bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth factor concentrations and their placental mRNA expression are modulated in gestational diabetes mellitus: possible interactions with macrosomia
Authors: Grissa Oussama , Yessoufou Akadiri , Mrisak Inès , Hichami Aziz , Amoussou-Guenou Daniel , Grissa Abir , Djrolo François , Moutairou Kabir , Miled Abdelhedi , Khairi Hédi , Zaouali Monia , Bougmiza Iheb , Zbidi Aabdelkarim , Tabka Zouheir , Khan Naim A 
Published: February 2010

Abstract

Background
Gestational diabetes mellitus (GDM) is a form of diabetes that occurs during pregnancy. GDM is a well known risk factor for foetal overgrowth, termed macrosomia which is influenced by maternal hypergycemia and endocrine status through placental circulation. The study was undertaken to investigate the implication of growth factors and their receptors in GDM and macrosomia, and to discuss the role of the materno-foeto-placental axis in the in-utero regulation of foetal growth.

Methods
30 women with GDM and their 30 macrosomic babies (4.75 ± 0.15 kg), and 30 healthy age-matched pregnant women and their 30 newborns (3.50 ± 0.10 kg) were recruited in the present study. Serum concentrations of GH and growth factors, i.e., IGF-I, IGF-BP3, FGF-2, EGF and PDGF-B were determined by ELISA. The expression of mRNA encoding for GH, IGF-I, IGF-BP3, FGF-2, PDGF-B and EGF, and their receptors, i.e., GHR, IGF-IR, FGF-2R, EGFR and PDGFR-β were quantified by using RT-qPCR.

Results
The serum concentrations of IGF-I, IGF-BP3, EGF, FGF-2 and PDGF-B were higher in GDM women and their macrosomic babies as compared to their respective controls. The placental mRNA expression of the growth factors was either upregulated (FGF-2 or PDGF-B) or remained unaltered (IGF-I and EGF) in the placenta of GDM women. The mRNA expression of three growth factor receptors, i.e., IGF-IR, EGFR and PDGFR-β, was upregulated in the placenta of GDM women. Interestingly, serum concentrations of GH were downregulated in the GDM women and their macrosomic offspring. Besides, the expression of mRNAs encoding for GHR was higher, but that encoding for GH was lower, in the placenta of GDM women than control women.

Conclusions
Our results demonstrate that growth factors might be implicated in GDM and, in part, in the pathology of macrosomia via materno-foeto-placental axis.
Comparative transfection of DNA into primary and transformed mammalian cells from different lineages
Authors: Maurisse Rosalie , De Semir David , Emamekhoo Hamid , Bedayat Babak , Abdolmohammadi Alireza , Parsi Hooman , Gruenert Dieter C 
Published: February 2010

Abstract

Background
The delivery of DNA into human cells has been the basis of advances in the understanding of gene function and the development of genetic therapies. Numerous chemical and physical approaches have been used to deliver the DNA, but their efficacy has been variable and is highly dependent on the cell type to be transfected.

Results
Studies were undertaken to evaluate and compare the transfection efficacy of several chemical reagents to that of the electroporation/nucleofection system using both adherent cells (primary and transformed airway epithelial cells and primary fibroblasts as well as embryonic stem cells) and cells in suspension (primary hematopoietic stem/progenitor cells and lymphoblasts). With the exception of HEK 293 cell transfection, nucleofection proved to be less toxic and more efficient at effectively delivering DNA into the cells as determined by cell proliferation and GFP expression, respectively. Lipofectamine and nucleofection of HEK 293 were essentially equivalent in terms of toxicity and efficiency. Transient transfection efficiency in all the cell systems ranged from 40%-90%, with minimal toxicity and no apparent species specificity. Differences in efficiency and toxicity were cell type/system specific.

Conclusions
In general, the Amaxa electroporation/nucleofection system appears superior to other chemical systems. However, there are cell-type and species specific differences that need to be evaluated empirically to optimize the conditions for transfection efficiency and cell survival.
General practitioners' opinions on how to improve treatment of mental disorders in primary health care. Interviews with one hundred Norwegian general practitioners
Authors: Mykletun Arnstein , Knudsen Ann Kristin , Tangen Tone , Øverland Simon 
Published: February 2010

Abstract

Background
Improvements in treatment of mental disorders are repeatedly called for. General practitioners (GPs) are responsible for the majority of treatment of mental disorders. Consequently, we interviewed GPs about their opinions on how treatment of mental disorders in primary health care contexts could be improved.

