bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deficiency in four and one half LIM domain protein 2 (FHL2) aggravates liver fibrosis in mice
Authors: Huss Sebastian , Stellmacher Christian , Goltz Diane , Khlistunova Inna , Adam Alexander C , Trebicka Jonel , Kirfel Jutta , Büttner Reinhard , Weiskirchen Ralf 
Published: January 2013

Abstract

Background
Four and one half LIM domain protein 2 (FHL2) has been reported to be a key regulator in many cellular processes being associated with fibrogenesis such as cell migration and contraction. Moreover, hepatic FHL2 is involved in regulation pathways mediating proliferation and cell death machineries. We here investigated the role of FHL2 in the setting of experimental and clinical liver fibrosis.

Methods
FHL2−/− and wild type (wt) mice were challenged with CCl4. Fibrotic response was assessed by quantitative real time PCR (qRT-PCR) of fibrotic marker genes, measurement of hydroxyproline content and histological methods. Murine FHL2−/− and hepatic stellate cells (HSC) were isolated and investigated via immunofluorescence. Human fibrotic and normal liver samples were analysed immunohistochemically using antibodies directed against FHL2.

Results
FHL2−/− mice displayed aggravated liver fibrosis compared to wt mice. However, immunofluorescence revealed no significant morphological changes in cultured FHL2−/− and wt myofibroblasts (MFB). In human liver samples, FHL2 was strongly expressed both in the nucleus and cytoplasm in MFB of fibrotic livers. In contrast, FHL2 expression was absent in normal liver tissue.

Conclusions
Deficiency of FHL2 results in aggravation of murine liver fibrosis. In human liver samples, FHL2 is expressed in activated HSCs and portal fibroblasts in human fibrotic livers, pointing to a central role of FHL2 for human hepatic fibrogenesis as well.
Calcification of coronary arteries and abdominal aorta in relation to traditional and novel risk factors of atherosclerosis in hemodialysis patients
Authors: Pencak Przemysław , Czerwieńska Beata , Ficek Rafał , Wyskida Katarzyna , Kujawa-Szewieczek Agata , Olszanecka-Glinianowicz Magdalena , Więcek Andrzej , Chudek Jerzy 
Published: January 2013

Abstract

Background
Process of accelerated atherosclerosis specific for uremia increases cardiovascular risk in patients with chronic kidney disease (CKD) and may be influenced by the different structure of arteries. The study assesses the influence of traditional and novel risk factors on calcification of coronary arteries (CAC) and abdominal aorta (AAC) in hemodialysis patients (HD).

Methods
CAC and AAC were assessed by CT in 104 prevalent adult HD and 14 apparently healthy subjects with normal kidney function (control group). Mineral metabolism parameters, plasma levels of FGF-23, MGP, osteoprotegerin, osteopontin, fetuin-A, CRP, IL-6 and TNF-α were measured.

Results
CAC and AAC (calcification score ≥ 1) were found in 76 (73.1%) and 83 (79.8%) HD respectively, more frequent than in the control group. In 7 HD with AAC no CAC were detected. The frequency and severity of calcifications increased with age. Both CAC and AAC were more frequently detected in diabetics (OR = 17.37 and 13.00, respectively). CAC score was significantly greater in males. CAC and AAC scores were correlated significantly with pack-years of smoking and plasma osteoprotegrin levels. However the independent contribution of plasma osteoprotegerin levels was not confirmed in multiple regression analysis. Age (OR = 1.13) and hemodialysis vintage (OR = 1.14) were the independent risk factor favoring the occurrence of CAC; while age (OR = 1.20) was the only predictor of AAC occurrence in HD.

