CD137 therapy in clinical trials for patients with lymphoma.
Detailed analysis of p53 pathway defects in fludarabine-refractory chronic lymphocytic leukemia (CLL): dissecting the contribution of 17p deletion, TP53 mutation, p53-p21 dysfunction, and miR34a in a prospective clinical trial
Authors: Zenz Thorsten , Häbe Sonja , Denzel Tina , Mohr Julia , Winkler Dirk , Bühler Andreas , Sarno Antonio , Groner Silja , Mertens Daniel , Busch Raymonde , Hallek Michael , Döhner Hartmut , Stilgenbauer Stephan
Published: July 2009

The prognosis of fludarabine (F)–refractory chronic lymphocytic leukemia (CLL) is very poor, and underlying mechanisms are only partly understood. To assess the contribution of p53 abnormalities to F-refractory CLL, we studied TP53 mutations in the CLL2H trial (subcutaneous alemtuzumab; n = 99). We found TP53 mutations in 37% of patients. Twelve of 67 (18%) patients without the 17p deletion showed a TP53 mutation and 50% showed evidence of uniparental disomy. A total of 75% of cases with TP53 mutation (without 17p−) showed clonal evolution/expansion. TP53 mutations had no impact on overall survival (P = .48). CLL with the 17p deletion or TP53 mutation showed very low miR-34a expression. To investigate the mechanisms underlying refractory CLL beyond p53, we studied cases without 17p−/TP53 mutation in detail. In several paired samples before and after F-refractory disease, no change in p21/p53 induction was observed after DNA damage. Although TP53 mutations and 17p deletions are found in a high proportion of F-refractory CLL, more than half of the cases cannot be explained by p53 defects (deletion or mutation), and alternative mechanisms need to be investigated. Alemtuzumab is effective irrespective of genetic high-risk subgroups with TP53 mutations. These clinical trials are registered at www.clinicaltrials.gov as #NCT00274976.
Avoiding “sticker” shock
Authors: Green David
Published: July 2009

In this issue of Blood, Witt and colleagues show that it is safe to alter the frequency of laboratory monitoring from every 4 weeks to every 8 weeks in stable patients on long-term anticoagulant therapy.1
Transcranial Doppler ultrasonography predicts cardiovascular events after TIA
Authors: Holzer Katrin , Sadikovic Suwad , Esposito Lorena , Bockelbrink Angelina , Sander Dirk , Hemmer Bernhard , Poppert Holger
Published: July 2009

Background

Transient ischemic attack (TIA) patients are at high vascular risk. We assessed the value of extracranial (ECD) and transcranial (TCD) Doppler and duplex ultrasonography to predict clinical outcome after TIA.

Methods

176 consecutive TIA patients admitted to the Stroke Unit were recruited in the study. All patients received diffusion-weighted imaging, standardized ECD and TCD. At a median follow-up of 27 months, new vascular events were recorded.

Results

22 (13.8%) patients experienced an ischemic stroke or TIA, 5 (3.1%) a myocardial infarction or acute coronary syndrome, and 5 (3.1%) underwent arterial revascularization. ECD revealed extracranial ≥ 50% stenosis or occlusions in 34 (19.3%) patients, TCD showed intracranial stenosis in 15 (9.2%) and collateral flow patterns due to extracranial stenosis in 5 (3.1%) cases. Multivariate analysis identified these abnormal ECD and TCD findings as predictors of new cerebral ischemic events (ECD: hazard ratio (HR) 4.30, 95% confidence interval (CI) 1.75 to 10.57, P = 0.01; TCD: HR 4.73, 95% CI 1.86 to 12.04, P = 0.01). Abnormal TCD findings were also predictive of cardiovascular ischemic events (HR 18.51, 95% CI 3.49 to 98.24, P = 0.001).

Conclusion

TIA patients with abnormal TCD findings are at high risk to develop further cerebral and cardiovascular ischemic events.
Assessment of the effect of betaine on p16 and c-mycDNA methylation and mRNA expression in a chemical induced rat liver cancer model
Authors: Du Yan-ping , Peng Jun-sheng , Sun Ai , Tang Zhi-hong , Ling Wen-hua , Zhu Hui-lian
Published: July 2009

Background

The development and progression of liver cancer may involve abnormal changes in DNA methylation, which lead to the activation of certain proto-oncogenes, such as c-myc, as well as the inactivation of certain tumor suppressors, such as p16. Betaine, as an active methyl-donor, maintains normal DNA methylation patterns. However, there are few investigations on the protective effect of betaine in hepatocarcinogenesis.

