bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Effects of Variable Frequencies of Manual Acupuncture at St36 in Rats with Atropine-Induced Inhibition of Gastric Motility
Authors: Gao Li-Li , Guo Yi , Sha Tao , Liu Yang-Yang , Tang Jia-Bei , Yuan Fang , Zhou Tao , Hong Shou-Hai , Ming Dong 
Published: July 2015

Objective The ‘intensity-response’ relationship between acupuncture stimulation and therapeutic effect is currently the focus of much research interest. The same needling manipulation with different frequencies can generate differential levels of stimulus. This study aimed to examine the effects on gastric motility induced by four twirling frequencies based on relatively standardised manual acupuncture (MA) manipulations. Methods Twirling manipulations at 1, 2, 3, and 4 Hz were practised before the experiments by a single operator using an MA parameter measurement device and stability was evaluated through time-frequency analysis. Forty-eight Sprague-Dawley rats were randomly divided into six groups (n=8 each): Control, Model, Model+MA (1, 2, 3, and 4 Hz). Rats in the five Model groups received injections of atropine into the tail vein to inhibit gastric motility, which was continuously recorded by a balloon in the gastric antrum. Rats in the four Model+MA groups received MA at 1, 2, 3 and 4 Hz, respectively, for 70 s and needles were retained for a further 5 min. Results The amplitude of waveforms produced by the four twirling frequencies was relatively consistent and reproducible. The gastric motility amplitude in all groups decreased after modelling (injections of atropine) (p<0.01). Twirling manipulation at 1, 2, and 3 Hz (but not 4 Hz) increased gastric motility amplitude (p<0.05). The increase in gastric motility amplitude induced by MA at 2 Hz was greater than for all other frequencies (p<0.05). Conclusions Acupuncture at ST36 helped recover gastric motility amplitude in rats with atropine-induced gastric inhibition and the effects induced by 1–3 Hz frequency were greater than those induced by 4 Hz.
Inhibition of Spinal Microglia and Astrocytes Contributes to the Anti-Allodynic Effect of Electroacupuncture in Neuropathic Pain Induced by Spinal Nerve Ligation
Authors: Liang Yi , Qiu Yujie , Du Junying , Liu Jin , Fang Junfan , Zhu Ji , Fang Jianqiao 
Published: July 2015

Objective Besides neurons, activated microglia and astrocytes in the spinal cord dorsal horn (SCDH) contribute to the pathogenesis of chronic pain. Electroacupuncture (EA) has been used widely to treat various chronic pain diseases, however, the underlying mechanisms of EA are still not fully understood. Methods Male Sprague-Dawley rats were randomly divided into four groups, including an untreated healthy Control group (n=14), a True-spinal nerve ligation (SNL) group that underwent SNL and remained untreated (n=25), a True-SNL+EA group that underwent SNL followed by EA treatment (n=25), and a Sham-SNL group that underwent sham surgery and remained untreated (n=15). SNL was performed unilaterally at L5 and EA was applied to ST36 and BL60 bilaterally once per day. Paw withdrawal thresholds (PWTs) were measured ipsilaterally at baseline and 1, 3, 7, and 14 days after ligation. Activation of microglia and astrocytes in the SCDH were examined bilaterally by immunofluorescence staining, and concentrations of interleukin-1β (IL-1β) and interleukin (IL-6) were measured in the ipsilateral SCDH by ELISA. Results SNL significantly decreased PWTs and activated glial cells in the superficial laminae of the ipsilateral SCDH. In rats with SNL, glial fibrillary acidic protein (GFAP) immunoreactivity peaked at 7 days and was maintained until 14 days post-ligation, while anti-integrin alphaM (OX-42) immunoreactivity peaked at 3 days and declined gradually. EA significantly alleviated SNL-induced mechanical allodynia. Furthermore, EA reduced microglial activation (OX-42 positive ratios) in the lumbar SCDH at 3 days post-ligation and suppressed astrocyte activation (GFAP positive ratios) at all time points observed. Conclusions EA stimulation alleviates SNL-induced neuropathic pain, at least in part through inhibition of spinal glial activation. Moreover, inhibition of spinal microglia and astrocyte activation may contribute to the immediate effects and maintenance of EA analgesia, respectively.
Pitfalls in diagnosis and treatment of alveolar echinococcosis: a sentinel case series
Authors: Stojkovic M , Mickan C , Weber TF , Junghanss T 
Published: July 2015

