bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysautonomia after pediatric brain injury
Authors: KIRK KATHERINE A , SHOYKHET MICHAEL , JEONG JONG H , TYLER‐KABARA ELIZABETH C , HENDERSON MARYANNE J , BELL MICHAEL J , FINK ERICKA L 
Published: June 2012

Aim  Dysautonomia after brain injury is a diagnosis based on fever, tachypnea, hypertension, tachycardia, diaphoresis, and/or dystonia. It occurs in 8 to 33% of adults with brain injury and is associated with poor outcome. We hypothesized that children with brain injury with dysautonomia have worse outcomes and prolonged rehabilitation, and sought to determine the prevalence of dysautonomia in children and to characterize its clinical features.Method  We developed a database of children (n=249, 154 males, 95 females; mean [SD] age 11 years 10 months [5y 7mo]) with traumatic brain injury, cardiac arrest, stroke, infection of the central nervous system, or brain neoplasm admitted for rehabilitation to The Children’s Institute of Pittsburgh between 2002 and 2009. Dysautonomia diagnosis, injury type, clinical signs, length of stay, and Functional Independence Measure for Children (WeeFIM) testing were extracted from medical records, and analysed for differences between groups with and without dysautonomia.Results  Dysautonomia occurred in 13% of children with brain injury (95% confidence interval 9.3–18.0%), occurring in 10% after traumatic brain injury and 31% after cardiac arrest. The combination of hypertension, diaphoresis, and dystonia best predicted a diagnosis of dysautonomia (area under the curve=0.92). Children with dysautonomia had longer stays, worse WeeFIM scores, and improved less on the score’s motor component (all p≤0.001).Interpretation  Dysautonomia is common in children with brain injury and is associated with prolonged rehabilitation. Prospective study and standardized diagnostic approaches are needed to maximize outcomes.
Inhibition of lysosome degradation on autophagosome formation and responses to GMI, an immunomodulatory protein from Ganoderma microsporum
Authors: Hsin I‐Lun , Sheu Gwo‐Tarng , Jan Ming‐Shiou , Sun Hai‐Lun , Wu Tzu‐Chin , Chiu Ling‐Yen , Lue Ko‐Huang , Ko Jiunn‐Liang 
Published: June 2012

BACKGROUND AND PURPOSE Autophagic cell death is considered a self‐destructive process that results from large amounts of autophagic flux. In our previous study, GMI, a recombinant fungal immunomodulatory protein cloned from Ganoderma microsporum, induced autophagic cell death in lung cancer cells. The aim of this study was to examine the role of autophagosome accumulation in GMI‐mediated cell death.EXPERIMENTAL APPROACH Western blot analysis, flow cytometry and confocal microscopy were used to evaluate the effects of different treatments, including silencing of ATP6V0A1 by use of short hairpin RNAi, on GMI‐mediated cell death, lung cancer cell viability and autophagosome accumulation in vitro.KEY RESULTS Lysosome inhibitors bafilomycin‐A1 and chloroquine increased GMI‐mediated autophagic cell death. GMI and bafilomycin‐A1 co‐treatment induced the accumulation of large amounts of autophagosomes, but did not significantly induce apoptosis. GMI elicited autophagy through the PKB (Akt)/mammalian target of rapamycin signalling pathway. Silencing of ATP6V0A1, one subunit of vesicular H+‐ATPases (V‐ATPases) that mediates lysosome acidification, spontaneously induced autophagosome accumulation, but did not affect lysosome acidity. GMI‐mediated autophagosome accumulation and cytotoxicity was increased in shATP6V0A1 lung cancer cells. Furthermore, ATP6V0A1 silencing decreased autophagosome and lysosome fusion in GMI‐treated CaLu‐1/GFP‐LC3 lung cancer cells.CONCLUSION AND IMPLICATIONS We demonstrated that autophagosome accumulation induces autophagic cell death in a GMI treatment model, and ATP6V0A1 plays an important role in mediating autophagosome‐lysosome fusion. Our findings provide new insights into the mechanisms involved in the induction of autophagic cell death.
Axial Diffusivity and Tensor Shape as Early Markers to Assess Cerebral White Matter Damage Caused by Brain Tumors Using Quantitative Diffusion Tensor Tractography
Authors: Chen Fei , Zhang Xin , Li Ming , Wang Rong , Wang Hui‐Ting , Zhu Feng , Lu De‐Ji , Zhao Hui , Li Jing‐Wei , Xu Yun , Zhu Bin , Zhang Bing 
Published: June 2012