Methods

Four groups of rats were given diethylinitrosamine (DEN) and fed with AIN-93G diets supplemented with 0, 10, 20 or 40 g betaine/kg (model, 1%, 2%, and 4% betaine, respectively), while the control group, received no DEN, fed with AIN-93G diet. Eight or 15 weeks later, the expression of p16 and c-myc mRNA was examined by Real-time PCR (Q-PCR). The DNA methylation status within the p16 and c-myc promoter was analyzed using methylation-specific PCR.

Results

Compared with the model group, numbers and areas of glutathione S-transferase placental form (GST-p)-positive foci were decreased in the livers of the rats treated with betaine (P < 0.05). Although the frequency of p16 promoter methylation in livers of the four DEN-fed groups appeared to increase, there is no difference among these groups after 8 or 15 weeks (P > 0.05). Betaine supplementation attenuated the down-regulation of p16 and inhibited the up-regulation of c-myc induced by DEN in a dose-dependent manner (P < 0.01). Meanwhile, increases in levels of malondialdehyde (MDA) and glutathione S-transferase (GST) in model, 2% and 4% betaine groups were observed (P < 0.05). Finally, enhanced antioxidative capacity (T-AOC) was observed in both the 2% and 4% betaine groups.

Conclusion

Our data suggest that betaine attenuates DEN-induced damage in rat liver and reverses DEN-induced changes in mRNA levels.
Adolescents' experience of comments about their weight – prevalence, accuracy and effects on weight misperception
Authors: Lo Wing-Sze , Ho Sai-Yin , Mak Kwok-Kei , Lai Yuen-Kwan , Lam Tai-Hing
Published: July 2009

Background

Weight comments are commonly received by adolescents, but the accuracy of the comments and their effects on weight misperception are unclear. We assessed the prevalence and accuracy of weight comments received by Chinese adolescents from different sources and their relation to weight misperception.

Methods

In the Hong Kong Student Obesity Surveillance (HKSOS) project 2006–07, 22612 students aged 11–18 (41.5% boys) completed a questionnaire on obesity. Students responded if family members, peers and professionals had seriously commented over the past 30 days that they were "too fat" or "too thin" in two separate questions. The accuracy of the comments was judged against the actual weight status derived from self-reported height and weight. Self-perceived weight status was also reported and any discordance with the actual weight status denoted weight misperception. Logistic regression yielded adjusted odd ratios for weight misperception by the type of weight comments received.

Results

One in three students received weight comments, and the mother was the most common source of weight comments. Health professional was the most accurate source of weight comments, yet less than half the comments were correct. Adolescents receiving incorrect comments had increased risk of having weight misperception in all weight status groups. Receiving conflicting comments was positively associated with weight misperception among normal weight adolescents. In contrast, underweight and overweight/obese adolescents receiving correct weight comments were less likely to have weight misperception.

Conclusion

Weight comments, mostly incorrect, were commonly received by Chinese adolescents in Hong Kong, and such incorrect comments were associated with weight misperception.
Different modulation by dietary restriction of adipokine expression in white adipose tissue sites in the rat
Authors: Romero María del Mar , Fernández-López José Antonio , Esteve Montserrat , Alemany Marià
Published: July 2009

Background

White adipose tissue (WAT) is a disperse organ acting as energy storage depot and endocrine/paracrine controlling factor in the management of energy availability and inflammation. WAT sites response under energy-related stress is not uniform. In the present study we have analyzed how different WAT sites respond to limited food restriction as a way to better understand the role of WAT in the pathogenesis of the metabolic syndrome.

Methods

Overweight male rats had their food intake reduced a 40% compared with free-feeding controls. On day ten, the rats were killed; circulating glucose, insulin, leptin, adiponectin, triacylglycerols and other parameters were measured. The main WAT sites were dissected: mesenteric, retroperitoneal, epididymal and subcutaneous inguinal, which were weighed and frozen. Later all subcutaneous WAT was also dissected and weighed. Samples were used for DNA (cellularity) analysis and mRNA extraction and semiquantitarive RT-PCR analysis of specific cytokine gene expressions.