Conclusions
1. AAC precedes the occurrence of CAC in HD patients. 2. The exposition to uremic milieu and systemic chronic microinflammation has more deteriorative effect on the CAC than the AAC.
Effect of dabrafenib on melanoma cell lines harbouring the BRAF
V600D/R
mutations
Authors: Gentilcore Giusy , Madonna Gabriele , Mozzillo Nicola , Ribas Antoni , Cossu Antonio , Palmieri Giuseppe , Ascierto Paolo A 
Published: January 2013

Abstract

Background
Conventional therapeutic agents are largely unsatisfactory into the treatment of malignant melanoma. Recently, an innovative approach based on inhibitors of the mutated BRAF gene (which represents the most prevalent alteration in melanoma patients) appears very promising from the clinical point of view. On this regard, a new compound, dabrafenib (GSK2118436), has been demonstrated to be effective in patients carrying the BRAFV600E/K mutations. We here tested dabrafenib for its capability to inhibit cell growth on primary melanoma cell lines, established from patients' tumour tissues and carrying the BRAFV600D/R mutations.

Methods
Three melanoma cell lines were tested: M257 wild-type BRAF, LCP BRAFV600R and WM266 BRAFV600D. The MTT assays were performed using standardized approaches. To evaluate the inhibition of MAPK pathway and the consequent inhibition of cellular proliferation, the phosphorylation of ERK was examined by Western Blot analysis performed on total protein extracts from cell lines after treatment with dabrafenib.

Results
Our experiments demonstrated an effective action of Dabrafenib (GSK2118436) and the inhibition of MAPK pathway in melanoma cell lines carrying BRAFV600D/R mutations.

Conclusion
These results could be helpful to enlarge the number of melanoma patients who may benefit of a more effective targeted treatment.
Study protocol: the effect of whole body vibration on acute unilateral unstable lateral ankle sprain- a biphasic randomized controlled trial
Authors: Baumbach Sebastian Felix , Fasser Mariette , Polzer Hans , Sieb Michael , Regauer Markus , Mutschler Wolf , Schieker Matthias , Blauth Michael 
Published: January 2013

AbstractBackgroundAnkle sprains often result in ankle instability, which is most likely caused by damage to passive structures and neuromuscular impairment. Whole body vibration (WBV) is a neuromuscular training method improving those impaired neurologic parameters. The aim of this study is to compare the current gold standard functional treatment to functional treatment plus WBV in patients with acute unilateral unstable inversion ankle sprains.Methods/Design60 patients, aged 18–40 years, presenting with an isolated, unilateral, acute unstable inversion ankle sprain will be included in this bicentric, biphasic, randomized controlled trial. Samples will be randomized by envelope drawing. All patients will be allowed early mobilization and pain-dependent weight bearing, limited functional immobilization by orthosis, PRICE, NSARDs as well as home and supervised physiotherapy. Supervised physical therapy will take place twice a week, for 30 minutes for a period of 6 weeks, following a standardized intervention protocol. During supervised physical therapy, the intervention group will perform exercises similar to those of the control group, on a side-alternating sinusoidal vibration platform. Two time-dependent primary outcome parameters will be assessed: short-term outcome after six weeks will be postural control quantified by the sway index; mid-term outcome after one year will be assessed by subjective instability, defined by the presence of giving-way attacks. Secondary outcome parameters include: return to pre-injury level of activities, residual pain, recurrence, objective instability, energy/coordination, Foot and Ankle Disability Index and EQ 5D.DiscussionThis is the first trial investigating the effects of WBV in patients with acute soft tissue injury. Inversion ankle sprains often result in ankle instability, which is most likely due to damage of neurological structures. Due to its unique, frequency dependent, influence on various neuromuscular parameters, WBV is a promising treatment method for patients with acute unstable inversion ankle sprains.Trial registrationNCT01702597
Focal cryosurgical ablation of the prostate: a single institute’s perspective
Authors: Hale Zachary , Miyake Makito , Palacios Diego Aguilar , Rosser Charles J 
Published: January 2013

Abstract

Background
With the stage migration of prostate cancer witnessed in the late 1990’s and early 2000’s along with the persistent morbidities associated with prostatectomy and radiation therapy, the concept of focal prostate cancer treatment remains quite attractive. Herein we evaluate the tolerability and non-oncologic outcomes of a highly select cohort of men that underwent focal cryoablation of the prostate for the treatment of localized prostate cancer.

