bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-inflammatory and neuroprotective effects of an orally active apocynin derivative in pre-clinical models of Parkinson’s disease
Authors: Ghosh Anamitra , Kanthasamy Arthi , Joseph Joy , Anantharam Vellareddy , Srivastava Pallavi , Dranka Brian P , Kalyanaraman Balaraman , Kanthasamy Anumantha G 
Published: October 2012

Abstract

Background
Parkinson’s disease (PD) is a devastating neurodegenerative disorder characterized by progressive motor debilitation, which affects several million people worldwide. Recent evidence suggests that glial cell activation and its inflammatory response may contribute to the progressive degeneration of dopaminergic neurons in PD. Currently, there are no neuroprotective agents available that can effectively slow the disease progression. Herein, we evaluated the anti-inflammatory and antioxidant efficacy of diapocynin, an oxidative metabolite of the naturally occurring agent apocynin, in a pre-clinical 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD.

Methods
Both pre-treatment and post-treatment of diapocynin were tested in the MPTP mouse model of PD. Diapocynin was administered via oral gavage to MPTP-treated mice. Following the treatment, behavioral, neurochemical and immunohistological studies were performed. Neuroinflammatory markers, such as ionized calcium binding adaptor molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), gp91phox and inducible nitric oxide synthase (iNOS), were measured in the nigrostriatal system. Nigral tyrosine hydroxylase (TH)-positive neurons as well as oxidative markers 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE) and striatal dopamine levels were quantified for assessment of the neuroprotective efficacy of diapocynin.

Results
Oral administration of diapocynin significantly attenuated MPTP-induced microglial and astroglial cell activation in the substantia nigra (SN). MPTP-induced expression of gp91phox and iNOS activation in the glial cells of SN was also completely blocked by diapocynin. Notably, diapocynin markedly inhibited MPTP-induced oxidative markers including 3-NT and 4-HNE levels in the SN. Treatment with diapocynin also significantly improved locomotor activity, restored dopamine and its metabolites, and protected dopaminergic neurons and their nerve terminals in this pre-clinical model of PD. Importantly, diapocynin administered 3 days after initiation of the disease restored the neurochemical deficits. Diapocynin also halted the disease progression in a chronic mouse model of PD.

Conclusions
Collectively, these results demonstrate that diapocynin exhibits profound neuroprotective effects in a pre-clinical animal model of PD by attenuating oxidative damage and neuroinflammatory responses. These findings may have important translational implications for treating PD patients.
Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy
Authors: Juan-Mateu Jonàs , Rodríguez Maria José , Nascimento Andrés , Jiménez-Mallebrera Cecilia , González-Quereda Lidia , Rivas Eloy , Paradas Carmen , Madruga Marcos , Sánchez-Ayaso Pedro , Jou Cristina , González-Mera Laura , Munell Francina , Roig-Quilis Manuel , Rabasa Maria , Hernández-Lain Aurelio , Díaz-Manera Jorge , Gallardo Eduard , Pascual Jordi , Verdura Edgard , Colomer Jaume , Baiget Montserrat , Olivé Montse , Gallano Pia 
Published: October 2012

Abstract

Background
Between 8% and 22% of female carriers of DMD mutations exhibit clinical symptoms of variable severity. Development of symptoms in DMD mutation carriers without chromosomal rearrangements has been attributed to skewed X-chromosome inactivation (XCI) favouring predominant expression of the DMD mutant allele. However the prognostic use of XCI analysis is controversial. We aimed to evaluate the correlation between X-chromosome inactivation and development of clinical symptoms in a series of symptomatic female carriers of dystrophinopathy.

Methods
We reviewed the clinical, pathological and genetic features of twenty-four symptomatic carriers covering a wide spectrum of clinical phenotypes. DMD gene analysis was performed using MLPA and whole gene sequencing in blood DNA and muscle cDNA. Blood and muscle DNA was used for X-chromosome inactivation (XCI) analysis thought the AR methylation assay in symptomatic carriers and their female relatives, asymptomatic carriers as well as non-carrier females.

Results
Symptomatic carriers exhibited 49.2% more skewed XCI profiles than asymptomatic carriers. The extent of XCI skewing in blood tended to increase in line with the severity of muscle symptoms. Skewed XCI patterns were found in at least one first-degree female relative in 78.6% of symptomatic carrier families. No mutations altering XCI in the XIST gene promoter were found.

