bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIRT1 reduction causes renal and retinal injury in diabetes through endothelin 1 and transforming growth factor β1
Authors: Mortuza Rokhsana , Feng Biao , Chakrabarti Subrata 
Published: March 2015

AbstractIn diabetes, hyperglycaemia causes up‐regulation of endothelin 1 (ET‐1) and transforming growth factor beta 1 (TGF‐β1). Previously we showed glucose reduces sirtuin1 (SIRT1), a class III histone deacetylase. Here, we investigated the regulatory role of SIRT1 on ET‐1 and TGF‐β1 expression. Human microvascular endothelial cells were examined following incubation with 25 mmol/l glucose (HG) and 5 mmol/l glucose (NG) with or without SIRT1 or histone acetylase p300 overexpression or knockdown. mRNA expressions of ET‐1, TGF‐β1, SIRT1, p300 and collagen 1α(I) were examined. SIRT1 enzyme activity, ET‐1 and TGF‐β1 protein levels were measured. Histone acetylation and endothelial permeability were further investigated. Similar analyses were performed in the kidneys and retinas of SIRT1 overexpressing transgenic mice with or without streptozotocin induced diabetes. Renal functions were evaluated. In the endothelial cells (ECs), HG caused increased permeability and escalated production of ET‐1, TGF‐β1, collagen Iα(I). These cells also showed increased p300 expression, histone acetylation and reduced SIRT1 levels. These changes were rectified in the ECs following p300 silencing or by SIRT1 overexpression, whereas SIRT1 knockdown or p300 overexpression in NG mimicked the effects of HG. High ET‐1 and TGF‐β1 levels were seen in the kidneys and retinas of diabetic mice along with micro‐albuminuria and increased fibronectin protein (marker of glucose‐induced cell injury) levels. Interestingly, these detrimental changes were blunted in SIRT1 overexpressing transgenic mice with diabetes. This study showed a novel SIRT1 mediated protection against renal and retinal injury in diabetes, regulated through p300, ET‐1 and TGF‐β1.
Beneficial effects of intramyocardial mesenchymal stem cells and VEGF165 plasmid injection in rats with furazolidone induced dilated cardiomyopathy
Authors: Yu Qin , Fang Weiyi , Zhu Ning , Zheng Xiaoqun , Na Rongmei , Liu Baiting , Meng Lili , Li Zhu , Li Qianxiao , Li Xiaofei 
Published: March 2015

AbstractTo explore the impact of myocardial injection of mesenchymal stem cells (MSCs) and specific recombinant human VEGF165 (hVEGF165) plasmid on collagen remodelling in rats with furazolidone induced dilated cardiomyopathy (DCM). DCM was induced by furazolidone (0.3 mg/bodyweight (g)/day per gavage for 8 weeks). Rats were then divided into four groups: (i) PBS group (n = 18): rats received equal volume myocardial PBS injection; (ii) MSCs group (n = 17): 100 μl culture medium containing 105 MSCs were injected into four sites of left ventricular free wall (25 μl per site); (iii) GENE group (n = 18): pCMVen‐MLC2v‐EGFP‐VEGF165 plasmid [5 × 109 pfu (0.2 ml)] were injected into four sites of left ventricular free wall (0.05 ml per site)] and (iv) MSCs+GENE group (n = 17): rats received both myocardial MSCs and pCMVen‐MLC2v‐EGFP‐VEGF165 plasmid injections. After 4 weeks, cardiac function was evaluated by echocardiography. Myocardial mRNA expressions of type I, type III collagen and transforming growth factor (TGF)‐β1 were detected by RT‐PCR. The protein expression of hVEGF165 was determined by Western blot. Myocardial protein expression of hVEGF165 was demonstrated in GENE and MSCs+GENE groups. Cardiac function was improved in MSCs, GENE and MSCs+GENE groups. Collagen volume fraction was significantly reduced and myocardial TGF‐β1 mRNA expression significantly down‐regulated in both GENE and MSCs+GENE groups, collagen type I/III ratio reduction was more significant in MSCs+GENE group than in MSCs or GENE group. Myocardial MSCs and hVEGF165 plasmid injection improves cardiac function possibly through down‐regulating myocardial TGF‐β1 expression and reducing the type I/III collagen ratio in this DCM rat model.
Protein kinase B and extracellular signal‐regulated kinase contribute to the chondroprotective effect of morroniside on osteoarthritis chondrocytes
Authors: Cheng Liang , Zeng Guoqing , Liu Zejun , Zhang Bing , Cui Xu , Zhao Honghai , Zheng Xinpeng , Song Gang , Kang Jian , Xia Chun 
Published: March 2015

