bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complement component 3 inhibition by an antioxidant is neuroprotective after cerebral ischemia and reperfusion in mice
Authors: Yang Jiwon , Ahn Hye‐na , Chang Minsun , Narasimhan Purnima , Chan Pak H. , Song Yun Seon 
Published: December 2012

AbstractOxidative stress after stroke is associated with the inflammatory system activation in the brain. The complement cascade, especially the degradation products of complement component 3, is a key inflammatory mediator of cerebral ischemia. We have shown that pro‐inflammatory complement component 3 is increased by oxidative stress after ischemic stroke in mice using DNA array. In this study, we investigated whether up‐regulation of complement component 3 is directly related to oxidative stress after transient focal cerebral ischemia in mice and oxygen‐glucose deprivation in brain cells. Persistent up‐regulation of complement component 3 expression was reduced in copper/zinc‐superoxide dismutase transgenic mice, and manganese‐superoxide dismutase knock‐out mice showed highly increased complement component 3 levels after transient focal cerebral ischemia. Antioxidant N‐tert‐butyl‐α‐phenylnitrone treatment suppressed complement component 3 expression after transient focal cerebral ischemia. Accumulation of complement component 3 in neurons and microglia was decreased by N‐tert‐butyl‐α‐phenylnitrone, which reduced infarct volume and impaired neurological deficiency after cerebral ischemia and reperfusion in mice. Small interfering RNA specific for complement component 3 transfection showed a significant increase in brain cells viability after oxygen‐glucose deprivation. Our study suggests that the neuroprotective effect of antioxidants through complement component 3 suppression is a new strategy for potential therapeutic approaches in stroke.
Utility of oral cancer diagnostic adjuncts in the adult US populations
Authors: Bhoopathi Vinodh , Mascarenhas Ana Karina 
Published: December 2012

BackgroundUtility of diagnostic adjuncts (DAs) in an adult population with a low oral and pharyngeal cancer (OPC) prevalence is unclear. In this study, we compare the effectiveness of DAs and clinicians' conventional oral examination (COE) in detecting oral and pharyngeal cancers (OPC), in high‐risk (HR) users, low‐risk (LR) and alcohol, and in the overall adult US populations (GP).MethodsWe assumed oral cancer DAs to have 99% sensitivity and specificity. For COE, 79.6% sensitivity and 97.7% specificity were used. Using Altman's mathematical model, the positive predictive values (PPV) for a DA and COE were estimated for HR, LR, and GP groups, respectively. Three different scenarios (sensitivity constant but decreasing specificity, specificity constant but decreasing sensitivity, and decreasing both sensitivity and specificity simultaneously) were developed to simulate the true effectiveness of DAs while keeping the prevalence of OPC in HR, LR, and GP groups constant at 0.4039%, 0.0362%, and 0.1109%, respectively.ResultsThe PPVs for a DA in HR, LR, and GP groups in the United States were estimated at 29%, 3%, and 10%, while for COE, the PPVs would be at 12%, 1%, and 4%, respectively.ConclusionsUtility of DAs in LR and GP groups is negligible due to very low OPC prevalence in these populations. In HR population, DAs may have a slightly better effectiveness than clinicians only when assumed to have high sensitivity and specificity.
Divergent Effects of Aging and Sex on Vasoconstriction to Endothelin in Coronary Arterioles
Authors: LeBlanc Amanda J. , Chen Bei , Dougherty Patrick J. , Reyes Rafael A. , Shipley Robert D. , Korzick Donna H. , Muller‐Delp Judy M. 
Published: December 2012

