bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of statin use with peripheral neuropathy in the US population 40 years of age or older (美国40岁及以上人群的他汀使用情况与周围神经病变的关系)
Authors: Tierney Edward F. , Thurman David J. , Beckles Gloria L. , Cadwell Betsy L. 
Published: November 2012

AbstractBackgroundPeripheral neuropathy is a serious complication of diabetes and several conditions that may lead to the loss of lower extremity function and even amputations. Since the introduction of statins, their use has increased markedly. Recent reports suggest a role for statins in the development of peripheral neuropathy. The aims of the present study were to assess the association between statin use and peripheral neuropathy, and to determine whether this association varied by diabetes status.MethodsData from the lower extremity examination supplement of the 1999–2004 National Health and Nutrition Examination Survey were used.ResultsThe overall prevalence of statin use was 15% and the prevalence of peripheral neuropathy was 14.9%. The prevalence of peripheral neuropathy was significantly higher among those who used statins compared with those who did not (23.5% vs 13.5%, respectively; P < 0.01). Multivariate logistic regression revealed that statin use (adjusted odds ratio 1.3; 95% confidence interval 1.1–1.6; Wald P = 0.04) was significantly associated with peripheral neuropathy, controlling for diabetes status, age, gender, race, height, weight, blood lead levels, poverty, glycohemoglobin, use of vitamin B12, alcohol abuse, hypertension, and non‐high‐density lipoprotein–cholesterol. Diabetes status, age, gender, height, weight, blood lead levels, poverty, and glycohemoglobin were also significantly associated with peripheral neuropathy. We found no effect modification between statin use and diabetes status, race, gender, age, vitamin B12, blood lead levels, or alcohol abuse.ConclusionsIn the present cross‐sectional study, we found a modest association between peripheral neuropathy and statin use. Prospective studies are required to determine the causal direction.
Hypertension Management: Rationale for Triple Therapy Based on Mechanisms of Action
Authors: Neutel Joel M. , Smith David H. G. 
Published: November 2012

SummaryAn estimated 25% of patients will require 3 antihypertensive agents to achieve blood pressure (BP) control; combination therapy is thus an important strategy in hypertension treatment. This review discusses the triple‐therapy combination of an angiotensin receptor blocker (ARB) or direct renin antagonist (DRI) with a calcium channel blocker (CCB) and a diuretic, with a focus on mechanisms of action. Multiple physiologic pathways contribute to hypertension. Combining antihypertensive agents not only better targets the underlying pathways, but also helps blunt compensatory responses that may be triggered by single‐agent therapy. DRIs and ARBs target the renin–angiotensin–aldosterone system (RAAS) at the initial and final steps, respectively, and both classes lower BP by reducing the effects of angiotensin‐2; however, ARBs may trigger a compensatory increase in renin activity. Dihydropyridine CCBs target L‐type calcium channels and lower BP through potent vasodilation, but can trigger compensatory activation of the sympathetic nervous system (SNS) and RAAS. Thiazide diuretics lower BP initially through sodium depletion and plasma volume reduction, followed by total peripheral resistance reduction, but can also trigger compensatory activation of the SNS and RAAS. The combination of an agent targeting the RAAS with a CCB and diuretic is rational, and triple combinations of valsartan/amlodipine/hydrochlorothiazide, olmesartan/amlodipine/hydrochlorothiazide, and aliskiren/amlodipine/hydrochlorothiazide have demonstrated greater effectiveness compared with their respective dual‐component combinations. In addition, single‐pill, fixed‐dose combinations can address barriers to BP control including clinical inertia and poor adherence. Fixed‐dose antihypertensive combination products capitalize on complementary mechanisms of action and have been shown to result in improved BP control.
Modulation of methuselah expression targeted to Drosophila insulin‐producing cells extends life and enhances oxidative stress resistance
Authors: Gimenez Luis E. D. , Ghildyal Parakashtha , Fischer Kathleen E. , Hu Hongxiang , Ja William W. , Eaton Benjamin A. , Wu Yimin , Austad Steven N. , Ranjan Ravi 
Published: November 2012

