bluuebunny/crossref_metadata_2025 huggingface dataset:
But Where Were They? Race, Era(c)sure, and the Imaginary American West
Authors: Callier Durell M.
Published: August 2012

Deeply embedded within the myth of the settlement of the American frontier is a systematically conscious project of era(c)sure. This imperial project necessitates and indeed perpetuates a cultural amnesia, disappearing the lives, stories, and histories of not only native and indigenous people but that of all other racial and ethnically marginalized peoples. Through a series of autoethnographic confessions interspersed with historic/academic texts, nursery rhymes, and minstrel song lyrics But Where Were They offers a personal wrestling with the complex consequences of the era(c)sure of race in nostalgia of Americas western frontier.
Complicated Cerebral Venous Sinus Thrombosis With Intracranial Hemorrhage and Mastoiditis
Authors: Skeik Nedaa , Stark Madeline M. , Tubman David E.
Published: August 2012

Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke, occurring when a blood clot forms in any of the brain venous sinuses. Symptoms include neurological deficits, headache, seizures, and coma. There are many predisposing factors for CVST including prothrombotic conditions, oral contraceptives, pregnancy/puerperium, malignancy, infection, and head injury. Cerebral venous sinus thrombosis has no identifiable underlying etiology in about 12.5% to 33% of the cases. Diagnosis has become easier with newer imaging techniques, such as magnetic resonance venography. The treatment options for CVST include symptomatic treatment, anticoagulation (AC), thrombolysis, and thrombectomy. Controversy exists over the efficacy and safety of AC in patients with CVST with concurrent intracranial hemorrhage (ICH). We present a complex case of CVST with ICH and mastoiditis as well as provide a literature review about CVST.
Potential explanations for control group benefit
Authors: Nichols Linda O , Martindale-Adams Jennifer L , Burns Robert , Graney Marshall J , Zuber Jeffrey K , Kennedy Sarah E
Published: August 2012

Background

Estimating effectiveness of clinical interventions depends on detecting differences between the responses of intervention and control groups. The outcome, intervention, and moderating factors all may influence the between group change. The absence of a clinically or statistically meaningful difference may also result from control group improvement due to nonspecific factors such as participants’ perception of attention, positive regard, expectations, desire to please, and therapeutic alliance with the care provider.

Purpose

We examined perceived benefit and sources of benefit for control caregivers who participated in the CONNECT randomized controlled trial of a dementia caregiving intervention.

Methods

After the final scheduled data collection in CONNECT, control group participants were asked whether they believed they benefited from study participation. Those who reported benefit were asked to describe the benefit received. Data were analyzed qualitatively.

Results

Of 60 available control caregivers, 82% reported a perceived benefit from study participation in five areas: getting information about dementia and caregiving; having someone to talk to and feeling supported; receiving understanding and validation of feelings; knowledge that others were in similar situations; and perceived appreciation of own abilities. Control caregivers who reported benefit were less burdened and depressed and spent less time on duty at baseline than those who did not report benefit. From caregivers’ responses, we have identified the assessment battery, both content and time spent in data collection, as a possible mechanism of action for benefit.

Limitations

Study limitations include the better baseline characteristics of the control caregivers who reported benefit, the sample size of benefit control caregivers, the possibility of perceptions of benefit being a function of social desirability, and the lack of a similar question about benefit being asked of intervention caregivers.

Conclusions

These findings suggest that the outcome assessment questionnaires used in this and similar trials may be an intervention of sorts for caregiver participants in the control group. Caregivers who are less distressed may benefit more from the attention provided during assessment. These findings underscore the importance of asking caregivers how they are doing. For researchers, there is a need to develop innovative ways to assess outcomes to avoid unintended benefit of assessments.
Recommendations of the National Football League Physician Society Task Force on the Use of Toradol® Ketorolac in the National Football League
Authors: Matava Matthew , Brater D. Craig , Gritter Nancy , Heyer Robert , Rollins Douglas , Schlegel Theodore , Toto Robert , Yates Anthony
Published: August 2012