BackgroundAlveolar echinococcosis (AE) is a neglected zoonosis presenting with focal liver lesions (FLL) with a wide range of imaging patterns resembling benign as well as malignant FLLs. Complementary serology and histopathology may be misleading.ObjectiveThe objective of our study is to highlight pitfalls leading to wrong diagnoses and harmful interventions in patients with AE.DesignThis retrospective sentinel case series analyses diagnostic and treatment data of patients with confirmed AE.Results80 patients treated between 1999 and 2014 were included in the study. In 26/80 patients treatment decisions were based on a wrong diagnosis. AE was mistaken for cystic echinococcosis (CE) in 12/26 patients followed by cholangiocellular carcinoma (CCA) in 5/26 patients; 61/80 patients had predominantly infiltrative liver lesions and 19/80 patients had a predominantly pseudocystic radiological presentation. Serology correctly differentiated betweenEchinococcus multilocularisandEchinococcus granulosusin 53/80 patients. Histopathology reports attributed the rightEchinococcus speciesin 25/58 patients but failed to differentiateE. multilocularisfromE. granulosusin 25/58 patients. Although contraindicated in AE 8/25 patients treated surgically had instillation of a protoscolicidal agent intraoperatively. One of the eight patients developed toxic cholangitis and liver failure and died 1 year after liver transplantation.ConclusionsMisclassification of AE leads to a critical delay in growth inhibiting benzimidazole treatment, surgical overtreatment and bares the risk of liver failure if protoscolicidal agents are instilled in AE pseudocysts.
Effects of drug price reduction and prescribing restrictions on expenditures and utilisation of antihypertensive drugs in Korea
Authors: Yoo Ki-Bong , Lee Sang Gyu , Park Sohee , Kim Tae Hyun , Ahn Jeonghoon , Cho Mee-Hyun , Park Eun-Cheol 
Published: July 2015

ObjectivesTo evaluate the quantitative effects of the drug price reduction on pharmaceutical expenditures and the new guidelines to restrict prescribing on drug utilisation for antihypertensive drugs.DesignWe used an interrupted time series design with the National patient sample data of Health Insurance Review and Assessment Service in South Korea.Methods54 295 participants who were with primary hypertension from the National patient sample data of Health Insurance Review and Assessment Service were included. The study period was from March 2011 to December 2013. The dependent variables were antihypertensive drug costs, antihypertensive drug cost per prescribing day, daily drug utilisation, average number of drugs per month, percentage of original drugs per prescription, drug overutilisation and prohibited combinations. Segmented regression analysis was used.ResultsThe drug price reduction reduced expenditure (US$−1.51, −10.2%), and the new guidelines reduced expenditures even more (US$−2.13; −16.2%). These policies saved US$4.22 (28%) of antihypertensive drug costs per patient in December 2013 compared to March 2012. Drug price reduction policy was introduced in April 2012. We established the policy effect by comparing it before (March 2012) with after(21 months later-December 2012). The effects of the guidelines decreased expenditures, daily drug utilisation and the average number of drugs per month more than did the drug price reduction.ConclusionsBoth policies saved money. The guidelines were more effective over time and had fewer side effects such as increasing daily drug utilisation and number of drugs than the effects of drug price reduction.
Effectiveness of community-based peer-led diabetes self-management programmes (COMP-DSMP) for improving clinical outcomes and quality of life of adults with diabetes in primary care settings in low and middle-income countries (LMIC): a systematic review and meta-analysis
Authors: Werfalli Mahmoud , Raubenheimer Peter , Engel Mark , Peer Nasheeta , Kalula Sebastiana , Kengne Andre P , Levitt Naomi S 
Published: July 2015