Results

There was a good correlation between serum leptin and cumulative WAT leptin gene mRNA, but not for adiponectin. Food restriction reduced WAT size, but not its DNA content (except for epididymal WAT). Most cytokines were correlated to WAT site weight, but not to DNA. There was WAT site specialization in the differential expression (and probably secretion) of adipokines: subcutaneous WAT showed the highest concentration for leptin, CD68 and MCP-1, mesenteric WAT for TNFα (and both tissues for the interleukins 1β and 6); resistin was highly expressed in subcutaneous and retroperitoneal WAT.

Conclusion

Food restriction induced different patterns for mesenteric and the other WAT sites, which may be directly related to both the response to intestine-derived energy availability, and an inflammatory-related response. However, retroperitoneal WAT, and to a lower extent, subcutaneous and epididymal, reacted decreasing the expression of inflammatory markers and the signaling of decreased energy availability in their stores. The varying cytokine expression patterns highlight the fact that WAT sites show different inflammatory and signaling responses to energy availability; they are too much different to simply extend to the whole-body WAT the findings of one or even a couple of sites.
The mRNA expression of SATB1 and SATB2 in human breast cancer
Authors: Patani Neill , Jiang Wen , Mansel Robert , Newbold Robert , Mokbel Kefah
Published: July 2009

Background

SATB1 is a nuclear protein that has been recently reported to be a 'genome organizer' which delineates specific epigenetic modifications at target gene loci, directly up-regulating metastasis-associated genes while down-regulating tumor-suppressor genes. In this study, the level of mRNA expression of SATB1 and SATB2 were assessed in normal and malignant breast tissue in a cohort of women with breast cancer and correlated to conventional clinico-pathological parameters.

Materials and methods

Breast cancer tissues (n = 115) and normal background tissues (n = 31) were collected immediately after excision during surgery. Following RNA extraction, reverse transcription was carried out and transcript levels were determined using real-time quantitative PCR and normalized against β-actin expression. Transcript levels within the breast cancer specimens were compared to the normal background tissues and analyzed against TNM stage, nodal involvement, tumour grade and clinical outcome over a 10 year follow-up period.

Results

The levels of SATB1 were higher in malignant compared with normal breast tissue (p = 0.0167). SATB1 expression increased with increasing TNM stage (TNM1 vs. TNM2 p = 0.0264), increasing tumour grade (grade1 vs. grade 3 p = 0.017; grade 2 vs. grade 3 p = 0.0437; grade 1 vs. grade 2&3 p = 0.021) and Nottingham Prognostic Index (NPI) (NPI-1 vs. NPI-3 p = 0.0614; NPI-2 vs. NPI-3 p = 0.0495). Transcript levels were associated with oestrogen receptor (ER) positivity (ER(-) vs. ER(+) p = 0.046). SABT1 expression was also significantly correlated with downstream regulated genes IL-4 and MAF-1 (Pearson's correlation coefficient r = 0.21 and r = 0.162) and SATB2 (r = 0.506). After a median follow up of 10 years, there was a trend for higher SATB1 expression to be associated with shorter overall survival (OS). Higher levels of SATB2 were also found in malignant compared to background tissue (p = 0.049). SATB2 expression increased with increasing tumour grade (grade 1 vs. grade 3 p = 0.035). SATB2 was associated with ER positivity (ER(-) vs. ER(+) p = 0.0283) within ductal carcinomas. Higher transcript levels showed a significant association with poorer OS (p = 0.0433).

Conclusion

SATB1 mRNA expression is significantly associated with poor prognostic parameters in breast cancer, including increasing tumour grade, TNM stage and NPI. SATB2 mRNA expression is significantly associated with increasing tumour grade and poorer OS. These results are consistent with the notion that SATB1 acts as a 'master genome organizer' in human breast carcinogenesis.
14-3-3σ gene silencing during melanoma progression and its role in cell cycle control and cellular senescence
Authors: Schultz Julia , Ibrahim Saleh M , Vera Julio , Kunz Manfred
Published: July 2009

Background

The family of 14-3-3 proteins plays an important role in cancer biology by interfering with intracellular signalling pathways and cell cycle checkpoints. The 14-3-3σ isoform acts as a tumor suppressor and is often inactivated during tumor development.