Ketorolac tromethamine (Toradol®) is a non-steroidal anti-inflammatory drug that has potent analgesic and anti-inflammatory properties. It can be administered orally, intravenously, intramuscularly, or via a nasal route. Ketorolac injections have been used for several years in the National Football League (NFL), in both the oral and injectable forms, to treat musculoskeletal injuries and to prevent post-game soreness. In an attempt to determine the appropriate use of this medication in NFL players, the NFL Team Physician Society appointed a Task Force to consider the best available evidence as to how ketorolac should be used for pain management in professional football players. These treatment recommendations were established based on the available medical literature taking into consideration the pharmacokinetic properties of ketorolac, its accepted indications and contraindications, and the unique clinical challenges of the NFL. The Task Force recommended that 1) ketorolac should only be administered under the direct supervision and order of a team physician; 2) ketorolac should not be used prophylactically as a means of reducing anticipated pain either during or after participation in NFL games or practices and should be limited to those players diagnosed with an injury or condition and listed on the teams’ injury report; 3) ketorolac should be given in the lowest effective therapeutic dose and should not be used in any form for more than 5 days; 4) ketorolac should be given in its oral preparation under typical circumstances; 5) ketorolac should not be taken concurrently with other NSAIDs or by those players with a history of allergic reaction to ketorolac, other NSAIDs or aspirin; and 6) ketorolac should not be used by a player with a history of significant gastrointestinal bleeding, renal compromise, or a past history of complications related to NSAIDs.
“The Missing Link”
Authors: Spates Kamesha
Published: August 2012

Critical examinations of epistemology argue that White men have established the guidelines for scientific knowledge. Because other groups were never allotted the opportunity to contribute to the immense knowledge base, the Western scientific knowledge base remains deficient. The author calls for a more inclusive knowledge base that includes the voices of Black women in the field of psychology. This inclusion is critical to better equip mental health clinicians to handle the unique needs of this population. This article offers a historical analysis of the intricate relationship between race and scientific knowledge. The author examines how the close-knit relationship between race and science has directly influenced the existing scientific knowledge gaps surrounding Black women in the field of psychology and calls for literature to offer a more comprehensive view of Black women’s experiences.
Expression of the runt homology domain of RUNX1 disrupts homeostasis of hematopoietic stem cells and induces progression to myelodysplastic syndrome
Authors: Matsuura Shinobu , Komeno Yukiko , Stevenson Kristen E. , Biggs Joseph R. , Lam Kentson , Tang Tingdong , Lo Miao-Chia , Cong Xiuli , Yan Ming , Neuberg Donna S. , Zhang Dong-Er
Published: August 2012

Mutations of RUNX1 are detected in patients with myelodysplastic syndrome (MDS). In particular, C-terminal truncation mutations lack a transcription regulatory domain and have increased DNA binding through the runt homology domain. The expression of the runt homology domain, RUNX1(41-214), in mouse hematopoietic cells induced progression to MDS and acute myeloid leukemia. Analysis of premyelodysplastic animals found expansion of c-Kit+Sca-1+Lin− cells and skewed differentiation to myeloid at the expense of the lymphoid lineage. These abnormalities correlate with the phenotype of Runx1-deficient animals, as expected given the reported dominant-negative role of C-terminal mutations over the full-length RUNX1. However, MDS is not observed in Runx1-deficient animals. Gene expression profiling found that RUNX1(41-214) c-Kit+Sca-1+Lin− cells have an overlapping yet distinct gene expression profile from Runx1-deficient animals. Moreover, an unexpected parallel was observed between the hematopoietic phenotype of RUNX1(41-214) and aged animals. Genes deregulated in RUNX1(41-214), but not in Runx1-deficient animals, were inversely correlated with the aging gene signature of HSCs, suggesting that disruption of the expression of genes related to normal aging by RUNX1 mutations contributes to development of MDS. The data presented here provide insights into the mechanisms of development of MDS in HSCs by C-terminal mutations of RUNX1.
SRSF2 mutations in 275 cases with chronic myelomonocytic leukemia (CMML)
Authors: Meggendorfer Manja , Roller Andreas , Haferlach Torsten , Eder Christiane , Dicker Frank , Grossmann Vera , Kohlmann Alexander , Alpermann Tamara , Yoshida Kenichi , Ogawa Seishi , Koeffler H. Phillip , Kern Wolfgang , Haferlach Claudia , Schnittger Susanne
Published: August 2012