Methods
Pre-operatively, erectile function was assessed by SHIM questionnaire while voiding symptoms were assessed by AUA symptom score. Twenty-six highly select patients (23 low-risk prostate cancer and 3 intermediate-risk prostate cancer) with documented minimal disease on saturation prostate biopsy underwent focal cryoablation of the prostate (24 hemi-ablation and 2 subtotal ablation). Subsequently, serum PSAs were obtained every 3 months for 2 years and then every 6 months thereafter. PSA failure was defined as an increase of 0.50 ng/ml over nadir. Mean follow-up was 19.1 months. Subjective assessment of erectile function and voiding was assessed post-operatively at each visit.

Results
Based on our PSA failure definition, 11.5% (3 patients) of the cohort experienced biochemical failure. In two of the three patients, localized disease was detected on subsequent transrectal ultrasound guided biopsy. These two patients went on to have favorable PSA nadirs after undergoing conventional definitive therapy (one patient had external beam radiation and one patient had whole gland cryoablation). Within the study cohort, 27% (7 patients) reported new post-operative erectile dysfunction requiring therapy while no patients reported new post-operative urinary incontinence or worsening of voiding symptoms.

Conclusion
These preliminary results add to the expanding body of literature that the minimally invasive focal cryosurgical ablation of the prostate is a safe procedure with few side effects. The true extent of cancer control remains in question, but in highly select patients, favorable PSA kinetics have been demonstrated. If confirmed by further studies with long-term follow-up, this treatment approach could have a profound effect on prostate cancer management.
The characteristics of patient safety culture in Japan, Taiwan and the United States
Authors: Fujita Shigeru , Seto Kanako , Ito Shinya , Wu Yinghui , Huang Chiu-Chin , Hasegawa Tomonori 
Published: January 2013

Abstract

Background
Quality and safety issues are receiving growing attention. Patient safety culture (PSC) plays an important role in patient safety. The characteristics of PSC in various countries, each with a different set of values, have not been determined sufficiently. The aim of this study is to investigate the characteristics of PSC in Japan, Taiwan and the U.S.

Methods
A cross-sectional survey was conducted in Japan and Taiwan using the Hospital Survey on PSC (HSOPS) questionnaire developed by the U.S. Agency for Healthcare Research and Quality (AHRQ). Data from Japan and Taiwan were also compared with the U.S. “2010 HSOPS Comparative Database” provided by AHRQ.

Results
Valid response rates in Japan, Taiwan and the U.S. were 66.5% (6,963/10,466), 85.7% (10,019/11,692) and 35.2% (291,341/827,424), respectively. The proportion of respondents with some experience of event reporting during the past 12 months was highest in Japan. In general, U.S. healthcare workers were likely to evaluate their PSC higher than that in Japan or Taiwan. The attitude of continuous improvement in Japan and event reporting of near misses in Taiwan were rated as low. In the U.S., staffing was rated as high.

Conclusions
The results suggest that PSC varies among different countries, and the cultural setting of each country should be given special consideration in the development of effective intervention plans to improve PSC. Additional investigations with improved methodology and a common protocol are required to accurately compare PSCs among countries.
Induction of human fetal hemoglobin expression by adenosine-2’,3’-dialdehyde
Authors: He Yinghong , Rank Gerhard , Zhang Miaomiao , Ju Junyi , Liu Ronghua , Xu Zhen , Brown Fiona , Cerruti Loretta , Ma Chi , Tan Renxiang , Jane Stephen M , Zhao Quan 
Published: January 2013

Abstract

Background
Pharmacologic reactivation of fetal hemoglobin expression is a promising strategy for treatment of sickle cell disease and β-thalassemia. The objective of this study was to investigate the effect of the methyl transferase inhibitor adenosine-2’,3’-dialdehyde (Adox) on induction of human fetal hemoglobin (HbF) in K562 cells and human hematopoietic progenitor cells.

Methods
Expression levels of human fetal hemoglobin were assessed by northern blot analysis and Real-time PCR. HbF and adult hemoglobin (HbA) content were analyzed using high-performance liquid chromatography (HPLC). DNA methylation levels on human gamma-globin gene promoters were determined using Bisulfite sequence analysis. Enrichment of histone marks on genes was assessed by chromosome immunoprecipitation (ChIP).