SummaryUbiquitously reduced signaling via Methuselah (MTH), a G‐protein‐coupled receptor (GPCR) required for neurosecretion, has previously been reported to extend life and enhance stress resistance in flies. Whether these effects are due to reduced MTH signalling in specific tissues remains unknown. We determined that reduced expression of mth targeted to the insulin‐producing cells (IPCs) of the fly brain was sufficient to extend life and enhance oxidative stress resistance. Paradoxically, we discovered that overexpression of mth targeted to the same cells has similar phenotypic effects to reduced expression due to MTH's interaction with β‐arrestin, which uncouples GPCRs from their G‐proteins. We confirmed the functional relationship between MTH and β‐arrestin by finding that IPC‐targeted overexpression of β‐arrestin alone mimics the longevity phenotype of reduced MTH signaling. As reduced MTH signaling also inhibits insulin secretion from the IPCs, the most parsimonious mechanistic explanation of its longevity and stress‐resistance enhancement might be through reduced insulin/IGF signaling (IIS). However, examination of phenotypic features of long‐lived IPC‐mth modulated flies as well as several downstream IIS targets implicates enhanced activity of the JNK stress‐resistance pathway more directly than insulin signaling in the longevity and stress‐resistance phenotypes.
Earnings management of initial public offering firms: evidence from regulation changes in China
Authors: Liu Jianlei , Uchida Konari , Gao Ruidong 
Published: November 2012

AbstractDiscretionary current accruals of Chinese initial public offering (IPO) firms decreased after the abolition of fixed‐price offering systems that directly linked offering price to reported earnings. Results suggest IPO firms that decrease managerial ownership manage earnings upward during the fixed‐price offering period, but this relationship disappeared after the introduction of a book‐building system. We also find that bank debt is negatively related to discretionary current accruals during the fixed‐price offering period, but no relation exists for the book‐building period. Leverage has a significant positive relationship with earnings management. However, this finding is potentially attributable to nonoffering price objectives or endogeneity biases.
Root discolouration following short‐term application of steroid medicaments containing clindamycin, doxycycline or demeclocycline
Authors: Chen Belinda Kuan‐Jung , George Roy , Walsh Laurence James 
Published: November 2012

AbstractDiscolouration of teeth following application of intra‐canal antibiotic pastes is a clinical concern. This laboratory study compared the extent of tooth discolouration from three antibiotic pastes over 4 weeks. A total of 120 root samples were prepared and the canals filled with either Ledermix (demeclocyline), Odontopaste (clindamycin) or DoxyPaste (doxycycline). Roots were photographed before and 2 or 4 weeks after incubation at 37°C and 100% humidity in complete darkness in opaque containers. Digital images were standardised and assessed for changes in luminosity. Ledermix paste caused the most discolouration of the three, at both 2 and 4 weeks. There was no significant difference between DoxyPaste and Odontopaste at 2 weeks, whereas at 4 weeks, DoxyPaste caused a greater decrease in luminosity (P < 0.05), darkening more over the second 2‐week interval than treatment with Odontopaste (P < 0.05). Under zero light conditions, staining with Ledermix can still occur; indicating non‐light‐based chemical reactions in the staining process. Doxycycline containing intra‐canal medicaments caused less staining despite being a tetracycline‐based medicament.
Adrenomedullin attenuates vascular calcification in fructose‐induced insulin resistance rats
Authors: Zhou Y.‐B. , Gao Q. , Li P. , Han Y. , Zhang F. , Qi Y.‐F. , Tang C.‐S. , Gao X.‐Y. , Zhu G.‐Q. 
Published: November 2012