We analyzed the mutational hotspot region of SRSF2 (Pro95) in 275 cases with chronic myelomonocytic leukemia (CMML). In addition, ASXL1, CBL, EZH2, JAK2V617F, KRAS, NRAS, RUNX1, and TET2 mutations were investigated in subcohorts. Mutations in SRSF2 (SRSF2mut) were detected in 47% (129 of 275) of all cases. In detail, 120 cases had a missense mutation at Pro95, leading to a change to Pro95His, Pro95Leu, Pro95Arg, Pro95Ala, or Pro95Thr. In 9 cases, 3 new in/del mutations were observed: 7 cases with a 24-bp deletion, 1 case with a 3-bp duplication, and 1 case with a 24-bp duplication. In silico analyses predicted a damaging character for the protein structure of SRSF2 for all mutations. SRSF2mut was correlated with higher age, less pronounced anemia, and normal karyotype. SRSF2mut and EZH2mut were mutually exclusive, but SRSF2mut was associated with TET2mut. In the total cohort, no effect of SRSF2mut on survival was observed. However, in the RUNX1mut subcohort, SRSF2 Pro95His had a favorable effect on overall survival. This comprehensive mutation analysis found that 93% of all patients with CMML carried at least 1 somatic mutation in 9 recurrently mutated genes. In conclusion, these data show the importance of SRSF2mut as new diagnostic marker in CMML.
The efficacy and the risk of immunogenicity of FIX Padua (R338L) in hemophilia B dogs treated by AAV muscle gene therapy
Authors: Finn Jonathan D. , Nichols Timothy C. , Svoronos Nikolaos , Merricks Elizabeth P. , Bellenger Dwight A. , Zhou Shangshen , Simioni Paolo , High Katherine A. , Arruda Valder R.
Published: August 2012

Studies on gene therapy for hemophilia B (HB) using adeno-associated viral (AAV) vectors showed that the safety of a given strategy is directly related to the vector dose. To overcome this limitation, we sought to test the efficacy and the risk of immunogenicity of a novel factor IX (FIX) R338L associated with ∼ 8-fold increased specific activity. Muscle-directed expression of canine FIX-R338L by AAV vectors was carried out in HB dogs. Therapeutic levels of circulating canine FIX activity (3.5%-8%) showed 8- to 9-fold increased specific activity, similar to humans with FIX-R338L. Phenotypic improvement was documented by the lack of bleeding episodes for a cumulative 5-year observation. No antibody formation and T-cell responses to FIX-R338L were observed, even on challenges with FIX wild-type protein. Moreover, no adverse vascular thrombotic complications were noted. Thus, FIX-R338L provides an attractive strategy to safely enhance the efficacy of gene therapy for HB.
Two glutamic acid residues in the DNA-binding domain are engaged in the release of STAT1 dimers from DNA
Authors: Koch Verena , Staab Julia , Ruppert Volker , Meyer Thomas
Published: August 2012

Background

In interferon-γ-stimulated cells, the dimeric transcription factor STAT1 (s ignal t ransducer and a ctivator of t ranscription 1) recognizes semi-palindromic motifs in the promoter regions of cytokine-driven target genes termed GAS (g amma-a ctivated s ites). However, the molecular steps that facilitate GAS binding and the subsequent liberation of STAT1 homodimers from these promoter elements are not well understood.

Results

Using a mutational approach, we identified two critical glutamyl residues within the DNA-binding domain adjacent to the phosphodiester backbone of DNA which efficiently release phospho-STAT1 from DNA. The release of STAT1 dimers from DNA enhances transcriptional activity on both interferon-driven reporter and endogenous target genes. A substitution of either of the two glutamic acid residues broadens the repertoire of putative binding sites on DNA and enhances binding affinity to GAS sites. However, despite elevated levels of tyrosine phosphorylation and a prolonged nuclear accumulation period, the STAT1 DNA-binding mutants show a significantly reduced transcriptional activity upon stimulation of cells with interferon-γ. This reduced transcriptional response may be explained by the deposition of oligomerized STAT1 molecules outside GAS sites.

Conclusions

Thus, two negatively charged amino acid residues in the DNA-binding domain are engaged in the liberation of STAT1 from DNA, resulting in a high dissociation rate from non-GAS sites as a key feature of STAT1 signal transduction, which positively regulates cytokine-dependent gene expression probably by preventing retention at transcriptionally inert sites.
Identification of miRNAs and their targets from Brassica napus by high-throughput sequencing and degradome analysis
Authors: Xu Miao Y , Dong Yun , Zhang Qiu X , Zhang Lan , Luo Yan Z , Sun Jie , Fan Yun L , Wang Lei
Published: August 2012

Background

MicroRNAs (miRNAs) are endogenous regulators of a broad range of physiological processes and act by either degrading mRNA or blocking its translation. Oilseed rape (Brassica napus) is one of the most important crops in China, Europe and other Asian countries with publicly available expressed sequence tags (ESTs) and genomic survey sequence (GSS) databases, but little is known about its miRNAs and their targets. To date, only 46 miRNAs have been identified in B. napus.