Conclusions
Skewed XCI is in many cases familial inherited. The extent of XCI skewing is related to phenotype severity. However, the assessment of XCI by means of the AR methylation assay has a poor prognostic value, probably because the methylation status of the AR gene in muscle may not reflect in all cases the methylation status of the DMD gene.
Differential impact of body mass index and its change on the risk of breast cancer by molecular subtype: A case-control study in Japanese women
Authors: Sueta Aiko , Ito Hidemi , Islam Tania , Hosono Satoyo , Watanabe Miki , Hirose Kaoru , Fujita Takashi , Yatabe Yasushi , Iwata Hiroji , Tajima Kazuo , Tanaka Hideo , Iwase Hirotaka , Matsuo Keitaro 
Published: October 2012

Abstract
Body mass index (BMI) is an independent risk factor for luminal-type breast cancer in Western populations. However, it is unclear whether the impact of BMI differs according to breast cancer subtype in Japanese populations. We conducted a case–control study with 715 cases and 1430 age- and menopausal status-matched controls to evaluate the associations of BMI and its change (from age 20 years to the current age) with breast cancer risk. We applied conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Tumor subtypes were divided into four subtypes, namely the luminal, luminal/HER2, HER2-rich, and triple-negative subtypes. Current BMI and BMI change were positively associated with postmenopausal breast cancer risk. On stratified analysis by tumor subtype, we observed associations between current BMI and BMI change and postmenopausal breast cancer risk for the luminal subtype, with OR for each 1 kg/m2 increase in current BMI of 1.14 (95% CI: 1.07 - 1.20) and the corresponding OR of BMI change of 1.16 (1.09 - 1.23) (each P
trend
< 0.001). Additionally, we found the same tendency for the triple-negative subtype, with the OR for a 1 kg/m2 increase in current BMI of 1.21 (1.05 - 1.39) and that for BMI change of 1.18 (1.02 - 1.36) (P
trend
was 0.008 and 0.024, respectively). In premenopausal women, a suggestive inverse association was observed between BMI change and breast cancer risk for the luminal subtype only, with OR of BMI change of 0.93 (0.87 - 1.00, P
trend = 0.054). No association was seen between BMI at age 20 years and risk of any tumor subtype. In conclusion, BMI and its change are associated with the risk of both luminal and triple-negative breast cancer among postmenopausal Japanese women. These findings suggest the etiological heterogeneity of breast cancer among tumor subtypes.
Ca2+ activation of cytosolic calpain induces the transition from apoptosis to necrosis in neutrophils with externalized phosphatidylserine
Authors: Francis R J , Kotecha S , Hallett M B 
Published: October 2012

Abstract
Imaging individual aged neutrophils reveals elevated cytosolic Ca2+ in cells with externalized PS, which are vulnerable to necrosis by subsequent elevations of Ca2+.
Physiologically, apoptotic neutrophils are ingested before they undergo necrosis. However, failure of ingestion will lead to necrosis of neutrophils and the unregulated release of neutrophil-derived pathogenic molecules, such as protease and hydrolases. Understanding the mechanism of postapoptotic necrosis is thus clearly important. Here, we monitored the apoptotic-to-necrotic transition in individual-aged human neutrophils in vitro by imaging fluorescent probes for externalized PS, cytosolic Ca2+, and membrane integrity. This showed that prenecrotic-aged neutrophils with externalized PS had a significantly elevated cytosolic-free Ca2+ level. A further unregulated Ca2+ influx into PS-externalized neutrophils always preceded the necrotic transition. Ca2+ elevation was not simply a consequence of aging, as PS externalization was not uniform in similarly aged neutrophil populations. PS-externalized neutrophils could be induced to undergo necrosis experimentally by simply elevating cytosolic Ca2+ further with ionomycin. This effect was observed only in neutrophils that had externalized PS, and was independent of the time after their isolation from blood (i.e., in vitro age). As pharmacological inhibition of calpain-1 inhibition significantly reduced this CAIN, it was concluded that the apoptotic-to-necrotic transition was a consequence of uncontrolled calpain activation that resulted from Ca2+ overload in PS-externalized neutrophils.
Research Participants' High Expectations of Benefit in Early-Phase Oncology Trials: Are We Asking the Right Question?
Authors: Weinfurt Kevin P. , Seils Damon M. , Lin Li , Sulmasy Daniel P. , Astrow Alan B. , Hurwitz Herbert I. , Cohen Roger B. , Meropol Neal J. 
Published: October 2012