AbstractObjectiveThe risk for cardiovascular disease increases with advancing age; however, the chronological development of heart disease differs in males and females. The purpose of this study was to determine whether age‐induced alterations in responses of coronary arterioles to the endogenous vasoconstrictor, endothelin, are sex‐specific.MethodsCoronary arterioles were isolated from young and old male and female rats to assess vasoconstrictor responses to endothelin (ET), and ETa and ETb receptor inhibitors were used to assess receptor‐specific signaling.ResultsIn intact arterioles from males, ET‐induced vasoconstriction was reduced with age, whereas age increased vasoconstrictor responses to ET in intact arterioles from female rats. In intact arterioles from both sexes, blockade of either ETa or ETb eliminated age‐related differences in responses to ET; however, denudation of arterioles from both sexes revealed age‐related differences in ETa‐mediated vasoconstriction. In arterioles from male rats, ETa receptor protein decreased, whereas ETb receptor protein increased with age. In coronary arterioles from females, neither ETa nor ETb receptor protein changed with age, suggesting age‐related changes in ET signaling occur downstream of ET receptors.ConclusionsThus, aging‐induced alterations in responsiveness of the coronary resistance vasculature to endothelin are sex‐specific, possibly contributing to sexual dimorphism in the risk of cardiovascular disease with advancing age.
Corneal changes following near work in myopic anisometropia
Authors: Vincent Stephen J , Collins Michael J , Read Scott A , Carney Leo G , Yap Maurice KH 
Published: December 2012

AbstractPurposeTo examine the symmetry of corneal changes following near work in the fellow eyes of non‐amblyopic myopic anisometropes.MethodsThirty‐four non‐amblyopic, myopic anisometropes (minimum 1 D spherical equivalent anisometropia) had corneal topography measured before and after a controlled near work task. Subjects were positioned in a headrest to minimise head movements and read continuous text on a computer monitor for 10 min at an angle of 25 degrees downward gaze and an accommodation demand of 2.5 D. Measures of the morphology of the palpebral aperture during primary and downward gaze were also obtained.ResultsThe more and less myopic eyes exhibited a high degree of interocular symmetry for measures of palpebral aperture morphology during both primary and downward gaze. Following the near work task, fellow eyes also displayed a symmetrical change in superior corneal topography (hyperopic defocus) which correlated with the position of the upper eyelid during downward gaze. Greater changes in the spherical corneal power vector (M) following reading were associated with a narrower palpebral aperture during downward gaze (p = 0.07 for more myopic and p = 0.03 for less myopic eyes). A significantly greater change in J0 (an increase in against the rule astigmatism) was observed in the more myopic eyes (−0.04 ± 0.04 D) compared to the less myopic eyes (−0.02 ± 0.06 D) over a 6 mm corneal diameter (p = 0.01).ConclusionsChanges in corneal topography following near work are highly symmetrical between the fellow eyes of myopic anisometropes due to the interocular symmetry of the palpebral aperture. However, the more myopic eye exhibits changes in corneal astigmatism of greater magnitude compared to the less myopic eye.
IL‐1β and IL‐6 activate inflammatory responses of astrocytes against Naegleria fowleri infection via the modulation of MAPKs and AP‐1
Authors: Kim J.‐H. , Song A.‐R. , Sohn H.‐J. , Lee J. , Yoo J.‐K. , Kwon D. , Shin H.‐J. 
Published: December 2012

SummaryNaegleria fowleri, a free‐living amoeba, has been found in diverse habitats throughout the world. It causes primary amoebic meningoencephalitis in children and young adults. The amoeba attaches to nasal mucosa, migrates along olfactory nerves and enters the brain. Astrocytes are involved in the defence against infection and produce inflammatory responses. In this study, we focus on the mechanism of immune responses in astrocytes. We showed, using RNase protection assay, RT‐PCR and ELISA in an in vitro culture system, that N. fowleri lysates induce interleukin‐1beta (IL‐1β) and IL‐6 expression of astrocytes. In addition, cytokine levels of astrocytes gradually decreased due to extracellular signal‐regulated kinase (ERK), c‐Jun N‐terminal kinase (JNK) and p38 inhibitors. To determine the transcription factor, we used transcription inhibitor (AP‐1 inhibitor), which downregulated IL‐1β and IL‐6 expression. These results show that AP‐1 is related to IL‐1β and IL‐6 production. N. fowleri‐mediated IL‐1β and IL‐6 expression requires ERK, JNK and p38 mitogen‐activated protein kinases (MAPKs) activation in astrocytes. These findings show that N. fowleri‐stimulated astrocytes in an in vitro culture system lead to AP‐1 activation and the subsequent expressions of IL‐1β and IL‐6, which are dependent on ERK, JNK and p38 MAPKs activation. These results may imply that proinflammatory cytokines have important roles in inflammatory responses to N. fowleri infection.
N‐glycan maturation is crucial for cytokinin‐mediated development and cellulose synthesis in Oryza sativa
Authors: Fanata Wahyu Indra Duwi , Lee Kyoung Hwan , Son Bo Hwa , Yoo Jae Yong , Harmoko Rikno , Ko Ki Seong , Ramasamy Nirmal Kumar , Kim Kyung Hwa , Oh Doo‐Byoung , Jung Hyun Suk , Kim Jae‐Yean , Lee Sang Yeol , Lee Kyun Oh 
Published: December 2012