Results

Forty-one conserved and 62 brassica-specific candidate B. napus miRNAs, including 20 miRNA* sequences, were identified using Solexa sequencing technology. Furthermore, 33 non-redundant mRNA targets of conserved brassica miRNAs and 19 new non-redundant mRNA targets of novel brassica-specific miRNAs were identified by genome-scale sequencing of mRNA degradome.

Conclusions

This study describes large scale cloning and characterization of B. napus miRNAs and their potential targets, providing the foundation for further characterization of miRNA function in the regulation of diverse physiological processes in B. napus.
Narrow band quantitative and multivariate electroencephalogram analysis of peri-adolescent period
Authors: Rodríguez Martinez EI , Barriga-Paulino CI , Zapata MI , Chinchilla C , López-Jiménez AM , Gómez CM
Published: August 2012

Background

The peri-adolescent period is a crucial developmental moment of transition from childhood to emergent adulthood. The present report analyses the differences in Power Spectrum (PS) of the Electroencephalogram (EEG) between late childhood (24 children between 8 and 13 years old) and young adulthood (24 young adults between 18 and 23 years old).

Results

The narrow band analysis of the Electroencephalogram was computed in the frequency range of 0–20 Hz. The analysis of mean and variance suggested that six frequency ranges presented a different rate of maturation at these ages, namely: low delta, delta-theta, low alpha, high alpha, low beta and high beta. For most of these bands the maturation seems to occur later in anterior sites than posterior sites. Correlational analysis showed a lower pattern of correlation between different frequencies in children than in young adults, suggesting a certain asynchrony in the maturation of different rhythms. The topographical analysis revealed similar topographies of the different rhythms in children and young adults. Principal Component Analysis (PCA) demonstrated the same internal structure for the Electroencephalogram of both age groups. Principal Component Analysis allowed to separate four subcomponents in the alpha range. All these subcomponents peaked at a lower frequency in children than in young adults.

Conclusions

The present approaches complement and solve some of the incertitudes when the classical brain broad rhythm analysis is applied. Children have a higher absolute power than young adults for frequency ranges between 0-20 Hz, the correlation of Power Spectrum (PS) with age and the variance age comparison showed that there are six ranges of frequencies that can distinguish the level of EEG maturation in children and adults. The establishment of maturational order of different frequencies and its possible maturational interdependence would require a complete series including all the different ages.
The effect of sulindac, a non-steroidal anti-inflammatory drug, attenuates inflammation and fibrosis in a mouse model of chronic pancreatitis
Authors: Bai Han , Chen Xiaokai , Zhang Lin , Dou Xiaoguang
Published: August 2012

Background

Chronic pancreatitis is characterized by progressive fibrosis, pain and loss of exocrine and endocrine functions. The long-standing chronic pancreatitis and its associated pancreatic fibrosis are the most common pathogenic events involved in human pancreatic carcinogenesis, but the therapeutic strategies to chronic pancreatitis and the chemoprevention of pancreatic carcinogenesis are very limited.

Methods

We investigated the effect of sulindac, a non-steroidal anti-inflammatory drug (NSAID), on inhibition of chronic pancreatitis in a caerulein induced chronic pancreatitis mouse model.

Results

Sulindac significantly reduced the severity of chronic pancreatitis including the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The protein expression of phosphorylation of MEK/ERK was inhibited in the chronic pancreatic tissues by sulindac treatment as measured by Western blot assay. The levels of inflammatory cytokines including TNF-α and MCP-1 were also significantly decreased with sulindac treatment, as well as the expression of TGF-β, PDGF-β, SHH and Gli in the chronic pancreatic tissue detected by qPCR assay and confirmed by western blot assay. The activation of pancreatic satellet cells was also inhibited by sulindac as measured by the activity of α-smooth muscle actin (α-SMA) in the pancreatic tissue of chronic pancreatitis.