AbstractAimTo determine the therapeutic effects of adrenomedullin (ADM) on vascular calcification and related molecular mechanism in fructose‐induced insulin resistance rats.MethodsRats received ordinary drinking water or 10% fructose in drinking water for 12 weeks and subcutaneous injection of normal saline or ADM (3.6 μg kg−1) twice a day for the last 4 weeks. Levels of ADM, calcitonin receptor‐like receptors (CRLR), receptor activity‐modifying proteins (RAMP) as well as calcium content, alkaline phosphatase (ALP) activity, osteoblastic and contractile smooth muscle markers in aortic media were measured.ResultsThe levels of ADM, CRLR, RAMP2 and RAMP3 in aortic media were increased in fructose‐fed rats. ADM treatment attenuated the fructose‐induced insulin resistance, increased blood pressure, fasting glucose, insulin, triglycerides and cholesterol levels. It improved VSMCs proliferation and disordered arrangement and hyperplasia of elastic fibres in fructose‐fed rats. Calcium deposits, calcium content and ALP activity in the aortic media were increased in fructose‐fed rats, which were attenuated by ADM treatment. The osteoblastic markers such as osteopontin (OPN), bone morphogenetic protein 2 (BMP2) proteins and core binding factor alpha‐1 (Cbfα‐1) protein and mRNA expressions were increased in fructose‐fed rats. ADM treatment increased the OPN protein expression, but reduced the BMP2 protein, Cbfα‐1 protein and mRNA expression. Contractile smooth muscle markers such as α‐actin and smooth muscle 22α (SM‐22α) were downregulated in fructose‐fed rats, which were recovered by ADM treatment.ConclusionAdministration of ADM attenuates insulin resistance, calcium deposition and osteogenic transdifferentiation in aortic media in fructose‐fed rats.
Hydrogen water consumption prevents osteopenia in ovariectomized rats
Authors: Guo Ji‐Dong , Li Li , Shi Ya‐Min , Wang Hua‐Dong , Hou Shu‐Xun 
Published: November 2012

Background and PurposeAccumulating evidence indicates an important role of oxidative stress in the progression of osteoporosis. Recently, it was demonstrated that hydrogen gas, as a novel antioxidant, could selectively reduce hydroxyl radicals and peroxynitrite anion to exert potent therapeutic antioxidant activity. The aim of the present work was to investigate the effect of hydrogen water (HW) consumption on ovariectomy‐induced osteoporosis.Experimental ApproachOvariectomized rats were fed with HW (1.3 ± 0.2 mg·L−1) for 3 months. Then, blood was collected and femur and vertebrae were removed for evaluation of the effect of HW on bone.Key ResultsHW consumption in ovariectomized rats had no significant effect on oestrogen production, but prevented the reduction of bone mass including bone mineral content and bone mineral density in femur and vertebrae, and preserved mechanical strength including ultimate load, stiffness, and energy, and bone structure including trabecular bone volume fraction, trabecular number, and trabecular thickness in femur, and preserved mechanical strength including ultimate load and stiffness, and bone structure including trabecular bone volume fraction and trabecular number in vertebrae. In addition, treatment with HW abated oxidative stress and suppressed IL‐6 and TNF‐α mRNA expressions in femur of ovariectomized rats; treatment with HW increased femur endothelial NOS activity and enhanced circulating NO level in ovariectomized rats.Conclusions and ImplicationsHW consumption prevents osteopenia in ovariectomized rats possibly through the ablation of oxidative stress induced by oestrogen withdrawal.
Cannabidiolic acid prevents vomiting in Suncus murinus and nausea‐induced behaviour in rats by enhancing 5‐HT1A receptor activation
Authors: Bolognini D , Rock EM , Cluny NL , Cascio MG , Limebeer CL , Duncan M , Stott CG , Javid FA , Parker LA , Pertwee RG 
Published: November 2012

Background and PurposeTo evaluate the ability of cannabidiolic acid (CBDA) to reduce nausea and vomiting and enhance 5‐HT1A receptor activation in animal models.Experimental ApproachWe investigated the effect of CBDA on (i) lithium chloride (LiCl)‐induced conditioned gaping to a flavour (nausea‐induced behaviour) or a context (model of anticipatory nausea) in rats; (ii) saccharin palatability in rats; (iii) motion‐, LiCl‐ or cisplatin‐induced vomiting in house musk shrews (Suncus murinus); and (iv) rat brainstem 5‐HT1A receptor activation by 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT) and mouse whole brain CB1 receptor activation by CP55940, using [35S]GTPγS‐binding assays.Key ResultsIn shrews, CBDA (0.1 and/or 0.5 mg·kg−1 i.p.) reduced toxin‐ and motion‐induced vomiting, and increased the onset latency of the first motion‐induced emetic episode. In rats, CBDA (0.01 and 0.1 mg·kg−1 i.p.) suppressed LiCl‐ and context‐induced conditioned gaping, effects that were blocked by the 5‐HT1A receptor antagonist, WAY100635 (0.1 mg·kg−1 i.p.), and, at 0.01 mg·kg−1 i.p., enhanced saccharin palatability. CBDA‐induced suppression of LiCl‐induced conditioned gaping was unaffected by the CB1 receptor antagonist, SR141716A (1 mg·kg−1 i.p.). In vitro, CBDA (0.1–100 nM) increased the Emax of 8‐OH‐DPAT.Conclusions and ImplicationsCompared with cannabidiol, CBDA displays significantly greater potency at inhibiting vomiting in shrews and nausea in rats, and at enhancing 5‐HT1A receptor activation, an action that accounts for its ability to attenuate conditioned gaping in rats. Consequently, CBDA shows promise as a treatment for nausea and vomiting, including anticipatory nausea for which no specific therapy is currently available.
Caregiving, single parents and cumulative stresses when caring for a child with cancer
Authors: Granek L. , Rosenberg‐Yunger Z. R. S. , Dix D. , Klaassen R. J. , Sung L. , Cairney J. , Klassen A. F. 
Published: November 2012