SummaryAimsWe investigated the usefulness of diffusion tensor tractography (DTT) for differentiating between histological pathologies and evaluating white matter (WM) damage resulting from brain tumors. We also sought to categorize the appearance of brain tumor–related WM tract changes.MethodsA total of 18 inpatients with intracranial neoplasms were enrolled. MRI examinations were performed at 3 T using an 8‐channel phased array coil. DTT was reconstruction from the raw data of diffusion tensor imaging. WM tract–based analysis of the mean diffusivity (MD), eigenvalues (λ1, λ2, λ3), and fractional anisotropy (FA) was performed by the manual placement of regions of interest (ROIs) on the color‐coded FA maps using DTIStudio software. The axial diffusivity (DA, namely λ1) and the tensor shape (Cl, namely (λ1 − λ2)/3 (λ)) were also compared between groups. P values <0.05 were considered statistically significant.ResultsIn cases of low‐grade glioma (LGG), the tracts adjacent to the tumors displayed the highest levels of invasion. Tract disruption was mainly observed in cases of high‐grade glioma (HGG). We found significant differences regarding the FA, MD, DA, and radial diffusivity between ROIs in patients with LGG or HGG. There were also significant differences in DA and tensor shape (Cl) between patients with LGG and HGG.ConclusionAxial diffusivity and Cl may be useful early markers for differentiating between LGG and HGG.
Pattern of skin thickness progression and clinical correlation in Thai scleroderma patients
Authors: Foocharoen Chingching , Mahakkanukrauh Ajanee , Suwannaroj Siraphop , Nanagara Ratanavadee 
Published: June 2012

AbstractBackgroundSkin thickness progression in scleroderma (SSc) varies in daily clinical practice observation.ObjectivesTo define the pattern of skin thickness among Thai sufferers of SSc and to ascertain the clinical correlation with each skin pattern.MethodsA 3‐year follow‐up cohort was performed on patients over 15 years of age in Khon Kaen, Thailand, between January 1, 2005 and December 31, 2006. The progression of skin thickness equals the modified Rodnan skin score at the end minus the score at onset divided by the duration of the disease.Results
SSc cases (117) were included and the female‐to‐male ratio was 70 : 47. The mean age at onset was 49.8 years (range 24.4–75.5). The most common skin patterns were: (i) ‘slow progression to peak then slow regression’ (77 cases; 65.8%); followed by (ii) ‘continuous slow progression’ (37; 31.6%); (iii) ‘continuous intermediate progression’ (2; 1.7%); and (iv) ‘slow progression to peak then intermediate regression’ (1; 0.9%). The respective mean peak skin score and duration of disease at peak skin score was 19.8 points (range 4–45) and 20.3 months (range 1.0–42.2). Only telangiectasia at onset and contracture of joint(s) were related to ‘continuous slow progression’ of skin thickness with P = 0.001 and P = 0.042, respectively. Neither SSc subsets nor internal organ involvement were correlated with skin thickness pattern.ConclusionThe most common skin pattern in Thai SSc was ‘slow progression to peak then slow regression’. Telangiectasia at onset and contracture of joint(s) were predictive of continuous progressive skin thickness in the first 3 years.
Socioeconomic variation in diet and activity‐related behaviours of Australian children and adolescents aged 2–16 years
Authors: Cameron A. J. , Ball K. , Pearson N. , Lioret S. , Crawford D. A. , Campbell K. , Hesketh K. , McNaughton S. A. 
Published: June 2012