Purpose To determine whether patients' expectations of benefit in early-phase oncology trials depend on how patients are queried and to explore whether expectations are associated with patient characteristics. Patients and Methods Participants were 171 patients in phase I or II oncology trials in the United States. After providing informed consent for a trial but before receiving the investigational therapy, participants answered questions about expectations of benefit. We randomly assigned participants to one of three groups corresponding to three queries about expectations: frequency type, belief type, or both. Main outcomes were differences in expectations by question type and the extent to which expectations were associated with demographic characteristics, numeracy, dispositional optimism, religiousness/spirituality, understanding of research, and other measures. Results The belief-type group had a higher mean expectation of benefit (64.4 of 100) than the combination group (51.6; P = .01) and the frequency-type group (43.1; P < .001). Mean expectations in the combination and frequency groups were not significantly different (P = .06). Belief-type expectations were associated with a preference for nonquantitative information (r = −0.19; 95% CI, −0.19 to −0.36), knowledge about research (r = −0.21; 95% CI, −0.38 to −0.03), dispositional optimism (r = 0.20; 95% CI, 0.01 to 0.37), and spirituality (r = 0.22; 95% CI, 0.03 to 0.38). Frequency-type expectations were associated with knowledge about clinical research (r = −0.27; 95% CI, −0.27 to −0.51). Conclusion In early-phase oncology trials, patients' reported expectations of benefit differed according to how patients were queried and were associated with patient characteristics. These findings have implications for how informed consent is obtained and assessed.
Arterial spin labeling in patients with chronic cerebral artery steno-occlusive disease: Correlation with 15O-PET
Authors: Kamano Hironori , Yoshiura Takashi , Hiwatashi Akio , Abe Koichiro , Togao Osamu , Yamashita Koji , Honda Hiroshi 
Published: October 2012

Background Heterogeneity of arterial transit time due to cerebral artery steno-occlusive lesions hampers accurate regional cerebral blood flow measurement by arterial spin labeling (ASL). Purpose To assess the feasibility of regional cerebral blood flow measurement by ASL with multiple-delay time sampling in patients with steno-occlusive diseases by comparing with positron emission tomography (PET), and to determine whether regional arterial transit time measured by this ASL technique is correlated with regional mean transit time, a PET index of perfusion pressure. Material and Methods Sixteen patients with steno-occlusive diseases received both ASL and 15O-PET. The mean regional cerebral blood flow measured by ASL and PET, regional arterial transit time by ASL, and regional mean transit time by PET were obtained by a region-of-interest analysis. Correlation between regional cerebral blood flow by ASL and that by PET, and correlation between regional arterial transit time by ASL and regional mean transit time by PET were tested using Pearson's correlation coefficient for both absolute and relative values. A multivariate regression analysis was performed to test whether regional arterial transit time by ASL was a significant contributor in modeling regional mean transit time by PET after controlling the effect of regional cerebral blood flow by ASL. Results A significant positive correlation was found between regional cerebral blood flow by ASL and that by PET for both absolute (r = 0.520, P < 0.0001) and relative (r = 0.691, P < 0.0001) values. A significant positive correlation was found between regional arterial transit time by ASL and regional mean transit time by PET both for absolute (r = 0.369, P = 0.0002) and relative (r = 0.443, P < 0.0001) values. The regression analysis revealed that regional arterial transit time by ASL was a significant contributor in modeling regional mean transit time by PET after controlling regional cerebral blood flow by ASL (P = 0.0011). Conclusion The feasibility of regional cerebral blood flow measurement using ASL with multiple-delay time sampling was confirmed in patients with cerebral artery steno-occlusive diseases. Moreover, it was suggested that mapping of regional arterial transit time has the potential to detect hemodynamic impairment.
CT differentiation of abscess and non-infected fluid in the postoperative neck
Authors: Yoon Soo Jeong , Yoon Dae Young , Kim Sam Soo , Rho Young-Soo , Chung Eun-Jae , Eom Joong Sik , Lee Jin Seo 
Published: October 2012