IntroductionGlobally, an estimated 380 million people live with diabetes today—80% in low-income and middle-income countries. The Middle East, Western Pacific, Sub-Saharan Africa and South-East Asia remain the most affected regions where economic development has transformed lifestyles, people live longer and there is an increase in the adult population. Although peer support has been used in different conditions with varied results, yet there is limited evidence to date supporting its effectiveness, particularly for individuals with diabetes. In this review, we will focus on community-based peer-led diabetes self-management programmes (COMP-DSMP) and examine the implementation strategies and diabetes-related health outcomes associated with them in LMIC primary healthcare settings.Methods and analysisIn accordance with reporting equity-focused systematic reviews PRISMA-P (preferred reporting items for systematic review and meta-analysis protocols 2015 checklist) guidelines, a systematic review with meta-analysis of randomised controlled trials (RCTs), non-randomised controlled trials, quasi-randomised controlled trials (CCTs) that involve contact with an individual or group of peers (paid or voluntary). Electronic searches will be performed in The Cochrane Library, MEDLINE, PubMed, SCOUPS, CINAHL and PsycINFO Database for the period January up to July 2000 along with manual searches in the reference lists of relevant papers. The analyses will be performed based on baseline data from RCTs, CCTs and preintervention and postintervention means or proportions will be reported for both intervention and control groups, and the absolute change from baseline will be calculated, together with 95% CIs. For dichotomous outcomes, the relative risk of the outcome will be presented compared to the control group. The risk difference will be calculated, which is the absolute difference in the proportions in each treatment group.Ethics and disseminationEthics is not required for this study, given that this is a protocol for a systematic review, which utilises published data. The findings of this study will be widely disseminated through peer-reviewed publications and conference presentations.Trial registration numberPROSPERO (2014:CRD42014007531).
Development and validation of a screening tool to predict the risk of chronic low back pain in patients presenting with acute low back pain: a study protocol
Authors: Traeger Adrian , Henschke Nicholas , Hübscher Markus , Williams Christopher M , Kamper Steven J , Maher Chris G , Moseley G Lorimer , McAuley James H 
Published: July 2015

IntroductionAround 40% of people presenting to primary care with an episode of acute low back pain develop chronic low back pain. In order to reduce the risk of developing chronic low back pain, effective secondary prevention strategies are needed. Early identification of at-risk patients allows clinicians to make informed decisions based on prognostic profile, and researchers to select appropriate participants for secondary prevention trials. The aim of this study is to develop and validate a prognostic screening tool that identifies patients with acute low back pain in primary care who are at risk of developing chronic low back pain. This paper describes the methods and analysis plan for the development and validation of the tool.Methods/analysisThe prognostic screening tool will be developed using methods recommended by the Prognosis Research Strategy (PROGRESS) Group and reported using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement. In the development stage, we will use data from 1248 patients recruited for a prospective cohort study of acute low back pain in primary care. We will construct 3 logistic regression models to predict chronic low back pain according to 3 definitions: any pain, high pain and disability at 3 months. In the validation stage, we will use data from a separate sample of 1643 patients with acute low back pain to assess the performance of each prognostic model. We will produce validation plots showing Nagelkerke R2and Brier score (overall performance), area under the curve statistic (discrimination) and the calibration slope and intercept (calibration).Ethics and disseminationEthical approval from the University of Sydney Ethics Committee was obtained for both of the original studies that we plan to analyse using the methods outlined in this protocol (Henschkeet al, ref 11-2002/3/3144; Williamset al, ref 11638).
Educational inequalities in obesity and gross domestic product: evidence from 70 countries
Authors: Kinge Jonas Minet , Strand Bjørn Heine , Vollset Stein Emil , Skirbekk Vegard 
Published: July 2015