AbstractDespite extensive studies on the multifaceted roles of morroniside, the main active constituent of iridoid glycoside from Corni Fructus, the effect of morroniside on osteoarthritis (OA) chondrocytes remains poorly understood. Here, we investigated the influence of morroniside on cultured human OA chondrocytes and a rat experimental model of OA. The results showed that morroniside enhanced the cell viability and the levels of proliferating cell nuclear antigen expression (PCNA), type II collagen and aggrecan in human OA chondrocytes, indicating that morroniside promoted chondrocyte survival and matrix synthesis. Furthermore, different doses of morroniside activated protein kinase B (AKT) and extracellular signal‐regulated kinase (ERK) in human OA chondrocytes, and in turn, triggered AKT/S6 and ERK/P70S6K/S6 pathway, respectively. The PI3K/AKT inhibitor LY294002 or the MEK/ERK inhibitor U0126 attenuated the effect of morroniside on human OA chondrocytes, indicating that the activation of AKT and ERK contributed to the regulation of morroniside in human OA chondrocytes. In addition, the intra‐articular injection of morroniside elevated the level of proteoglycans in cartilage matrix and the thickness of articular cartilage in a rat experimental model of OA, with the increase of AKT and ERK activation. As a consequence, morroniside has chondroprotective effect on OA chondrocytes, and may have the therapeutic potential for OA treatment.
Erythema nodosum‐like lesions during BRAF inhibitor therapy: Report on 16 new cases and review of the literature
Authors: Mössner R. , Zimmer L. , Berking C. , Hoeller C. , Loquai C. , Richtig E. , Kähler K.C. , Hassel J.C. , Gutzmer R. , Ugurel S. 
Published: March 2015

AbstractImportanceBRAF inhibitors have been licensed for the therapy of BRAF‐mutated melanoma. Recently, inflammatory skin lesions clinically resembling erythema nodosum have been reported as therapy side‐effects that may lead to treatment discontinuation.ObjectiveTo identify and characterize cases with BRAF inhibitor‐associated erythema nodosum‐like inflammatory skin lesions and development of an algorithm for their management.Design and SettingRetrospective chart review of melanoma patients treated with BRAF inhibitors in 14 departments of Dermatology in Germany and Austria and PubMed search for cases in the literature.ResultsSixteen patients were identified who developed erythema nodosum‐like lesions under BRAF inhibitor therapy; 14 had received vemurafenib and two dabrafenib plus trametinib. The most frequently involved body sites were the legs. Histopathology was performed in five cases and revealed panniculitis in three and vasculitis in two patients respectively. Arthralgia and fever were associated symptoms in 44% and 31% of patients respectively. Inflammatory symptoms led to discontinuation of treatment in three patients, while in the majority of cases symptomatic management was sufficient. Skin lesions finally resolved despite continued BRAF inhibitor therapy in seven patients. In the literature, 19 additional patients with similar cutaneous appearance under BRAF inhibitors could be identified. An algorithm for the management of such lesions is proposed.ConclusionErythema nodosum‐like skin lesions histologically correspond to panniculitis and/or vasculitis. Symptomatic treatment may be sufficient. However, additional work‐up and interruption of BRAF inhibitor therapy may be necessary in severe cases which are commonly associated with systemic symptoms.
The Clinical Course of Pain and Function in Older Adults with a New Primary Care Visit for Back Pain
Authors: Rundell Sean D. , Sherman Karen J. , Heagerty Patrick J. , Mock Charles N. , Jarvik Jeffrey G. 
Published: March 2015