SummaryBackgroundEvidence for age‐related variation in the relationship between obesity‐related behaviours and socioeconomic position may assist in the targeting of dietary and physical activity interventions among children.ObjectiveTo investigate the relationship between different indicators of socioeconomic position and obesity‐related behaviours across childhood and adolescence.MethodsData were from 4487 children aged 2 to 16 years participating in the cross‐sectional 2007 Australian National Children's Nutrition and Physical Activity Survey. Socioeconomic position was defined by the highest education of the primary or secondary carer and parental income. Activity was assessed using recall methods with physical activity also assessed using pedometers. Intake of energy‐dense drinks and snack foods, fruits and vegetables was assessed using 2 × 24‐h dietary recalls.ResultsA socioeconomic gradient was evident for each dietary measure (although in age‐specific analyses, not for energy‐dense snacks in older children), as well as television viewing, but not physical activity. Whether each behaviour was most strongly related to parental income or education of the primary or secondary carer was age and sex dependent. The socioeconomic gradient was strongest for television viewing time and consumption of fruit and energy‐dense drinks.ConclusionsA strong socioeconomic gradient in eating behaviours and television viewing time was observed. Relationships for particular behaviours differed by age, sex and how socioeconomic position was defined. Socioeconomic indicators define different population groups and represent different components of socioeconomic position. These findings may provide insights into who should be targeted in preventive health efforts at different life stages.
Differential changes in vascular mRNA levels between rat iliac and renal arteries produced by cessation of voluntary running
Authors: Padilla Jaume , Jenkins Nathan T. , Roberts Michael D. , Arce‐Esquivel Arturo A. , Martin Jeffrey S. , Laughlin M. Harold , Booth Frank W. 
Published: June 2012

New Findings
What is the central question of this study?While it is well accepted that long‐term physical inactivity is associated with an increased cardiovascular risk, the early effects of adoption of a sedentary lifestyle on the vasculature have not been characterized at the molecular level.
What is the main finding and its importance?The primary finding of this study is that transition from high to low physical activity produces modest changes in mRNA expression for some pro‐and anti‐atherogenic genes, but that both the genes affected and direction of change differ between iliac and renal artery. This heterogeneous effect of short‐term physical inactivity could be attributed to the distinct alterations in haemodynamic forces between these arteries.
Early vascular changes at the molecular level caused by adoption of a sedentary lifestyle are incompletely characterized. Herein, we employed the rodent wheel‐lock model to identify mRNAs in the arterial wall that are responsive to the acute transition from higher to lower levels of daily physical activity. Specifically, we evaluated whether short‐term cessation of voluntary wheel running alters vascular mRNA levels in rat conduit arteries previously reported to have marked increases (i.e. iliac artery) versus marked decreases (i.e. renal artery) in blood flow during running. We used young female Wistar rats with free access to voluntary running wheels. Following 23 days of voluntary running (average distance of ∼15 km per night; ∼4.4 h per night), rats in one group were rapidly transitioned to a sedentary state by locking the wheels for 7 days (n= 9; wheel‐lock 7 day rats) or remained active in a second group for an additional 7 days (n= 9; wheel‐lock 0 day rats). Real‐time PCR was conducted on total RNA isolated from iliac and renal arteries to evaluate expression of 25 pro‐atherogenic and anti‐atherogenic genes. Compared with the iliac arteries of wheel‐lock 0 day rats, iliac arteries of wheel‐lock 7 day rats exhibited increased expression of TNFR1 (+19%), ET1 (+59%) and LOX‐1 (+31%; all P < 0.05). Moreover, compared with renal arteries of wheel‐lock 0 day rats, renal arteries of wheel‐lock 7 day rats exhibited decreased expression of ETb (−23%), p47phox (−32%) and p67phox (−19%; all P < 0.05). These data demonstrate that cessation of voluntary wheel running for 7 days produces modest, but differential changes in mRNA levels between the iliac and renal arteries of healthy rats. This heterogeneous influence of short‐term physical inactivity could be attributed to the distinct alteration in haemodynamic forces between arteries.
Effect of Linezolid on the 50% Lethal Dose and 50% Protective Dose in Treatment of Infections by Gram-Negative Pathogens in Naive and Immunosuppressed Mice and on the Efficacy of Ciprofloxacin in an Acute Murine Model of Septicemia
Authors: Marra Andrea , Lamb Lucinda , Medina Ivette , George David , Gibson Glenn , Hardink Joel , Rugg Jady , Van Deusen Jeffrey , O'Donnell John P. 
Published: June 2012