BackgroundWe test the reversal hypothesis, which suggests that the relationship between obesity and education depends on the economic development in the country; in poor countries, obesity is more prevalent in the higher educated groups, while in rich countries the association is reversed—higher prevalence in the lower educated.MethodsWe assembled a data set on obesity and education including 412 921 individuals from 70 countries in the period 2002–2013. Gross domestic product (GDP) per capita was used as a measure of economic development. We assessed the association between obesity and GDP by education using a two-stage mixed effects model. Country-specific educational inequalities in obesity were investigated using regression-based inequality indices.ResultsThe reversal hypothesis was supported by our results in men and women. Obesity was positively associated with country GDP only among individuals with lower levels of education, while this association was absent or reduced in those with higher levels of education. This pattern was more pronounced in women than in men. Furthermore, educational inequalities in obesity were reversed with GDP; in low-income countries, obesity was more prevalent in individuals with higher education, in medium-income and high-income countries, obesity shifts to be more prevalent among those with lower levels of education.ConclusionsObesity and economic development were positively associated. Our findings suggest that education might mitigate this effect. Global and national action aimed at the obesity epidemic should take this into account.
Abstract A23: Epigenetic Cis-regulatory interactions in HIF1a-activated melanocytes
Authors: Loftus Stacie , Cronin Julie , Fufa Temesgen , McCallion Andrew , Crawford Gregory , Pavan William 
Published: July 2015

Abstract
Melanoma tumors are heterogeneous lesions that progress through distinct cellular phenotypes exhibiting either highly proliferative or invasive cell state gene expression signatures (SOX10+ vs. TGFB+ pathways, respectively) as disease progression occurs. It is appreciated that even within a single tumor, individual cells respond to hypoxic conditions through Hypoxia Inducible Factor 1a (HIF1a) activation, leading to gene expression that promotes invasive cell properties. Regulation of gene expression integrates the binding of intrinsic cell lineage factors and general transcription machinery to key cis-regulatory DNA sequences that are epigenetically defined. In order to identify the cis-regulatory sequences that are utilized in a cell's response to HIF1a activation, we have established an integrated regulatory dataset from melan-Ink4a-ARF-/- immortalized mouse melanocytes. This dataset includes Dnase1 HS regions, enhancer regions marked by H3K4me1 and EP300 co-binding, ChIP-Seq for the transcription factors HIF1a and SOX10, and RNA-SEQ datasets under proliferative and HIF1a-activated growth conditions. We are evaluating HIF1a binding regions in order to identify the cis-regulatory sequences utilized to regulate gene expression, identify the key factors engaged at these sites, and assess the role that DNA variation has in modulating factor binding and gene transcription in the switch from proliferative to hypoxic cell signaling conditions. By identifying the epigenetic cis-regulatory interactions that occur as a result of HIF1a activation, we hypothesize that we will highlight pathways important for melanoma progression that may be relevant to future therapeutics.
Citation Format: Stacie Loftus, Julie Cronin, Temesgen Fufa, Andrew McCallion, Gregory Crawford, William Pavan. Epigenetic Cis-regulatory interactions in HIF1a-activated melanocytes. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A23.
Abstract A34: MC1R signaling reduces UV mutagenesis by ATR-mediated recruitment of XPA to photolesions
Authors: Jarrett Stuart Gordon , Horrell Erin M. Wolf , Christian Perry A. , Vanover Jillian C. , Boulanger Mary C. , Zou Yue , D'Orazio John August 
Published: July 2015