SummaryTo explore the physiological significance of N‐glycan maturation in the plant Golgi apparatus, gnt1, a mutant with loss of N‐acetylglucosaminyltransferase I (GnTI) function, was isolated in Oryza sativa. gnt1 exhibited complete inhibition of N‐glycan maturation and accumulated high‐mannose N‐glycans. Phenotypic analyses revealed that gnt1 shows defective post‐seedling development and incomplete cell wall biosynthesis, leading to symptoms such as failure in tiller formation, brittle leaves, reduced cell wall thickness, and decreased cellulose content. The developmental defects of gnt1 ultimately resulted in early lethality without transition to the reproductive stage. However, callus induced from gnt1 seeds could be maintained for periods, although it exhibited a low proliferation rate, small size, and hypersensitivity to salt stress. Shoot regeneration and dark‐induced leaf senescence assays indicated that the loss of GnTI function results in reduced sensitivity to cytokinin in rice. Reduced expression of A‐type O. sativa response regulators that are rapidly induced by cytokinins in gnt1 confirmed that cytokinin signaling is impaired in the mutant. These results strongly support the proposed involvement of N‐glycan maturation in transport as well as in the function of membrane proteins that are synthesized via the endomembrane system.
Elevated energy coupling and aerobic capacity improves exercise performance in endurance‐trained elderly subjects
Authors: Conley Kevin E. , Jubrias Sharon A. , Cress M. Elaine , Esselman Peter C. 
Published: December 2012

New Findings
What is the central question of this study?Does exercise performance reflect the improvements in mitochondrial capacity and energy coupling efficiency found with endurance training in elderly subjects?
What is the main finding and its importance?Exercise performance of the elderly benefits from elevations in energy coupling and oxidative phosphorylation capacity at both the whole‐body and muscle levels that accompany endurance training.
Increased maximal oxygen uptake (), mitochondrial capacity and energy coupling efficiency are reported after endurance training (ET) in adult subjects. Here we test whether leg exercise performance (power output of the legs, Pmax, at ) reflects these improvements with ET in the elderly. Fifteen male and female subjects were endurance trained for a 6 month programme, with 13 subjects (69.5 ± 1.2 years old, range 65–80 years old; n= 7 males; n= 6 females) completing the study. This training significantly improved Pmax (Δ17%; P= 0.003), (Δ5.4%; P= 0.021) and the increment in oxygen uptake () above resting (; Δ9%; P < 0.02). In addition, evidence of improved energy coupling came from elevated leg power output per unit at the aerobic capacity [Δ(Pmax/); P= 0.02] and during submaximal exercise in the ramp test as measured by delta efficiency (ΔPex/Δ; P= 0.04). No change was found in blood lactate, muscle glycolysis or fibre type. The rise in Pmax paralleled the improvement in muscle oxidative phosphorylation capacity (ATPmax) in these subjects. In addition, the greater exercise energy coupling [Δ(Pmax/) and delta efficiency] was accompanied by increased mitochondrial energy coupling as measured by elevated ATP production per unit mitochondrial content in these subjects. These results suggest that leg exercise performance benefits from elevations in energy coupling and oxidative phosphorylation capacity at both the whole‐body and muscle levels that accompany endurance training in the elderly.
Patients’ silence towards the healthcare system after ethical transgressions by staff: associations with patient characteristics in a cross-sectional study among Swedish female patients
Authors: Brüggemann A Jelmer , Swahnberg Katarina 
Published: December 2012