Results
Adox induced γ-globin gene expression in both K562 cells and in human bone marrow erythroid progenitor cells through a mechanism potentially involving inhibition of protein arginine methyltransferase 5 (PRMT5).

Conclusions
The ability of methyl transferase inhibitors such as Adox to efficiently reactivate fetal hemoglobin expression suggests that these agents may provide a means of reactivating fetal globin expression as a therapeutic option for treating sickle cell disease and β-thalassemia.
A closed form unwrapping method for a spherical omnidirectional view sensor
Authors: Chong Nguan Soon , Kho Yau Hee , Dennis Wong Mou Ling 
Published: January 2013

Abstract
This article proposes a novel method of image unwrapping for spherical omnidirectional images acquired through a non-single viewpoint (NSVP) omnidirectional sensor. It has three key steps i.e. (1) calibrate the camera to obtain parameters describing the spherical omnidirectional sensor, (2) map world points onto mirror points and, subsequently, onto image points, and (3) set up the projection plane for the final image unwrapping. Based on the projection plane selected, the algorithm is able to produce three common forms of unwrapping, namely cylindrical panoramic, cuboid panoramic, and ground plane view using closed form mapping equations. The motivation for developing this technique is to address the complexity in using a NSVP omnidirectional sensor and ultimately encouraging its application in robotics field. One of the main advantages of a NSVP omnidirectional sensor is that the mirror can often be obtained at a lower price as compared to the single viewpoint counterpart.
Fasting substrate oxidation in relation to habitual dietary fat intake and insulin resistance in non-diabetic women: a case for metabolic flexibility?
Authors: Carstens Madelaine T , Goedecke Julia H , Dugas Lara , Evans Juliet , Kroff Jacolene , Levitt Naomi S , Lambert Estelle V 
Published: January 2013

Abstract

Background
Metabolic flexibility described as “the capacity of the body to match fuel oxidation to fuel availability” has been implicated in insulin resistance. We examined fasting substrate oxidation in relation to dietary macronutrient intake, and markers of insulin resistance in otherwise healthy women, with and without a family history of diabetes mellitus (FH DM).

Methods
We measured body composition (dual x-ray absorptiometry), visceral and subcutaneous adipose tissue area (VAT, SAT, using Computerised Tomography), fasting [glucose], [insulin], [free fatty acids], [blood lipids], insulin resistance (HOMA-IR), resting energy expenditure (REE), respiratory exchange ratio(RER) and self-reported physical activity in a convenience sample of 180 women (18-45 yrs). A food frequency questionnaire was used to assess energy intake (EI) and calculate the RER: Food Quotient (FQ) ratio. Only those with EI:REE (1.05 -2.28) were included (N=140). Insulin resistance was defined HOMA-IR (>1.95).

Results
The Insulin Resistant (IR) group had higher energy, carbohydrate and protein intakes (p < 0.05) and lower PA levels than Insulin Sensitive (IS) group (P < 0.001), but there were no differences in RER or RER:FQ between groups. However, nearly 50% of the variance in HOMA-IR was explained by age, body fat %, VAT, RER:FQ and FH DM (adjusted R2 = 0.50, p < 0.0001). Insulin-resistant women, and those with FH DM had a higher RER:FQ than their counterparts (p < 0.01), independent of body fat % or distribution.

Conclusion
In these apparently healthy, weight-stable women, insulin resistance and FH DM were associated with lower fat oxidation in relation to dietary fat intake, suggesting lower metabolic flexibility.
Bee venom acupuncture for the treatment of chronic low back pain: study protocol for a randomized, double-blinded, sham-controlled trial
Authors: Seo Byung-Kwan , Lee Jun-Hwan , Sung Won-Suk , Song Eun-Mo , Jo Dae-Jean 
Published: January 2013

Abstract

Background
Chronic non-specific low back pain is the most common medical problem for which patients seek complementary and alternative medical treatment, including bee venom acupuncture. However, the effectiveness and safety of such treatments have not been fully established by randomized clinical trials. The aim of this study is to determine whether bee venom acupuncture is effective for improving pain intensity, functional status and quality of life of patients with chronic non-specific low back pain.