Results

Here, we demonstrate enhanced CpG methylation of the 14-3-3σ gene in lymph node and cutaneous melanoma metastases compared with primary tumors, associated with dramatically reduced mRNA expression. In line with this, treatment of different metastatic melanoma cell lines with 5-aza-2'-deoxycytidine (5-Aza-CdR), a potent inhibitor of cytosine methylation, significantly induces 14-3-3σ protein expression. Additional treatment with histone deacetylase inhibitor 4-phenylbutyric acid (Pba) further enhances 14-3-3σ expression. Induction of 14-3-3σ expression by 5-Aza-CdR/Pba treatment leads to almost complete inhibition of cell proliferation, with cells predominantly arrested in G2-M. The antiproliferative effect of 5-Aza-CdR/Pba was reversed in 14-3-3σ knockdown cells. Similarly, melanoma cell lines stably overexpressing 14-3-3σ show dramatically reduced cell proliferation rates. Moreover, synchronous 14-3-3σ stably overexpressing cells do not progress through cell cycle, but display a permanent increase in the population of 4n DNA containing cells. Interestingly, overexpression of 14-3-3σ induces senescence of melanoma cells and is involved in melanoma cell senescence under genotoxic stress. Finally, 14-3-3σ knockdown supports migratory capacity of melanoma cells in vitro, while 14-3-3σ overexpression has opposing effects.

Conclusion

Taken together, the present report indicates that epigenetic silencing of 14-3-3σ might contribute to tumor progression in malignant melanoma via loss of cell cycle control, impaired cellular senescence program and support of migratory capacity.
Dental pain, oral impacts and perceived need for dental treatment in Tanzanian school students: a cross-sectional study
Authors: Mashoto Kijakazi O , Åstrøm Anne N , David Jamil , Masalu Joyce R
Published: July 2009

Background

Dental caries, dental pain and reported oral problems influence people's oral quality of life and thus their perceived need for dental care. So far there is scant information as to the psychosocial impacts of dental diseases and the perceived treatment need in child populations of sub-Saharan Africa.

Objectives

Focusing on primary school students in Kilwa, Tanzania, a district deprived of dental services and with low fluoride concentration in drinking water, this study aimed to assess the prevalence of dental pain and oral impacts on daily performances (OIDP), and to describe the distribution of OIDP by socio-demographics, dental caries, dental pain and reported oral problems. The relationship of perceived need estimates with OIDP was also investigated.

Methods

A cross-sectional study was conducted in 2008. A total of 1745 students (mean age 13.8 yr, sd = 1.67) completed an extensive personal interview and under-went clinical examination. The impacts on daily performances were assessed using a Kiswahili version of the Child-OIDP instrument and caries experience was recorded using WHO (1997) criteria.

Results

A total of 36.2% (41.3% urban and 31.4% rural, p < 0.001) reported at least one OIDP. The prevalence of dental caries was 17.4%, dental pain 36.4%, oral problems 54.1% and perceived need for dental treatment 46.8% in urban students. Corresponding estimates in rural students were 20.8%, 24.4%, 43.3% and 43.8%. Adjusted OR for reporting oral impacts if having dental pain ranged from 2.5 (95% CI 1.8–3.6) (problem smiling) to 4.7 (95% CI 3.4–6.5) (problem sleeping),- if having oral problems, from 1.9 (95% CI 1.3–2.6) (problem sleeping) to 3.8 (95% CI 2.7–5.2) (problem eating) and if having dental caries from 1.5 (95% CI 1.1–2.0) (problem eating) to 2.2 (95% CI 1.5–2.9) (problem sleeping). Students who perceived need for dental care were less likely to be females (OR = 0.8, 95% CI 0.6–0.9) and more likely to have impacts on eating (OR = 1.9, 95% CI 1.4–2.7) and tooth cleaning (OR = 1.6, 95% CI 1.6–2.5).