ObjectivesTo identify which patient characteristics are associated with silence towards the healthcare system after experiences of abusive or ethically wrongful transgressive behaviour by healthcare staff.DesignCross-sectional questionnaire study using the Transgressions of Ethical Principles in Health Care Questionnaire.SettingA women's clinic in the south of Sweden.ParticipantsSelection criteria were: consecutive female patients coming for an outpatient appointment, ≥18-year-old, with the ability to speak and understand the Swedish language, and a known address.Questionnaires were answered by 534 women (60%) who had visited the clinic, of which 293 were included in the present study sample.Primary outcome measureHow many times the respondent remained silent towards the healthcare system relative to the number of times the respondent spoke up.ResultsAssociations were found between patients’ silence towards the healthcare system and young age as well as lower self-rated knowledge of patient rights. Both variables showed independent effects on patients’ silence in a multivariate model. No associations were found with social status, country of birth, health or other abuse.ConclusionsThe results offer opportunities for designing interventions to stimulate patients to speak up and open up the clinical climate, for which the responsibility lies in the hands of staff; but more research is needed.
Validity of theInternational Classification of Diseases, Tenth Revisioncode for acute kidney injury in elderly patients at presentation to the emergency department and at hospital admission
Authors: Hwang Y Joseph , Shariff Salimah Z , Gandhi Sonja , Wald Ron , Clark Edward , Fleet Jamie L , Garg Amit X 
Published: December 2012

ObjectiveTo evaluate the validity of theInternational Classification of Diseases, Tenth Revision(ICD-10) code N17x for acute kidney injury (AKI) in elderly patients in two settings: at presentation to the emergency department and at hospital admission.DesignA population-based retrospective validation study.SettingSouthwestern Ontario, Canada, from 2003 to 2010.ParticipantsElderly patients with serum creatinine measurements at presentation to the emergency department (n=36 049) or hospital admission (n=38 566). The baseline serum creatinine measurement was a median of 102 and 39 days prior to presentation to the emergency department and hospital admission, respectively.Main outcome measuresSensitivity, specificity and positive and negative predictive values of ICD-10 diagnostic coding algorithms for AKI using a reference standard based on changes in serum creatinine from the baseline value. Median changes in serum creatinine of patients who were code positive and code negative for AKI.ResultsThe sensitivity of the best-performing coding algorithm for AKI (defined as a ≥2-fold increase in serum creatinine concentration) was 37.4% (95% CI 32.1% to 43.1%) at presentation to the emergency department and 61.6% (95% CI 57.5% to 65.5%) at hospital admission. The specificity was greater than 95% in both settings. In patients who were code positive for AKI, the median (IQR) increase in serum creatinine from the baseline was 133 (62 to 288) µmol/l at presentation to the emergency department and 98 (43 to 200) µmol/l at hospital admission. In those who were code negative, the increase in serum creatinine was 2 (−8 to 14) and 6 (−4 to 20) µmol/l, respectively.ConclusionsThe presence or absence of ICD-10 code N17× differentiates two groups of patients with distinct changes in serum creatinine at the time of a hospital encounter. However, the code underestimates the true incidence of AKI due to a limited sensitivity.
A case report of evaluating a large-scale health systems improvement project in an uncontrolled setting: a quality improvement initiative in KwaZulu-Natal, South Africa
Authors: Mate Kedar S , Ngidi Wilbroda Hlolisile , Reddy Jennifer , Mphatswe Wendy , Rollins Nigel , Barker Pierre 
Published: December 2012