Methods/design
This study is a randomized, double-blinded, sham-controlled clinical trial with two parallel arms. Fifty-four patients between 18 and 65 years of age with non-radicular chronic low back pain experiencing low back pain lasting for at least the previous three months and ≥4 points on a 10-cm visual analog scale for bothersomeness at the time of screening will be included in the study. Participants will be randomly allocated into the real or sham bee venom acupuncture groups and treated by the same protocol to minimize non-specific and placebo effects. Patients, assessors, acupuncturists and researchers who prepare the real or sham bee venom acupuncture experiments will be blinded to group allocation. All procedures, including the bee venom acupuncture increment protocol administered into predefined acupoints, are designed by a process of consensus with experts and previous researchers according to the Standards for Reporting Interventions in Clinical Trials of Acupuncture. Bothersomeness measured using a visual analogue scale will be the primary outcome. Back pain-related dysfunction, pain, quality of life, depressive symptoms and adverse experiences will be measured using the visual analogue scale for pain intensity, the Oswestry Disability Index, the EuroQol 5-Dimension, and the Beck’s Depression Inventory. These measures will be recorded at baseline and 1, 2, 3, 4, 8 and 12 weeks.

Discussion
The results from this study will provide clinical evidence on the efficacy and safety of bee venom acupuncture in patients with chronic non-specific low back pain.

Trial registration
This study is registered with the United States National Institutes of Health Clinical Trials Registry: NCT01491321
Recommendations for the management of tyrosinaemia type 1
Authors: de Laet Corinne , Dionisi-Vici Carlo , Leonard James V , McKiernan Patrick , Mitchell Grant , Monti Lidia , de Baulny Hélène Ogier , Pintos-Morell Guillem , Spiekerkötter Ute 
Published: January 2013

Abstract
The management of tyrosinaemia type 1 (HT1, fumarylacetoacetase deficiency) has been revolutionised by the introduction of nitisinone but dietary treatment remains essential and the management is not easy. In this review detailed recommendations for the management are made based on expert opinion, published case reports and investigational studies as the evidence base is limited and there are no prospective controlled studies.
The added value of this paper is that it summarises in detail current clinical knowledge about HT1 and makes recommendations for the management.
Identification of anti-inflammatory and other biological activities of 3-carboxamide, 3-carbohydrazide and ester derivatives of gatifloxacin
Authors: Sultana Najma , Arayne M Saeed , Naz Asia , Mesaik M Ahmed 
Published: January 2013

Abstract

Background
Seventeen 1,4-dihydroquinoline-3-carboxamide and 1,4-dihydroquinoline-3-carbohydrazide derivatives of gatifloxacin have been prepared with a facile one step synthesis aiming to improve antibacterial, antifungal and immunological activities. The methodology allows the introduction of a variety of substituents such as amines, alcohol, phenol, amides and alkyl halides into the core structure of gatifloxacin.

Results
The analog N-(3-aminophenyl)-1-cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxamide has been identified as a potentially excellent anti-inflammatory agent, which exhibited highly potent effects on the oxidative burst activity of whole blood phagocytes (IC50 <12.5 μg mL-1), neutrophils (IC50 <0.1 μg mL-1) and macrophages phagocytes (IC50 <3.1 μg mL-1) as well as potent T-cell proliferation inhibitory effect (IC50 3.7 μg mL-1) while having comparable antibacterial activity to gatifloxacin. Another analog, 1-cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxo-N-phenyl-1,4-dihydroquinoline-3-carbohydrazide has tremendous T-cell proliferation inhibitory effect IC50 <3.1 μg mL-1 as compared to prednisolone, whereas, 3,5-dihydroxyphenyl1-cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate and 2-hydroxyphenyl-1-cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate envision good inhibitory activity on T-cells proliferation (IC50 6.8 & 8.8 μg mL-1 respectively).

Conclusions
The structural modification at carboxylic group has resulted in improved anti-inflammatory activities with comparable antibacterial activity to gatifloxacin. We believe that C3 structural modifications of gatifloxacin are definitely important in bringing major immunomodulatory changes in these compounds.