AbstractBackgroundSingle parents whose children have cancer are a marginalized group who report less family centred care, and therefore, less quality cancer care for their children. As such, the aims of this study were to explore how single parents of children with cancer describe their caregiving experiences and to understand their contextual life stressors.MethodsA constructivist grounded theory method was used. Qualitative interviews with 29 single parents of children with cancer who were at least 6 months post‐diagnosis were recruited between November 2009 and April 2011 from four hospitals across Canada. Line‐by‐line coding was used to establish codes and themes and constant comparison was used to establish relationships among emerging codes and conceptual themes.ResultsThe first set of findings report on caregiving duties including: emotional tasks, informational tasks and physical tasks. The second set of findings report on the contextual picture of parent's lives including their living conditions, their physical and mental health and their family histories of disruption, trauma and disease.ConclusionsSingle parents caring for children with cancer were found to experience several cumulative stressors in addition to the current strain of caring for a child with cancer. The synergy of these cumulative stresses with the added strain of caregiving for a child with cancer may have long‐term health and financial implications for parents. Broad‐based policy interventions should focus on relieving the chronic strains associated with being a single parent of a child with cancer.
Tackling child health inequalities due to deprivation: using health equity audit to improve and monitor access to a community paediatric service
Authors: Maharaj V. , Rahman F. , Adamson L. 
Published: November 2012

AbstractBackgroundDeprived children constitute a large population with high levels of ill health, and difficulty with access to healthcare contributes to their poor health outcomes. There is debate on how best to engage deprived families and the literature on differential access to paediatric care based on deprivation is limited.Aims
To demonstrate that community paediatrics can contribute to reduction of health inequalities by providing services that are accessible to and preferentially used by children whose health is likely to be affected by deprivation.
To provide a template for others to improve and monitor equity in their services.
MethodLong‐term service reconfiguration and health equity audit. We used routinely collected activity data and the Indices of Multiple Deprivation to construct equity profiles of the children using our service, and compared these with the profile of the population aged 0–16 years in the geographical area covered by the service.ResultsThe new patient contact rate for the most deprived children in the population was more than three times that of the least deprived [odds ratio (OR) 3.29, 95% confidence interval (CI) 2.76–3.93]. Deprived children were more than twice as likely to require multi‐agency meetings as part of their medical care (OR 2.28, 95% CI 1.94–2.69). Seventy per cent (3693/5312) of our total contacts were with children in the two most deprived quintiles. There was a marked socio‐economic gradient in all types of contact.ConclusionsThe model of care used by our community paediatric service successfully engages deprived families, thereby reducing health inequalities due to poor access. Key features are multi‐agency working, removing barriers to access, raising staff awareness and use of health equity audit. Our findings provide support for tackling health inequalities via health services that are available to all, but capable of responding proportionately according to level of need, a model recently described as proportionate universalism.
Specific patterns of allergic sensitization in early childhood and asthma & rhinitis risk
Authors: Stoltz D. J. , Jackson D. J. , Evans M. D. , Gangnon R. E. , Tisler C. J. , Gern J. E. , Lemanske R. F. 
Published: November 2012