BackgroundDifferentiation of postoperative neck abscess from non-infected fluid is important because the treatment is different.PurposeTo determine specific CT findings that might help to differentiate abscesses from non-infected fluid collections in the postoperative neck.Material and MethodsWe retrospectively reviewed CT scans of 50 patients (43 men and 7 women; mean age, 62.5±8.9 years) who had postoperative fluid collections in the neck (26 abscesses and 24 non-infected fluid collections). Diagnosis of an abscess was determined by a positive bacteria culture from the fluid collection. Diagnoses were correlated with the following CT findings: anatomic spaces involved, the maximum transverse diameter, margin, attenuation, rim enhancement, gas bubbles, and manifestations of soft tissue adjacent to a fluid collection.ResultsRim enhancement pattern and soft tissue manifestations showed significant differences between abscess and non-infected fluid. The reliable CT findings for abscess were: (i) rim enhancement,> 50% of the circumference, 54% sensitive, 71% specific, and 62% accurate; and (ii) severe soft tissue manifestations, 39% sensitive, 92% specific, and 64% accurate. There were no significant differences in the anatomic spaces involved, the maximum transverse diameter, margin, attenuation, and gas bubbles between abscess and non-infected fluid.ConclusionCT findings that may help differentiate postoperative neck abscess from non-infected fluid were rim enhancement > 50% of the circumference and severe soft tissue manifestations.
Evaluating the evidence: direct-to-consumer screening tests advertised online
Authors: Lovett Kimberly M , Mackey Timothy K , Liang Bryan A 
Published: October 2012

Objectives Unsupervised online direct-to-consumer (DTC) access to medical services has rapidly expanded to medical screening tests, which have not been critically evaluated for their evidence basis. The objective of this study is to identify the scope of online-advertised DTC screening tests, outline the evidence for use of available DTC testing and suggest regulatory reform to address the relevant issues. Methods An observational study of website advertisements, testing services and counselling/follow-up services for DTC testing was conducted. Data were collected from websites between 4 April and 1 June 2011. Each website was assessed for tests offered, advertised indications and availability of counselling/follow-up services. Advertised testing indications were compared with US Preventive Services Task Force recommendations and/or specialty guidelines and categorized as Supported, Against, Insufficient Evidence or No Guidance. Results Of 20 companies identified as offering DTC screening tests, 95% (19/20) do not clearly offer pretest counselling, post-test counselling and/or test follow-up. One hundred and twenty-seven different tests were identified. Only 19/127 (15%) could be Supported for screening in a target group selected for testing; 38/127 (30%) were given recommendations to avoid use in specific target group(s) selected for testing (‘ Against recommendations’); 29/127 (23%) had Insufficient Evidence of value, and for 64/127 (50%) No Guidance could be given. Only 4/127 (3%) tests were Supported for general screening use. Conclusions Virtually all identified medical tests advertised and offered DTC are not recommended for use in screening by evidence-based guidelines. Limited oversight may lead to inaccurate self-diagnosis, treatment and wasted health resources.
Three peaks in the polymerase chain reaction fragile X analysis
Authors: Sharony Reuven , Shtorch Atalia , Amiel Aliza , Guetta Esther , Peleg Leah , Pras Elon , Ries-Levavi Liat 
Published: October 2012

Objective To report and discuss the observation of three fragments on polymerase chain reaction (PCR) in routine carrier screening for fragile X. Methods From 2005 through 2010, 34,500 women underwent prenatal screening for fragile X. PCR was carried out to amplify the repeat segment. The resulting fragments were scanned by a genetic analyser. Results Three PCR peaks representing three different-sized fragments were found in 25 of the 34,500 women (1:1380 or 0.072%). Karyotype analysis was performed in 16 subjects. Full triple X was found in three women, while two had triple X mosaicism. Of the 16 karyotyped women, five (31%) had a finding of XXX (full or mosaic). Conclusions Triple X (full or mosaic) is the most frequently encountered mechanism responsible for three peaks on fragile X PCR testing.
Dramatic increase in cervical cancer registrations in young women in 2009 in England unlikely to be due to the new policy not to screen women aged 20–24
Authors: Sasieni Peter , Castanon Alejandra 
Published: October 2012