Conclusion

Substantial proportions of students suffered from untreated dental caries, oral impacts on daily performances and perceived need for dental care. Dental pain and reported oral problems varied systematically with OIDP across the eight impacts considered. Eating and tooth cleaning problems discriminated between subjects who perceived need for dental treatment and those who did not.
Sequence diversity on four ORFs of citrus tristeza virus correlates with pathogenicity
Authors: Herrera-Isidrón Lisset , Ochoa-Sánchez Juan Carlos , Rivera-Bustamante Rafael , Martínez-Soriano Juan Pablo
Published: July 2009

The molecular characterization of isolates of citrus tristeza virus (CTV) from eight locations in Mexico was undertaken by analyzing five regions located at the opposite ends of the virus genome. Two regions have been previously used to study CTV variability (coat protein and p23), while the other three correspond to other genomic segments (p349-B, p349-C and p13). Our comparative nucleotide analyses included CTV sequences from different geographical origins already deposited in the GenBank databases. The largest nucleotide differences were located in two fragments located at the 5' end of the genome (p349-B and p349-C). Phylogenetic analyses on those five regions showed that the degree of nucleotide divergence among strains tended to correlate with their pathogenicity. Two main groups were defined: mild, with almost no noticeable effects on the indicator plants and severe, with drastic symptoms. Mild isolates clustered together in every analyzed ORF sharing a genetic distance below 0.022, in contrast with the severe isolates, which showed a more disperse distribution and a genetic distance of 0.276. Analyses of the p349-B and p349-C regions evidenced two lineages within the severe group: severe common subgroup (most of severe isolates) and severe divergent subgroup (T36-like isolates). This study represents the first attempt to analyze the genetic variability of CTV in Mexico by constructing phylogenetic trees based on new genomic regions that use group-specific nucleotide and amino acid sequences. These results may be useful to implement specific assays for strain discrimination. Moreover, it would be an excellent reference for the CTV situation in México to face the recent arrival of brown citrus aphid.
UK pneumonectomy outcome study (UKPOS): a prospective observational study of pneumonectomy outcome
Authors: Powell Ellie S , Pearce Adrian C , Cook David , Davies Paul , Bishay Ehab , Bowler Geoffrey MR , Gao Fang ,   UKPOS Co-ordinators
Published: July 2009

Background

In order to assess the short term risks of pneumonectomy for lung cancer in contemporary practice a one year prospective observational study of pneumonectomy outcome was made. Current UK practice for pneumonectomy was observed to note patient and treatment factors associated with major complications.

Methods

A multicentre, prospective, observational cohort study was performed. All 35 UK thoracic surgical centres were invited to submit data to the study. All adult patients undergoing pneumonectomy for lung cancer between 1 January and 31 December 2005 were included. Patients undergoing pleuropneumonectomy, extended pneumonectomy, completion pneumonectomy following previous lobectomy and pneumonectomy for benign disease, were excluded from the study.

The main outcome measure was suffering a major complication. Major complications were defined as: death within 30 days of surgery; treated cardiac arrhythmia or hypotension; unplanned intensive care admission; further surgery or inotrope usage.

Results

312 pneumonectomies from 28 participating centres were entered. The major complication incidence was: 30-day mortality 5.4%; treated cardiac arrhythmia 19.9%; unplanned intensive care unit admission 9.3%; further surgery 4.8%; inotrope usage 3.5%. Age, American Society of Anesthesiologists physical status ≥ P3, pre-operative diffusing capacity for carbon monoxide (DLCO) and epidural analgesia were collectively the strongest risk factors for major complications. Major complications prolonged median hospital stay by 2 days.

Conclusion

The 30 day mortality rate was less than 8%, in agreement with the British Thoracic Society guidelines. Pneumonectomy was associated with a high rate of major complications. Age, ASA physical status, DLCO and epidural analgesia appeared collectively most associated with major complications.
Contamination of equipment in emergency settings: An exploratory study with a targeted automated intervention
Authors: Obasi Chidi , Agwu Allison , Akinpelu Wale , Hammons Roger , Clark Clyde , Etienne-cummings Ralph , Hill Peter , Rothman Richard , Babalola Stella , Ross Tracy , Carroll Karen , Asiyanbola Bolanle
Published: July 2009

Background

Despite standard manual decontamination, hospital equipment remains contaminated with microorganisms, contributing to nosocomial transmission and hospital acquired infections. This has the potential to negate the effects of healthcare workers' hand-washing protocols. In order to decrease the likihood of equipment contamination, there has been a rise in the use of disposable pieces of equipment, especially non-critical disposables. However, these carry a significant cost, both a direct financial cost (running into billions of dollars), as well as a cost to the environment. This is important because we hope to contain the cost of healthcare, one way to do that, is to look to the hospitals themselves, for innovative solutions that maintain the standard of care.