ObjectivesTo report the clinical course of older adults presenting for a new primary care visit for back pain, no healthcare visit for back pain within the prior 6 months, by describing pain intensity, disability, pain interference, and resolution of back pain over 12 months.DesignProspective inception cohort study.SettingPrimary care settings of three integrated healthcare systems in the United States that participated in the Back pain Outcomes using Longitudinal Data (BOLD) registry.ParticipantsFive thousand two hundred eleven (99.5%) of the 5,239 adults aged 65 and older who had reached their 12‐month follow‐up date.MeasurementsBaseline demographic characteristics, EQ‐5D score, duration of back pain, expectation for recovery, depression, and anxiety. Participant‐reported outcomes of back‐related disability (Roland Morris Disability Questionnaire), numerical pain rating scale, pain interference, and resolution of back pain were collected at baseline and 3, 6, and 12 months.ResultsMost improvement occurred within the first 3 months. The number and proportion with 30% improvement in back pain increased from 1,950 (42.3%) at 3 months to 1,994 (44.8%) by 12 months, and 1,331 (28.8%) and 1,576 (35.4%) had 30% improvement in disability at 3 and 12 months. Only 23.0% reported that their back pain had resolved at 12 months. Improvements in disability and interference with activity over 12 months differed according to age, duration of back pain, symptoms of depression and anxiety, and expectation for recovery.ConclusionThe majority of older adults in primary care practice settings presenting with a new visit for back pain have persistent symptoms, disability, and interference over 12 months of follow‐up. Future research is needed to identify risk factors for persistent symptoms and effective interventions.
The Elderhaus Program of All‐inclusive Care for the Elderly in North Carolina: Improving Functional Outcomes and Reducing Cost of Care: Preliminary Data
Authors: Fretwell Marsha D. , Old Jane S. , Zwan Kay , Simhadri Kiran 
Published: March 2015

The Program of All‐inclusive Care for the Elderly (PACE) is at a crossroads in its evolution as a community‐based alternative to institutionally based nursing home care. Because of their perceived value and cost savings to Medicaid and Medicare, PACE programs are under increasing pressure to expand the numbers of individuals they serve while simultaneously reducing the overall cost of care. During the first 5 years of operations, the Elderhaus PACE Program in Wilmington, North Carolina, has reduced use of acute hospital care and skilled nursing home care while demonstrating that 46% of their participants improved and 20% of participants maintained their level of functional independence. It is felt that use of a plan of care organized according to standard domains of function and the quantifiable method of documenting improvement in functional health outcomes represent a critical factor in improved outcomes despite lower use of costly hospital and institutional care. The next step will be to disseminate the plan of care process to other PACE programs and measure its effect on participant functional outcomes and cost of care. The fact that the majority of PACE programs in North Carolina are using an electronic medical record that has the standard domains and quantitative functional measures embedded in the software will facilitate this step. Benchmarks for service use data are already being collected and will be compared with service use after the implementation of the plan of care process.
Temporal Aspects in Evaluating the Greenhouse Gas Mitigation Benefits of Using Residues from Forest Products Manufacturing Facilities for Energy Production
Authors: Gaudreault Caroline , Miner Reid 
Published: March 2015

SummaryMethods for carbon footprinting typically combine all emissions into a single result, representing the emissions of greenhouse gases (GHGs) over the life cycle. The timing of GHG impacts, however, has become a matter of significant interest. In this study, two approaches are used to characterize the timing of GHG emission impacts associated with the production of energy from various biomass residues produced by the forest products industry. The first approach accounts for the timing of emissions and characterizes the impact using Intergovernmental Panel on Climate Change (IPCC) 100‐year global warming potentials (GWPs). The second is a dynamic carbon footprint approach that considers the timing of the GHG emissions, their fate in the atmosphere, and the associated radiative forcing as a function of time. The two approaches generally yield estimates of cumulative impacts over 100 years that differ by less than 5%. The timing of impacts, however, can be significantly affected by the approach used to characterize radiative forcing. For instance, the time required to see net benefits from a system using woody mill residues (e.g., bark and sawdust) is estimated to be 1.2 years when using a fully dynamic approach, compared to 7.5 years when using 100‐year GWPs, with the differences being primarily attributable to methane (CH4). The results obtained for a number of different biomass residue types from forest products manufacturing highlight the importance of using a fully dynamic approach when studying the timing of emissions impacts in cases where emissions are distributed over time or where CH4 is a significant contributor to the emissions.
Considerations for Altering Preparation Designs of Porcelain Inlay/Onlay Restorations for Nonvital Teeth
Authors: Homsy Foudda , Eid Rita , El Ghoul Wiam , Chidiac Jose Johann 
Published: March 2015