ObjectiveNew approaches are needed to evaluate quality improvement (QI) within large-scale public health efforts. This case report details challenges to large-scale QI evaluation, and proposes solutions relying on adaptive study design.Study designWe used two sequential evaluative methods to study a QI effort to improve delivery of HIV preventive care in public health facilities in three districts in KwaZulu-Natal, South Africa, over a 3-year period. We initially used a cluster randomised controlled trial (RCT) design.Principal findingsDuring the RCT study period, tensions arose between intervention implementation and evaluation design due to loss of integrity of the randomisation unit over time, pressure to implement changes across the randomisation unit boundaries, and use of administrative rather than functional structures for the randomisation. In response to this loss of design integrity, we switched to a more flexible intervention design and a mixed-methods quasiexperimental evaluation relying on both a qualitative analysis and an interrupted time series quantitative analysis.ConclusionsCluster RCT designs may not be optimal for evaluating complex interventions to improve implementation in uncontrolled ‘real world’ settings. More flexible, context-sensitive evaluation designs offer a better balance of the need to adjust the intervention during the evaluation to meet implementation challenges while providing the data required to evaluate effectiveness. Our case study involved HIV care in a resource-limited setting, but these issues likely apply to complex improvement interventions in other settings.
Urethral caruncle: a lesion related to IgG4-associated sclerosing disease?
Authors: Williamson Sean R , Scarpelli Marina , Lopez-Beltran Antonio , Montironi Rodolfo , Conces Miriam R , Cheng Liang 
Published: December 2012

AimsUrethral caruncle is a benign, polypoid urethral mass that occurs almost exclusively in postmenopausal women. Despite that these lesions are routinely managed with topical medications or excision, their pathogenesis is not well understood. We investigated the possibilities of autoimmune, viral and inflammatory myofibroblastic proliferations as possible aetiologies.MethodsIn 38 patients with urethral caruncle, we utilised immunohistochemistry for immunoglobulin G (IgG) and IgG4 to assess for a potential autoimmune aetiology. Immunohistochemistry was performed in nine patients for Epstein–Barr virus, BK virus, human herpesvirus 8, human papillomavirus, adenovirus and anaplastic lymphoma kinase.ResultsFour patients (11%) showed infiltrates of ≥50 IgG4-positive plasma cells per high power field, of which all showed an IgG4 to IgG ratio greater than 40%. A statistically significant difference (p<0.01) was detected in the mean number of IgG4-positive cells (14.73 per high power field) compared with control benign urethral specimens (mean, 1.19). One patient with increased counts below this threshold had rheumatoid arthritis; none had documented autoimmune pancreatitis or other known manifestations of systemic IgG4-related sclerosing disease. All lesions showed negative reactions for the viral and inflammatory myofibroblastic markers.ConclusionsUrethral caruncle is a benign inflammatory and fibrous polypoid urethral mass of unclear aetiology. It appears unrelated to viral infection and lacks the abnormal expression of anaplastic lymphoma kinase protein, as seen in inflammatory myofibroblastic tumours. Increased numbers of IgG4-positive plasma cells in a subset of lesions raise the possibility that some cases may be related to the autoimmune phenomena of IgG4-associated disease.
The changing contribution of smoking to educational differences in life expectancy: indirect estimates for Finnish men and women from 1971 to 2010
Authors: Martikainen Pekka , Ho Jessica Y , Preston Samuel , Elo Irma T 
Published: December 2012

BackgroundWe estimated the contribution of smoking to educational differences in mortality and life expectancy between 1971 and 2010 in Finland.MethodsEight prospective datasets with baseline in 1970, 1975, 1980, 1985, 1990, 1995, 2000 and 2005 and each linked to a 5-year mortality follow-up were used. We calculated life expectancy at age 50 years with and without smoking-attributable mortality by education and gender. Estimates of smoking-attributable mortality were based on an indirect method that used lung cancer mortality as a proxy for the impact of smoking on mortality from all other causes.ResultsSmoking-attributable deaths constituted about 27% of all male deaths above age 50 years in the early 1970s and 17% in the period 2006–2010; these figures were 1% and 4% among women, respectively. The life expectancy differential between men with basic versus high education increased from 3.4 to 4.7 years between 1971–1975 and 2006–2010. In the absence of smoking, these differences would have been 1.5 and 3.4 years, 1.9 years (55%) and 1.3 years (29%) less than those observed. Among women, educational differentials in life expectancy between the most and least educated increased from 2.5 to 3.0 years. This widening was nearly entirely accounted for by the increasing impact of smoking. Among women the contribution of smoking to educational differences had increased from being negligible in 1971–1975 to 16% in 2006–2010.ConclusionsAmong men, the increase in educational differences in mortality in the past decades was driven by factors other than smoking. However, smoking continues to have a major influence on educational differences in mortality among men and its contribution is increasing among women.