ABSTRACTMurine models of infection were used to study the effect of linezolid on the virulence of Gram-negative bacteria and to assess potential pharmacodynamic interactions with ciprofloxacin in the treatment of these infections, prompted by observations from a recent clinical trial. Naive and immunosuppressed mice were challenged withKlebsiella pneumoniae53A1109,K. pneumoniaeGC6658, andPseudomonas aeruginosaUC12120 in acute sepsis and pulmonary infection models, using different serial dilutions of these pathogens (groups of 8 animals each). Linezolid (100 mg/kg/dose) was administered orally at 0.5 and 4.0 h postchallenge in the sepsis model and at 4 h postchallenge followed by 2 days of twice-daily treatment in the pulmonary model. Further, ciprofloxacin alone and in combination with oral linezolid was investigated in the sepsis model. Survival was assessed for 4 and 10 days postchallenge in the systemic and respiratory models, respectively. The data were fitted to a nonlinear regression analysis to determine 50% lethal doses (LD50s) and 50% protective doses (PD50s). A clinically relevant, high-dose regimen of linezolid had no significant effect on LD50in these models. This lack of effect was independent of immune status. A combination of oral ciprofloxacin with linezolid yielded lower PD50s than oral ciprofloxacin alone (ciprofloxacin in combination, 8.4 to 32.7 mg/kg; oral ciprofloxacin, 39.4 to 88.3 mg/kg). Linezolid did not improve the efficacy of subcutaneous ciprofloxacin (ciprofloxacin in combination, 2.0 to 2.4 mg/kg; subcutaneous ciprofloxacin, 2.0 to 2.8 mg/kg). In conclusion, linezolid does not seem to potentiate infections caused by Gram-negative pathogens or to interact antagonistically with ciprofloxacin.
Staphylococcus aureus VRSA-11B Is a Constitutive Vancomycin-Resistant Mutant of Vancomycin-Dependent VRSA-11A
Authors: Périchon Bruno , Courvalin Patrice 
Published: June 2012

ABSTRACT

Vancomycin-resistant
Staphylococcus aureus
VRSA-10 was isolated in 2009, whereas VRSA-11A and VRSA-11B were isolated from the same patient in 2010. Growth curves and determination of the nature of the peptidoglycan precursors and of the VanX
d,d
-dipeptidase activity in the absence and in the presence of vancomycin indicated that vancomycin resistance was inducible in VRSA-10, that VRSA-11A was partially dependent on glycopeptide for growth, and that VRSA-11B was constitutively resistant. Both VRSA-11A and -11B harbored an insertion sequence, IS
Ef1
, at the same locus in the
vanX-vanY
intergenic region of Tn
1546
and an S
183
A mutation in the chromosomal
d
-alanyl:
d
-alanine ligase (Ddl). This substitution has been shown to be responsible for a drastic diminution of the affinity of the enzyme for
d
-Ala at subsite 1 in
Escherichia coli
DdlB. VRSA-11B exhibited an additional mutation, P
216
T, in the transcriptional regulator VanR, most probably associated with constitutive expression of vancomycin resistance. It is thus likely that VRSA-11B is a constitutive derivative of VRSA-11A selected during prolonged vancomycin therapy. Synthesis of peptidoglycan precursors ending in
d
-Ala-
d
-lactate was responsible for oxacillin susceptibility of VRSA-11A and VRSA-11B despite the presence of a wild-type
mecA
gene in both strains.
Distinct Transcriptional Programs Mediated by the Ligand-Dependent Full-Length Androgen Receptor and Its Splice Variants in Castration-Resistant Prostate Cancer
Authors: Hu Rong , Lu Changxue , Mostaghel Elahe A. , Yegnasubramanian Srinivasan , Gurel Meltem , Tannahill Clare , Edwards Joanne , Isaacs William B. , Nelson Peter S. , Bluemn Eric , Plymate Stephen R. , Luo Jun 
Published: June 2012