SummaryBackgroundSpecific patterns of allergic sensitization as well as quantification of the in vitro IgE response in early life may provide relevant clinical insight into future rhinitis and asthma risk.ObjectiveTo define relationships among established sensitization to particular aeroallergens, quantitative analyses of allergen‐specific IgE levels, pet exposure and sensitization, and asthma and rhinitis risk.MethodsChildren at high‐risk for the development of asthma and allergic diseases were enrolled at birth into the Childhood Origins of ASThma (COAST) study. Allergen‐specific IgE was assessed at ages 1, 3, 6, and 9 years by fluoroenzyme immunoassay (Unicap® 100; Pharmacia Diagnostics). Current asthma and rhinitis were diagnosed at age 6 and 8 years.ResultsSensitization to dog was strongly associated with increased asthma risk (P < 0.0001). Sensitization to perennial compared with seasonal allergens was more strongly associated with asthma risk, while sensitization to seasonal allergens was more closely associated with rhinitis risk. Increased levels of specific IgE to perennial allergens were associated with an increased asthma risk (P = 0.05), while any detectable level of IgE to seasonal allergens was associated with increased rhinitis risk (P = 0.0009). While dog and cat sensitization were both independently associated with increased asthma and rhinitis risk, dog exposure at birth was associated with a reduced risk of asthma, regardless of dog sensitization status during the first 6 years of life (P = 0.05).Conclusions and Clinical RelevanceAnalysing specific patterns of an individual's allergic sensitization profile reveals additional relevant associations with asthma and rhinitis risk as opposed to the information gained from characterizing an individual as ‘atopic’ by the presence of any demonstrable sensitization alone. Furthermore, protective mechanisms of dog exposure with regards to asthma risk appear to be unrelated to the prevention of sensitization.
The association of cerebral palsy with birth asphyxia: a definitional quagmire
Authors: ELLENBERG JONAS H , NELSON KARIN B 
Published: November 2012

Aim  The aim of this study was to investigate whether current literature provides a useful body of evidence reflecting the proportion of cerebral palsy (CP) that is attributable to birth asphyxia.Method  We identified 23 studies conducted between 1986 and 2010 that provided data on intrapartum risks of CP.Results  The proportion of CP with birth asphyxia as a precursor (case exposure rate) varied from less than 3% to over 50% in the 23 studies reviewed. The studies were heterogeneous in many regards, including the definitions for birth asphyxia and the outcome of CP.Interpretations  Current data do not support the belief, widely held in the medical and legal communities, that birth asphyxia can be recognized reliably and specifically, or that much of CP is due to birth asphyxia. The very high case exposure rates linking birth asphyxia to CP can probably be attributed to several factors: the fact that the clinical picture at birth cannot specifically identify birth asphyxia; the definition of CP employed; and confusion of proximal effects – results – with causes. Further research is needed.
NMR structure and dynamics of the C‐terminal domain of R‐type lectin from the earthworm Lumbricus terrestris
Authors: Hemmi Hikaru , Kuno Atsushi , Hirabayashi Jun 
Published: November 2012

The C‐terminal domain (Ch; C‐half) of the R‐type earthworm 29‐kDa lectin (EW29), isolated from the earthworm Lumbricus terrestris, has two sugar‐binding sites, in subdomains α and γ, and the protein uses the two sugar‐binding sites for its function as a single domain‐type haemagglutinin. Our previous NMR titration experiments showed that the α sugar‐binding site is a high‐affinity site and the γ sugar‐binding site is a low‐affinity site. However, it remains unclear why the α sugar‐binding site of EW29Ch binds to lactose much more strongly because the crystal structure of lactose‐bound EW29Ch showed that the interaction between the α sugar‐binding site and lactose was almost same as that between the γ sugar‐binding site and lactose. In the present study, we have determined the NMR structure of EW29Ch in the sugar‐free state and performed 15N relaxation experiments for EW29Ch in both the sugar‐free state and the lactose‐bound states. The conformation of EW29Ch in the sugar‐free state was similar to that of EW29Ch in complex with lactose. Conformational changes upon binding of lactose were observed only for the α sugar‐binding site. By contrast, the 15N relaxation experiments revealed a conformational exchange at the α sugar‐binding site in the sugar‐free state, which was suppressed in the lactose‐bound state. The conformational exchange phenomenon observed for the α sugar‐binding site was not observed for the γ sugar‐binding site. Differences in the conformational change and the backbone dynamics between subdomains α and γ may be associated with the difference of the sugar‐binding modes between the two sugar‐binding sites.DatabaseStructural data for the NMR structure of EW29Ch in the sugar‐free state have been deposited in the Protein Data Bank database under accession number 2RST.