Methods
Among GPs affiliated within the Norwegian reimbursement system, we approached 353, and made contact with 246 GP's. One-hundred of these agreed to participate in our study, and 95 of them expressed opinions on how to improve treatment of mental disorders. The telephone interviews were based on open-ended questions, responses were transcribed continuously, and content analysis was applied. Results are presented both as frequency tables of common responses, and as qualitative descriptions and quotations of opinions.

Results
Nearly all (95%) of the GPs had suggestions on how to improve treatment of mental disorders in primary health care. Increased capacity in secondary health care was suggested by 59% of GPs. Suggestions of improved collaboration with secondary health care were also common (57%), as were improvements of GPs' skills and knowledge relevant for diagnosing and treating mental disorders (40%) and more time for patients with mental disorders in GP contexts (40%).

Conclusions
The GPs' suggestions are in line with international research and debate. It is thought-provoking that the majority of GPs call for increased capacity in secondary care, and also better collaboration with secondary care. Some GPs made comparisons to the health care system for physical disorders, which is described as better-functioning. Our study identified no simple short-term cost-effective interventions likely to improve treatment for mental disorders within primary health care. Under-treatment of mental disorders is, however, also associated with significant financial burdens.
A new therapeutic strategy for lung tissue injury induced by influenza with CR2 targeting complement inhibitior
Authors: Zhang Chuanfu , Xu Yuanyong , Jia Leili , Yang Yutao , Wang Yong , Sun Yansong , Huang Liuyu , Qiao Fei , Tomlinson Stephen , Liu Xuelin , Zhou Yusen , Song Hongbin 
Published: February 2010

AbstractBackgroundInfluenza is a respiratory disease that seriously threatens human health. In fact, influenza virus itself does not make critical contribution to mortality induced by influenza, but "cytokine storm" produced by the excessive immune response triggered by the virus can result in inflammatory reaction of lung tissues and fatal lung tissue injury, and thus increase influenza mortality. Therefore, besides antiviral drugs, immunosuppression drugs should also be included in infection treatment.Presentation of the hypothesisComplement is the center of inflammatory reaction. If complement system is over activated, the body will have strong inflammatory reaction or tissue injury, resulting in pathological process. Many studies have proved that, inflammatory injury of lung tissues caused by influenza virus is closely related to complement activation. Therefore, inhibiting complement activation can significantly reduce inflammatory injury in lung tissues. As complement is both a physiological defense and pathological damage medium, systematic inhibition may result in side effects including infection. Therefore, we design targeting complement inhibitors for complement activation sites, i.e. with CR2 as targeting vector, complement inhibitors like CD59 and Crry are targeted to inflammatory sites to specially inhibit the complement activation in local injury, thus local inflammatory reaction is inhibited.Testing the hypothesisCR2-CD59 and CR2-Crry targeting complement inhibitors are fusion-expressed, and their biological activity is examined via invivoand in vitro tests. CR2 targeting complement inhibitors are used to treat mouse influenza viral pneumonia model, with PBS treatment group as the control. The survival and lung tissue injury of the mice is observed and the effect of CR2 targeting complement inhibitors on pneumonia induced by influenza virus is evaluated.Implications of the hypothesisCR2 targeting complement inhibitors are expected to be ideal drugs for viral pneumonia.
Isolated hepatic actinomycosis: a case report
Authors: Lall Thomas , Shehab Thomas M , Valenstein Paul 
Published: February 2010

Abstract

Introduction
Actinomyces are slow growing, non-spore forming, gram-positive, branching bacilli that thrive in anaerobic and microareophilic conditions. Actinomyces are more commonly associated with oral and cervicofacial infections. Hepatic involvement in infections of the abdomen (known as isolated hepatic actinomycosis) is rare, accounting for only 5% of all cases of actinomycosis.

Case presentation
We present the case of a 75-year-old Caucasian woman with a 3-month history of night sweats, fever, chills, abdominal bloating, anorexia, weight-loss, and early satiety. The patient was found to have isolated hepatic actinomycosis infection after undergoing a laparotomy with a biopsy of the liver. The patient has now recovered.