Abstract
Continued androgen receptor (AR) signaling is an established mechanism underlying castration-resistant prostate cancer (CRPC), and suppression of androgen receptor signaling remains a therapeutic goal of CRPC therapy. Constitutively active androgen receptor splice variants (AR-Vs) lack the androgen receptor ligand-binding domain (AR-LBD), the intended target of androgen deprivation therapies including CRPC therapies such as abiraterone and MDV3100. While the canonical full-length androgen receptor (AR-FL) and AR-Vs are both increased in CRPCs, their expression regulation, associated transcriptional programs, and functional relationships have not been dissected. In this study, we show that suppression of ligand-mediated AR-FL signaling by targeting AR-LBD leads to increased AR-V expression in two cell line models of CRPCs. Importantly, treatment-induced AR-Vs activated a distinct expression signature enriched for cell-cycle genes without requiring the presence of AR-FL. Conversely, activation of AR-FL signaling suppressed the AR-Vs signature and activated expression programs mainly associated with macromolecular synthesis, metabolism, and differentiation. In prostate cancer cells and CRPC xenografts treated with MDV3100 or abiraterone, increased expression of two constitutively active AR-Vs, AR-V7 and ARV567ES, but not AR-FL, paralleled increased expression of the androgen receptor–driven cell-cycle gene UBE2C. Expression of AR-V7, but not AR-FL, was positively correlated with UBE2C in clinical CRPC specimens. Together, our findings support an adaptive shift toward AR-V–mediated signaling in a subset of CRPC tumors as the AR-LBD is rendered inactive, suggesting an important mechanism contributing to drug resistance to CRPC therapy. Cancer Res; 72(14); 3457–62. ©2012 AACR.
Influence of Polymorphic OATP1B-Type Carriers on the Disposition of Docetaxel
Authors: de Graan Anne-Joy M. , Lancaster Cynthia S. , Obaidat Amanda , Hagenbuch Bruno , Elens Laure , Friberg Lena E. , de Bruijn Peter , Hu Shuiying , Gibson Alice A. , Bruun Gitte H. , Corydon Thomas J. , Mikkelsen Torben S. , Walker Aisha L. , Du Guoqing , Loos Walter J. , van Schaik Ron H. N. , Baker Sharyn D. , Mathijssen Ron H. J. , Sparreboom Alex 
Published: June 2012