AbstractPurposeThe aim of this study was to compare all ceramic inlay/onlay survival rates in vital and nonvital teeth having the same cavity design. Filling the pulp chamber with ceramic materials or not was also discussed.Materials and MethodsCeramic class II inlays/onlays were made on 11 premolars and 30 molars: 14 vital, 27 endodontically treated. The same tooth preparation design was performed on vital and nonvital teeth: In nonvital teeth the pulp chambers were covered by a glass ionomer cement until the pulpal floor depths were between 2 and 2.5 mm, more likely similar to the vital teeth preparations. In vital teeth, glass ionomer was used as a liner to achieve pulpal floor depths between 2 and 2.5 mm when needed. The restorations were assessed (at baseline, 6 months, 1 and 2 years) according to three criteria: marginal discoloration, marginal integrity, and fracture of teeth/restorations, consistent with United States Public Health Service (USPHS) criteria.ResultsEight teeth (19%) showed minor marginal discolorations, while three molars (7%) had loss of marginal integrity. These margins were adjusted using rubber polishing cups and were then judged clinically acceptable. From these three molars, one was vital and two were endodontically treated. No fracture of teeth or restorations was observed. Chi square and exact probability tests were used. There was no statistical difference between vital and nonvital teeth (p = 0.719 chi‐squared and Fisher) or between premolars and molars (p = 0.564 chi‐squared; 1.000, Fisher).ConclusionWithin the limitations of this study there was no difference for the same inlay/onlay cavity design between vital and nonvital teeth. In nonvital teeth, it seems that filling the pulp chamber with a ceramic core material is not important. Long‐term observation periods are needed to reinforce the clinical behavior outcome.
Expression and cellular localization of the transcription factorNeuroD1 in the developing and adult rat pineal gland
Authors: Castro Analía E. , Benitez Sergio G. , Farias Altamirano Luz E. , Savastano Luis E. , Patterson Sean I. , Muñoz Estela M. 
Published: March 2015

AbstractCircadian rhythms govern many aspects of mammalian physiology. The daily pattern of melatonin synthesis and secretion is one of the classic examples of circadian oscillations. It is mediated by a class of neuroendocrine cells known as pinealocytes which are not yet fully defined. An established method to evaluate functional and cytological characters is through the expression of lineage‐specific transcriptional regulators. NeuroD1 is a basic helix‐loop‐helix transcription factor involved in the specification and maintenance of both endocrine and neuronal phenotypes. We have previously described developmental and adult regulation of NeuroD1 mRNAin the rodent pineal gland. However, the transcript levels were not influenced by the elimination of sympathetic input, suggesting that any rhythmicity of NeuroD1 might be found downstream of transcription. Here, we describe NeuroD1 protein expression and cellular localization in the rat pineal gland during development and the daily cycle. In embryonic and perinatal stages, protein expression follows the mRNApattern and is predominantly nuclear. Thereafter, NeuroD1 is mostly found in pinealocyte nuclei in the early part of the night and in cytoplasm during the day, a rhythm maintained into adulthood. Additionally, nocturnal nuclear NeuroD1 levels are reduced after sympathetic disruption, an effect mimicked by the in vivo administration ofα‐ andβ‐adrenoceptor blockers. NeuroD1 phosphorylation at two sites, Ser274and Ser336, associates with nuclear localization in pinealocytes. These data suggest that NeuroD1 influences pineal phenotype both during development and adulthood, in an autonomic and phosphorylation‐dependent manner.
A novel intracellular nitrogen‐fixing symbiosis made by Ustilago maydis and Bacillus spp.
Authors: Ruiz‐Herrera José , León‐Ramírez Claudia , Vera‐Nuñez Antonio , Sánchez‐Arreguín Alejandro , Ruiz‐Medrano Roberto , Salgado‐Lugo Holjes , Sánchez‐Segura Lino , Peña‐Cabriales Juan José 
Published: March 2015

Summary

We observed that the maize pathogenic fungus Ustilago maydis grew in nitrogen (N)‐free media at a rate similar to that observed in media containing ammonium nitrate, suggesting that it was able to fix atmospheric N2. Because only prokaryotic organisms have the capacity to reduce N2, we entertained the possibility that U. maydis was associated with an intracellular bacterium.

The presence of nitrogenase in the fungus was analyzed by acetylene reduction, and capacity to fix N2 by use of 15N2. Presence of an intracellular N2‐fixing bacterium was analyzed by PCR amplification of bacterial 16S rRNA and nifH genes, and by microscopic observations.