Conclusion
Isolated hepatic actinomycosis is a rare and often overlooked etiology for a liver mass. Given its subacute presentation and nondescript symptomatology, physicians should be aware of this differential and the potential pitfalls in diagnosis and management.
Unusual presentation of eosinophilic fasciitis: two case reports and a review of the literature
Authors: Danis Ramazan , Akbulut Sami , Altintas Abdullah , Ozmen Sehmus , Ozmen Cihan Akgul 
Published: February 2010

AbstractIntroductionEosinophilic fasciitis is an uncommon disorder with unknown etiology and a poorly understood pathogenesis. We present the cases of two patients with eosinophilic fasciitis with unusual presentation, and describe the clinical characteristics and laboratory findings related to them.Case presentationThe first case involves a 29-year-old Turkish man admitted with pain, edema and induration of his right-upper and left-lower limbs. Unilateral edema and stiffness with prominent pretibial edema was noted upon physical examination. A high eosinophil count was found on the peripheral smear. The second case involves a 63-year-old Turkish man who had pain, edema, erythema, and itching on his upper and lower extremities, which developed after strenuous physical activity. He had cervical lymphadenopathy and polyarthritis upon physical examination, and rheumatoid factor and antinuclear antibody upon laboratory examination.ConclusionEosinophilic fasciitis can present with various symptoms. When patients exhibit eosinophilia, arthralgia and myalgia, eosinophilic fasciitis should be considered as a possible diagnosis.
Acute myocardial infarction as the first presentation of thyrotoxicosis in a 31-year old woman - case report
Authors: Lewandowski Krzysztof C , Rechciński Tomasz , Krzemińska-Pakuła Maria , Lewiński Andrzej 
Published: February 2010

Abstract

Abstract
A 31-year old woman, previously fit & well was admitted with pressing retrosternal chest pain and palpitations of sudden onset. Her body weight was normal (BMI 20.5 kg/m2) and there was no significant family history of cardiac disease. She smoked, however, about 15 cigarettes a day and she had been taking combined oral contraceptive pill (Cilest®) for about three years. On admission she appeared sweaty and in pain, blood pressure 130/70 mmHg, heart rate about 110/min, mild lid-lag sign. Heart sounds were normal and chest was clear. ECG revealed 2-3 mm ST segment elevations in II, III, aVF as well as V2 to V5. Troponin I was raised and she was qualified to an emergency coronary angiography. This revealed a massive spasm of left anterior descending (LAD) coronary artery that responded to intracoronary glyceryl trinitrite administration, however, with the presence of critical narrowing of the LAD apical segment with possible superimposed thrombus. Cardiac ultrasound revealed akinesis of 1/2 of apical area consistent with myocardial infarction

Treatment and progress
She was started on Aspirin, Simvastatin, and Diltiazem, but continued to have persistent tachycardia and tremor. Thyroid function tests were ordered and showed thyrotoxicosis [free T4-46.9 pmol/l (ref. range 9-25), free T3-11.9 pmol/l (2-5), TSH - 0.02 mIU/l (0.27-4.2)]. She was referred for an endocrine opinion and started on Thiamazole. Other investigations revealed elevated anti-TPO and anti-TSH receptor antibodies consistent with Graves' disease. Thrombophilia screen was negative. She had remained euthyroid on a "block & replace" regimen (Thiamazole plus L-Thyroxine) that was discontinued after 18 months. She denies any anginal symptoms, but continues to smoke against medical advice.

Conclusions
Our case highlights the possibility of development of an acute myocardial infarction in a young subject with thyrotoxicosis. We speculate that patient's smoking habit combined with subtle thyrotoxicosis-induced prothrombotic state and/or coronary-artery spasm had lead to the above-mentioned acute coronary event.
Regulation of microsomal prostaglandin E2synthase-1 and 5-lipoxygenase-activating protein/5-lipoxygenase by 4-hydroxynonenal in human osteoarthritic chondrocytes
Authors: Chen Shu-Huang , Fahmi Hassan , Shi Qin , Benderdour Mohamed 
Published: February 2010

Abstract
Introduction
This study aimed to investigate whether hydroxynonenal (HNE) depletion is responsible for the switch from cyclooxygenase-2 (COX-2) and microsomal prostaglandin E2 synthase-1 (mPGES-1) to 5-lipoxygenase-activating protein (FLAP) and 5-lipoxygenase (5-LOX).