Abstract
Purpose: Docetaxel is extensively metabolized by CYP3A4 in the liver but mechanisms by which the drug is taken up into hepatocytes remain poorly understood. We hypothesized that (i) liver uptake of docetaxel is mediated by the polymorphic solute carriers OATP1B1 and OATP1B3 and (ii) inherited genetic defects in this process may impair systemic drug elimination.
Experimental Design: Transport of docetaxel was studied in vitro using various cell lines stably transfected with OATP1B1*1A (wild-type), OATP1B1*5 [c.521T&gt;C (V174A); rs4149056], OATP1B3, or the mouse transporter Oatp1b2. Docetaxel clearance was evaluated in wild-type and Oatp1b2-knockout mice as well as in two cohorts of patients with multiple variant transporter genotypes (n = 213).
Results: Docetaxel was found to be a substrate for OATP1B1, OATP1B3, and Oatp1b2 but was not transported by OATP1B1*5. Deficiency of Oatp1b2 in mice was associated with an 18-fold decrease in docetaxel clearance (P = 0.0099), which was unrelated to changes in intrinsic metabolic capacity in mouse liver microsomes. In patients, however, none of the studied common reduced function variants in OATP1B1 or OATP1B3 were associated with docetaxel clearance (P &gt; 0.05).
Conclusions: The existence of at least two potentially redundant uptake transporters in the human liver with similar affinity for docetaxel supports the possibility that functional defects in both of these proteins may be required to confer substantially altered disposition phenotypes. In view of the established exposure–toxicity relationships for docetaxel, we suggest that caution is warranted if docetaxel has to be administered together with agents that potently inhibit both OATP1B1 and OATP1B3. Clin Cancer Res; 18(16); 4433–40. ©2012 AACR.
Trans,trans,trans-[PtIV(N3)2(OH)2(py)(NH3)]: A Light-Activated Antitumor Platinum Complex That Kills Human Cancer Cells by an Apoptosis-Independent Mechanism
Authors: Westendorf Aron F. , Woods Julie A. , Korpis Katharina , Farrer Nicola J. , Salassa Luca , Robinson Kim , Appleyard Virginia , Murray Karen , Grünert Renate , Thompson Alastair M. , Sadler Peter J. , Bednarski Patrick J. 
Published: June 2012

AbstractPhotoactivatable PtIV diazido complexes have unusual photobiologic properties. We show here that trans,trans,trans-[PtIV(N3)2(OH)2(py)(NH3)] complex 3 is a potent photoactivated cytotoxin toward human cancer cells in culture, with an average IC50 value in 13 cell lines of 55 ± 28 μmol/L after 30 minutes (0.12 mW/cm2) photoactivation with UVA, although visible light was also effective. Photoactivated complex 3 was noncross-resistant to cisplatin in 3 of 4 resistant cell lines. Cell swelling but very little blebbing was seen for HL60 cells treated with irradiated complex 3. Unlike cisplatin and etoposide, both of which cause apoptosis in HL60 cells, no apoptosis was observed for UVA-activated complex 3 by the Annexin V/propidium iodide flow cytotometry assay. Changes in the levels of the autophagic proteins LC3B-II and p62 in HL60 cells treated with UVA-activated complex 3 indicate autophagy is active during cell death. In a clonogenic assay with the SISO human cervix cancer cell line, 3 inhibited colony formation when activated by UVA irradiation. Antitumor activity of complex 3 in mice bearing xenografted OE19 esophageal carcinoma tumors was photoaugmented by visible light. Insights into the novel reaction pathways of complex 3 have been obtained from 14N{1H} nuclear magnetic resonance studies, which show that photoactivation pathways can involve release of free azide in buffered solution. Density functional theory (DFT) and time-dependent DFT calculations revealed the dissociative character of singlet and triplet excited states of complex 3, which gives rise to reactive, possibly cytotoxic azidyl radicals. Mol Cancer Ther; 11(9); 1894–904. ©2012 AACR.
Jyotiprasad Agarwala: A Revolutionary Cultural Architect of Twentieth Century Assam
Authors: Dutta Akhil Ranjan 
Published: June 2012

Jyotiprasad is one of the leading cultural architects of twentieth century Assam. The life span of Jyotiprasad Agarwala (1903–51) corresponds to a historical phase of transition of Assamese and Indian society to a modern era. This phase was marked both by achievements and setbacks. The freedom movement got enriched during this phase and attained intensity through different experiments and achieved the most desired independence amid the tragedies of partition and communal cleansing. This was also a period when both the Assamese and the rest of India attained the consciousness of modern self-entity in all aspects of art, literature, science and culture. In Assam, too, which was the hinterland of colonialism, the creative and vibrant consciousness of the new age awakened the general masses. Jyotiprasad was a true representative of this age of cultural awakening of the Assamese society. The present article is an attempt to explore the revolutionary cultural philosophy of Jyotiprasad Agarwala and its relevance for social transformation.