Abstract
The melanocortin 1 receptor (MC1R), which signals through cAMP, is a melanocytic Gs-coupled transmembrane receptor activated by binding to its high-affinity ligand, α-melanocyte stimulating hormone (MSH). Besides influencing pigment phenotype and mediating adaptive tanning, MC1R signaling is intricately linked with genome maintenance and DNA repair. Individuals harboring loss-of-function MC1R polymorphisms are UV sensitive and melanoma-prone. We have determined that MC1R-mediated cAMP signaling promotes nucleotide excision repair (NER) in a cAMP-dependent protein kinase A (PKA)-dependent manner. PKA directly phosphorylates ataxia telangiectasia and Rad3-related protein (ATR) at Ser435 which actively recruits the key NER protein xeroderma pigmentosum complementation group A (XPA) to sites of nuclear UV photodamage, accelerating clearance of UV-induced photolesions and reducing UV mutagenesis. Loss of Ser435 within ATR prevents PKA-mediated ATR phosphorylation, disrupts ATR-XPA binding, delays recruitment of XPA to UV-damaged DNA and elevates UV-induced mutagenesis. PKA-mediated ATR phosphorylation on Ser435 appears to induce a DNA repair-specific function of ATR independent of Chk1 phosphorylation and cell cycle arrest. Importantly, MC1R signaling defects and sub-optimal DNA repair are overcome by forskolin-mediated cAMP induction in melanocytes and in whole skin. Our findings mechanistically link cAMP-PKA signaling to NER and illustrate the potential benefits of cAMP pharmacological rescue to reduce UV mutagenesis in MC1R-defective, melanoma-susceptible individuals.
Citation Format: Stuart Gordon Jarrett, Erin M. Wolf Horrell, Perry A. Christian, Jillian C. Vanover, Mary C. Boulanger, Yue Zou, John August D'Orazio. MC1R signaling reduces UV mutagenesis by ATR-mediated recruitment of XPA to photolesions. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A34.
Abstract B05: Targeting BRAF and CDK4 in BRAF mutant melanoma induces sustained tumor regression
Authors: Sheppard Karen E. , Carleen Cullinane , Kirby Laura , Waldeck Kelly , Young Richard , Martin Claire , VanArsdale Todd , Randolph Sophia , McArthur Grant A. 
Published: July 2015

Abstract
Background: The p16-cyclinD-CDK4-RB1 pathway (CDK4 pathway) is deregulated in 90% of melanomas. The main outcome of CDK4 activation is the phosphorylation and thus, inhibition of RB1 leading to G1–S cell-cycle transition. In addition, CDK4 directly phosphorylates other proteins that promote cell-cycle progression and inhibit both cell senescence and apoptosis. The MAPK/ERK pathway is deregulated in 90% of melanoma and enhances CDK4 pathway signaling through increasing cyclin D1 expression. We have previously demonstrated in a panel of melanoma cell lines that the majority of cell lines were sensitive to a CDK4/6 inhibitor (Palbociclib) and consistent with the concept of CDK4 pathway-dependent oncogene addiction, cell lines with loss of functional p16INK4A were significantly more sensitive to Palbociclib than cells with wild-type p16INK4A. We hypothesized that dual targeting the MAPK/ERK and CDK4 pathways would lead to robust inhibition of the CDK4/Cyclin D complex and consequently induce greater tumor regression than single agent treatment.
Results: In vitro, PLX4720, Palbociclib or their combination inhibited BRAF mutant melanoma cell line proliferation and clonogenic survival, however, only with the combination treatment group was a rapid sustained inhibition achieved. Enlarged flattened cells and a significant increase in SA-β-galactosidase staining indicated that the dual treatment resulted in robust cellular senescence. In a BRAFV600E mutant A375 xenograft model, Palbociclib and PLX4720 initially induced tumor regression and tumor stasis respectively, but resistance eventually developed. In contrast, in the combination treatment, tumors regressed and sustained inhibition of tumor growth was maintained. Preliminary biomarker studies indicate resistance to PLX4720 was due to reactivation MAPK/ERK pathway and resistance to Palbociclib to partial restoration of phosphorylated RB1.
Conclusions: Combination therapy of MAPK/ERK pathway inhibitors with CDK4 inhibitors is likely to be an effective treatment for BRAF mutant melanoma and in addition delay resistance to single agent targeted therapy.
Citation Format: Karen E. Sheppard, Cullinane Carleen, Laura Kirby, Kelly Waldeck, Richard Young, Claire Martin, Todd VanArsdale, Sophia Randolph, Grant A. McArthur. Targeting BRAF and CDK4 in BRAF mutant melanoma induces sustained tumor regression. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr B05.