Methods
For COX-2 and mPGES-1 studies, human osteoarthritic chondrocytes were stimulated at different incubation times (up to 24 hours) with a single or repetitive addition of 10 μM HNE to the cultures at 2-hour intervals, up to 14 hours. For 5-LOX and FLAP studies, cells were treated with a single addition of 10 μM HNE for 24 hours, 48 hours, and 72 hours in the presence or absence of naproxen (a nonspecific COX-2 inhibitor) or antibody anti-transforming growth factor-beta 1 (TGF-β1). The protein levels of COX-2, mPGES-1 and early growth response factor-1 (Egr-1) transcription factor were evaluated by western blot, and those of prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and TGF-β1 were determined with commercial kits. The levels of mPGES-1, FLAP and 5-LOX mRNA were measured by real-time RT-PCR. Transient transfection was performed to determine promoter activities of mPGES-1 and 5-LOX.

Results
Single addition of 10 μM HNE to cultured chondrocytes induced PGE2 release as well as COX-2 and mPGES-1 expression at the protein and mRNA levels, with a plateau reached respectively at 8 and 16 hours of incubation, followed by a subsequent decline. However, repeated treatments with HNE prevented the decline of COX-2 and mPGES-1 expression that occurred with a single aldehyde addition. HNE induced mPGES-1 promoter activity, possibly through transcription factor Egr-1 activation. After 48 hours, when COX-2 expression decreased, the LTB4 level rose through 5-LOX and FLAP upregulation. The addition of naproxen to cultured chondrocytes revealed that FLAP and 5-LOX regulation by HNE required PGE2 production. Furthermore, our data showed that HNE significantly induced TGF-β1 production. The addition of anti-TGF-β1 antibody reduced HNE-induced 5-LOX and FLAP expression by 40%, indicating the partial involvement of a TGF-β1-dependent mechanism.

Conclusions
Our data demonstrate that the shunt to the FLAP and 5-LOX pathway in HNE-induced human osteoarthritic chondrocytes is attributed to COX-2 and mPGES-1 inhibition, probably due to HNE depletion. PGE2 and TGF-β1 are suggested to be involved in this regulation.
Universal Poor Survival in Children With Medulloblastoma Harboring Somatic TP53 Mutations
Authors: Tabori Uri , Baskin Berivan , Shago Mary , Alon Noa , Taylor Michael D. , Ray Peter N. , Bouffet Eric , Malkin David , Hawkins Cynthia 
Published: February 2010

Purpose Medulloblastoma is the prototype of treatment success in modern pediatric neuro-oncology. Unfortunately, 20% to 30% of tumors recur despite maximal resection and multimodal therapy. Multiple biologic prognostic markers have been investigated to predict recurrences, but controversy remains regarding their clinical utility. Because p53 immunopositivity is an adverse prognostic marker in pediatric medulloblastoma and TP53 mutations are associated with chemotherapy and radiation therapy resistance, we aimed to determine the extent and role of TP53 mutations in pediatric medulloblastoma treatment failure. Patients and Methods One hundred eight of 111 consecutive patients diagnosed with medulloblastoma in our institution from 1995 to 2007 were included. Median follow-up time was 5.3 years in survivors. All samples were immunostained for p53 and erbB-2. Histologic grade and immunostaining were scored by two blinded reviewers. For 49 patients, frozen material was available for TP53 sequencing. The main outcome measures were overall and progression-free survival. Results Sixteen percent of sequenced medulloblastomas harbored a TP53 mutation. As a screening test, p53 immunohistochemistry was 100% sensitive and 83% specific for a TP53 mutation. Strikingly, all mutated tumors recurred early, and 5-year survival for average-risk patients was 0% for TP53-mutated medulloblastoma compared with 74% ± 8% for wild-type medulloblastoma (P < .0001). Furthermore, 75% of recurrences in average-risk patients were associated with TP53 mutations. On multivariate analysis, TP53 mutation status was the strongest adverse prognostic factor (hazard ratio = 10.4, P = .003). Conclusion Lack of long-term survival in TP53-mutated medulloblastomas highlights the role of TP53 mutations in medulloblastoma resistance to conventional therapies and the need for alternative treatments, and prospective validation of these findings is needed.
Cellular Histone Modification Patterns Predict Prognosis and Treatment Response in Resectable Pancreatic Adenocarcinoma: Results From RTOG 9704
Authors: Manuyakorn Ananya , Paulus Rebecca , Farrell James , Dawson Nicole A. , Tze Sheila , Cheung-Lau Gardenia , Hines Oscar Joe , Reber Howard , Seligson David B. , Horvath Steve , Kurdistani Siavash K. , Guha Chandhan , Dawson David W. 
Published: February 2010