Nitrogenase activity and 15N incorporation into the cells proved that U. maydis fixed N2. Light and electron microscopy, and fluorescence in situ hybridization (FISH) experiments revealed the presence of intracellular bacteria related to Bacillus pumilus, as evidenced by sequencing of the PCR‐amplified fragments.

These observations reveal for the first time the existence of an endosymbiotic N2‐fixing association involving a fungus and a bacterium.
Impact of weight bias and stigma on quality of care and outcomes for patients with obesity
Authors: Phelan S. M. , Burgess D. J. , Yeazel M. W. , Hellerstedt W. L. , Griffin J. M. , van Ryn M. 
Published: March 2015

SummaryThe objective of this study was to critically review the empirical evidence from all relevant disciplines regarding obesity stigma in order to (i) determine the implications of obesity stigma for healthcare providers and their patients with obesity and (ii) identify strategies to improve care for patients with obesity. We conducted a search of Medline and PsychInfo for all peer‐reviewed papers presenting original empirical data relevant to stigma, bias, discrimination, prejudice and medical care. We then performed a narrative review of the existing empirical evidence regarding the impact of obesity stigma and weight bias for healthcare quality and outcomes. Many healthcare providers hold strong negative attitudes and stereotypes about people with obesity. There is considerable evidence that such attitudes influence person‐perceptions, judgment, interpersonal behaviour and decision‐making. These attitudes may impact the care they provide. Experiences of or expectations for poor treatment may cause stress and avoidance of care, mistrust of doctors and poor adherence among patients with obesity. Stigma can reduce the quality of care for patients with obesity despite the best intentions of healthcare providers to provide high‐quality care. There are several potential intervention strategies that may reduce the impact of obesity stigma on quality of care.
Paediatric non‐alcoholic fatty liver disease: an overview
Authors: AlKhater S. A. 
Published: March 2015

SummaryNon‐alcoholic fatty liver disease (NAFLD) is a progressive disease that encompasses a spectrum of liver diseases, ranging from simple steatosis to non‐alcoholic steatohepatitis (NASH). Data related to survival in children are scarce, but these data firmly associate NAFLD with higher risks of hepatic and non‐hepatic morbidities and mortalities compared with the general population. More recently, the association between NAFLD and cardiovascular disease among children has increasingly been recognized. Given that obesity is a major risk factor for the disease, paediatric NAFLD is becoming a global issue, paralleling the dramatic rise in obesity worldwide. NASH, which is more common in obese children, has the potential to advance to liver fibrosis and failure. It is unclear why certain patients undergo such transformation but this susceptibility is likely related to an interaction between a genetically susceptible host and the surrounding environment. Currently, treatment is largely conservative and includes lifestyle modification, attainable through healthy weight reduction via diet and exercise. In this review, current knowledge about NAFLD in children is summarized. This review aims to increase the awareness of the medical community about a hidden public health issue and to identify current gaps in the literature while providing directions for future research.
A dose‐response meta‐analysis of the impact of body mass index on stroke and all‐cause mortality in stroke patients: a paradox within a paradox
Authors: Bagheri M. , Speakman J. R. , Shabbidar S. , Kazemi F. , Djafarian K. 
Published: March 2015

SummaryThe obesity paradox is often attributed to fat acting as a buffer to protect individuals in fragile metabolic states. If this was the case, one would predict that the reverse epidemiology would be apparent across all causes of mortality including that of the particular disease state. We performed a dose‐response meta‐analysis to assess the impact of body mass index (BMI) on all‐cause and stroke‐specific mortality among stroke patients. Data from relevant studies were identified by systematically searching PubMed, OVID and Scopus databases and were analysed using a random‐effects dose‐response model. Eight cohort studies on all‐cause mortality (with 20,807 deaths of 95,651 stroke patients) and nine studies of mortality exclusively because of stroke (with 8,087 deaths of 28,6270 patients) were evaluated in the meta‐analysis. Non‐linear associations of BMI with all‐cause mortality (P < 0.0001) and mortality by stroke (P = 0.05) were observed. Among overweight and obese stroke patients, the risk of all‐cause mortality increased, while the risk of mortality by stroke declined, with an increase in BMI. Increasing BMI had opposite effects on all‐cause mortality and stroke‐specific mortality in stroke patients. Further investigations are needed to examine how mortality by stroke is influenced by a more accurate indicator of obesity than BMI.