Objective To explore whether the 17% increase in cervical cancer in England in 2009 was due to the change in cervical screening policy. Methods Trends in incidence of cervical cancer and of cervical intraepithelial neoplasia grade 3 (CIN3) were analysed for England, Wales and Scotland. Invasive cervical cancer data on 4079 cancers in women aged 20–39 diagnosed between April 2007 and August 2011 in England were analysed by single year of age. Results In England there was a 38% (95% confidence intervals [CI] 18–62%) increase in cervical cancer incidence rates in women aged 25–29 in 2009 relative to 2008, and a 30% (11–51%) increase in women aged 35–39. Compared rates in 2010 are similar to those in 2008. The average increase between 2000 and 2010 in women aged 25–29 was no greater in England than in Scotland and Wales (relative risk 0.98, 95% CI 0.69–1.39). In England there has been a gradual increase in CIN3 (particularly for ages 25–29) since 2003, with a more dramatic increase in 2009, but a fall in 2010. Audit data showed an increase in cancers diagnosed at age 25 in 2009/2010 and 2010/2011 ( P ≤ 0.0004). No increase was observed at age 26. For ages 27–29 an increase in cancer was observed for 2008/2009–2009/2010 when compared with 2007/2008–2010/2011 ( P < 0.00001), but linear trends were not significant. Conclusions The increase in cervical cancer in England in 2009 cannot be attributed to the lack of screening of women aged 20–24, or to a general decrease in the coverage or quality of cervical screening.
Canada's Voluntary Sector Initiative and Sub-National Voluntary Sector-Government Relations: A Third Wave
Authors: Elson Peter R. 
Published: October 2012

AbstractFollowing a dismal and antagonistic relationship that coincided with three years of deep and sustained cuts to the voluntary sector in the mid 1990s, voluntary sector-federal government relations in Canada finally began to thaw. A number of high level joint meetings between the federal government and voluntary sector leaders in 1999 led to the announcement in June, 2000 of a joint initiative to “renew and strengthen their long-standing relationship”. This five-year $94.6 million investment entitled the Voluntary Sector Initiative (VSI) included the signing of a Voluntary Sector Accord; personnel exchange programs; policy engagement projects; two major national surveys; a national volunteerism initiative; and numerous capacity building projects.The VSI program ended in 2005 with a change in the governing Liberal party leadership and the subsequent election of a minority Conservative government. Drawing on John Kingdon’s multiple streams framework, this article takes a broad analysis of problems, policies, and political processes across multiple provinces to examine if the VSI may have influenced a third wave of sub-national level policy initiatives. While contextual differences at a provincial level clearly influence the status, structure, and scope of sub-national voluntary sector-government relations, it appears the VSI did contribute in a number of ways to these sub-national initiatives.
Ein »Parlamentsheer« ohne »preußische Erbstücke«? Die zivil-militärischen Konflikte um die Führungsorganisation der Kaiserlichen Schutztruppen
Authors: Bührer Tanja 
Published: October 2012

Zusammenfassung
Die Kaiserlichen Schutztruppen waren im Unterschied zur Preußischen Armee und zur Marine der Kaiserlichen Kommandogewalt weitgehend entzogen. Dieser Bruch mit der konservativen Militärpolitik wurde dadurch ermöglicht, dass die politischen und militärischen Eliten in der Gründungsphase der Schutzgebiete und -truppen den absoluten Primat auf die kontinentale Sicherheit legten und ein ernsthaftes Engagement der etablierten Streitkräfte an der Peripherie entschieden ablehnten. Den Führungsspitzen der Armee und der Marine missfiel es aber grundsätzlich, dass die leitenden Stellen der zivilen Kolonialbehörden militärische Kernkompetenzen ausübten. Durch die ganze Institutionsgeschichte der Schutztruppe hindurch sollten sie daher in einem Konflikt mit den Kolonialbehörden über die konstitutionelle Stellung dieser militärischen Formation stehen. Zwar blieb die zivile Kontrolle über das Militär in den Kolonien auf dem Papier erhalten, sie konnte in ausgeprägten Bedrohungslagen dem Druck der Militärs jedoch nicht standhalten. So ignorierte der Kommandeur der ostafrikanischen Schutztruppe, von Lettow-Vorbeck, alle verfassungsrechtlichen Hindernisse und übernahm die militärische Macht im Schutzgebiet. Obwohl es sich dabei letztlich um einen Militärputsch handelt, war Lettow-Vorbecks Handlungsweise zutiefst in der preußischen Militärtradition verankert und machte es möglich, dass der Kommandeur zum Kriegshelden wurde.