Purpose Differences in cellular levels of histone modifications have predicted clinical outcome in certain cancers. Here, we studied the prognostic and predictive value of three histone modifications in pancreatic adenocarcinoma. Methods Tissue microarrays (TMAs) from two pancreatic adenocarcinoma cohorts were examined, including those from a 195-patient cohort from Radiation Therapy Oncology Group trial RTOG 9704, a multicenter, phase III, randomized treatment trial comparing adjuvant gemcitabine with fluorouracil and a 140-patient cohort of patients with stage I or II cancer from University of California, Los Angeles Medical Center. Immunohistochemistry was performed for histone H3 lysine 4 dimethylation (H3K4me2), histone H3 lysine 9 dimethylation (H3K9me2), and histone H3 lysine 18 acetylation (H3K18ac). Positive tumor cell staining for each histone modification was used to classify patients into low- and high-staining groups, which were related to clinicopathologic parameters and clinical outcome measures. Results Low cellular levels of H3K4me2, H3K9me2, or H3K18ac were each significant and independent predictors of poor survival in univariate and multivariate models, and combined low levels of H3K4me2 and/or H3K18ac were the most significant predictor of overall survival (hazard ratio, 2.93; 95% CI, 1.78 to 4.82) in the University of California, Los Angeles cohort. In subgroup analyses, histone levels were predictive of survival specifically for those patients with node-negative cancer or for those patients receiving adjuvant fluorouracil, but not gemcitabine, in RTOG 9704. Conclusion Cellular levels of histone modifications define previously unrecognized subsets of patients with pancreatic adenocarcinoma with distinct epigenetic phenotypes and clinical outcomes and represent prognostic and predictive biomarkers that could inform clinical decisions, including the use of fluorouracil chemotherapy.
Cost Effectiveness of Positron Emission Tomography in Patients With Hodgkin's Lymphoma in Unconfirmed Complete Remission or Partial Remission After First-Line Therapy
Authors: Cerci Juliano J. , Trindade Evelinda , Pracchia Luís F. , Pitella Felipe A. , Linardi Camila C.G. , Soares José , Delbeke Dominique , Topfer Leigh-Ann , Buccheri Valeria , Meneghetti José C. 
Published: February 2010

Purpose To assess the cost effectiveness of fluorine-18–fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with Hodgkin's lymphoma (HL) with unconfirmed complete remission (CRu) or partial remission (PR) after first-line treatment. Patients and Methods One hundred thirty patients with HL were prospectively studied. After treatment, all patients with CRu/PR were evaluated with FDG-PET. In addition, PET-negative patients were evaluated with standard follow-up, and PET-positive patients were evaluated with biopsies of the positive lesions. Local unit costs of procedures and tests were evaluated. Cost effectiveness was determined by evaluating projected annual economic impact of strategies without and with FDG-PET on HL management. Results After treatment, CRu/PR was observed in 50 (40.0%) of the 127 patients; the sensitivity, specificity, and positive and negative predictive values of FDG-PET were 100%, 92.0%, 92.3%, and 100%, respectively (accuracy of 95.9%). Local restaging costs without PET were $350,050 compared with $283,262 with PET, a 19% decrease. The incremental cost-effectiveness ratio is −$3,268 to detect one true case. PET costs represented 1% of total costs of HL treatment. Simulated costs in the 974 patients registered in the 2008 Brazilian public health care database showed that the strategy including restaging PET would have a total program cost of $56,498,314, which is $516,942 less than without restaging PET, resulting in a 1% cost saving. Conclusion FDG-PET demonstrated 95.9% accuracy in restaging for patients with HL with CRu/PR after first-line therapy. Given the observed probabilities, FDG-PET is highly cost effective and would reduce costs for the public health care program in Brazil.