Objective

To develop and evaluate the effectiveness of an simple decontamination device for use with portable hospital equipment, by comparing rates of residual contamination after use of the novel device versus those seen with standard manual decontamination methods.

Methods

The Self-cleaning Unit for the Decontamination of Small instruments (SUDS) is a user-friendly, automated instrument developed via multi-disciplinary collaboration for decontamination in the clinical area. Pre- and post- utilization of portable medical equipment in an emergency department (ED) setting were cultured. To evaluate durability of the decrease in antimicrobial contamination, objects were re-cultured 48 hours after SUDS cleaning and following re-introduction into the clinical setting.

Results

After manual decontamination, 25% (23/91) of the tested objects in the ED were found to be culture positive with clinically significant microorganisms(CSO). Fifteen percent (ED) of non-critical equipment tested had multiple organisms. Following the use of SUDS, the colonization rate decreased to 0%. Following SUDS treatment and re-introduction into the clinical settings, after 48 hours the contamination rates as reflected by the cultures remained 0%.

Conclusion

Standard non-critical equipment is contaminated with clinically significant microorganisms. The SUDS device allows for effective and durable decontamination of hospital equipment of varying sizes in the clinical area without disrupting patient care.
Understanding acute ankle ligamentous sprain injury in sports
Authors: Fong Daniel TP , Chan Yue-Yan , Mok Kam-Ming , Yung Patrick SH , Chan Kai-Ming
Published: July 2009

This paper summarizes the current understanding on acute ankle sprain injury, which is the most common acute sport trauma, accounting for about 14% of all sport-related injuries. Among, 80% are ligamentous sprains caused by explosive inversion or supination. The injury motion often happens at the subtalar joint and tears the anterior talofibular ligament (ATFL) which possesses the lowest ultimate load among the lateral ligaments at the ankle. For extrinsic risk factors to ankle sprain injury, prescribing orthosis decreases the risk while increased exercise intensity in soccer raises the risk. For intrinsic factors, a foot size with increased width, an increased ankle eversion to inversion strength, plantarflexion strength and ratio between dorsiflexion and plantarflexion strength, and limb dominance could increase the ankle sprain injury risk. Players with a previous sprain history, players wearing shoes with air cells, players who do not stretch before exercising, players with inferior single leg balance, and overweight players are 4.9, 4.3, 2.6, 2.4 and 3.9 times more likely to sustain an ankle sprain injury. The aetiology of most ankle sprain injuries is incorrect foot positioning at landing – a medially-deviated vertical ground reaction force causes an explosive supination or inversion moment at the subtalar joint in a short time (about 50 ms). Another aetiology is the delayed reaction time of the peroneal muscles at the lateral aspect of the ankle (60–90 ms). The failure supination or inversion torque is about 41–45 Nm to cause ligamentous rupture in simulated spraining tests on cadaver. A previous case report revealed that the ankle joint reached 48 degrees inversion and 10 degrees internal rotation during an accidental grade I ankle ligamentous sprain injury during a dynamic cutting trial in laboratory. Diagnosis techniques and grading systems vary, but the management of ankle ligamentous sprain injury is mainly conservative. Immobilization should not be used as it results in joint stiffness, muscle atrophy and loss of proprioception. Traditional Chinese medicine such as herbs, massage and acupuncture were well applied in China in managing sports injuries, and was reported to be effective in relieving pain, reducing swelling and edema, and restoring normal ankle function. Finally, the best practice of sports medicine would be to prevent the injury. Different previous approaches, including designing prophylactice devices, introducing functional interventions, as well as change of games rules were highlighted. This paper allows the readers to catch up with the previous researches on ankle sprain injury, and facilitate the future research idea on sport-related ankle sprain injury.
Editorial: Hemopexin: newest member of the anti-inflammatory mediator club
Authors: Fink Mitchell P
Published: July 2009

The iron-binding protein, hemopexin, down-regulates the production of proinflammatory mediators by immunostimulated-macrophages or monocytes.