Conclusions

Sulindac is a promising reagent for the treatment of chronic pancreatitis via inhibition of inflammatory cell infiltration and stromal fibrosis, the inhibitory effect of sulindac on chronic pancreatitis may through targeting the activation ERK/MAPK signaling pathway.
Effect of add-on direct renin inhibitor aliskiren in patients with non-diabetes related chronic kidney disease
Authors: Li Szu-yuan , Chen Yung-Tai , Yang Wu-Chang , Tarng Der-Cherng , Lin Chih-Ching , Yang Chih-Yu , Liu Wen-Sheng
Published: August 2012

Background

The renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of chronic kidney disease (CKD). Although dual RAAS inhibition results in worse renal outcomes than monotherapy in high risk type 2 diabetes patients, the effect of dual RAAS inhibition in patients with non-DM CKD is unclear. The aim of this study was to evaluate the potential renoprotective effect of add-on direct renin inhibitor in non-DM CKD patients.

Methods

We retrospectively enrolled 189 non-DM CKD patients who had been taking angiotensin II receptor blockers (ARBs) for more than six months. Patients were divided into an add-on aliskiren group and an ARB monotherapy group. The primary outcomes were a decline in glomerular filtration rate (GFR) and a reduction in urinary protein-to-creatinine ratio at six months.

Results

The baseline characteristics of the two groups were similar. Aliskiren 150 mg daily reduced the urinary protein-to-creatinine ratio by 26% (95% confidence interval, 15 to 37%; p < 0.001). The decline in GFR was smaller in the add-on aliskiren group (−2.1 vs. -4.0 ml/min, p = 0.038). Add-on aliskiren had a neutral effect on serum potassium in the non-DM CKD patients. In subgroup analysis, the proteinuria-reducing effect of aliskiren was more prominent in patients with a GFR less than 60 ml/min, and in patients with a urinary protein-to-creatinine ratio greater than 1.8. The effect of aliskiren in retarding the decline in GFR was more prominent in patients with hypertensive nephropathy than in those with glomerulonephritis.

Conclusion

Add-on direct renin inhibitor aliskiren (150 mg daily) safely reduced proteinuria and attenuated the decline in GFR in the non-DM CKD patients who were receiving ARBs.
Characterization of genetic rearrangements in esophageal squamous carcinoma cell lines by a combination of M-FISH and array-CGH: further confirmation of some split genomic regions in primary tumors
Authors: Hao Jia-Jie , Shi Zhi-Zhou , Zhao Zhi-Xin , Zhang Yu , Gong Ting , Li Chun-Xiang , Zhan Ting , Cai Yan , Dong Jin-Tang , Fu Song-Bin , Zhan Qi-Min , Wang Ming-Rong
Published: August 2012

Background

Chromosomal and genomic aberrations are common features of human cancers. However, chromosomal numerical and structural aberrations, breakpoints and disrupted genes have yet to be identified in esophageal squamous cell carcinoma (ESCC).

Methods

Using multiplex-fluorescence in situ hybridization (M-FISH) and oligo array-based comparative hybridization (array-CGH), we identified aberrations and breakpoints in six ESCC cell lines. Furthermore, we detected recurrent breakpoints in primary tumors by dual-color FISH.

Results

M-FISH and array-CGH results revealed complex numerical and structural aberrations. Frequent gains occurred at 3q26.33-qter, 5p14.1-p11, 7pter-p12.3, 8q24.13-q24.21, 9q31.1-qter, 11p13-p11, 11q11-q13.4, 17q23.3-qter, 18pter-p11, 19 and 20q13.32-qter. Losses were frequent at 18q21.1-qter. Breakpoints that clustered within 1 or 2 Mb were identified, including 9p21.3, 11q13.3-q13.4, 15q25.3 and 3q28. By dual-color FISH, we observed that several recurrent breakpoint regions in cell lines were also present in ESCC tumors. In particular, breakpoints clustered at 11q13.3-q13.4 were identified in 43.3% (58/134) of ESCC tumors. Both 11q13.3-q13.4 splitting and amplification were significantly correlated with lymph node metastasis (LNM) (P = 0.004 and 0.022) and advanced stages (P = 0.004 and 0.039). Multivariate logistic regression analysis revealed that only 11q13.3-q13.4 splitting was an independent predictor for LNM (P = 0.026).

Conclusions

The combination of M-FISH and array-CGH helps produce more accurate karyotypes. Our data provide significant, detailed information for appropriate uses of these ESCC cell lines for cytogenetic and molecular biological studies. The aberrations and breakpoints detected in both the cell lines and primary tumors will contribute to identify affected genes involved in the development and progression of ESCC.
Antimicrobial and antioxidant activities of the extracts and compounds from the leaves of Psorospermum aurantiacum Engl. and Hypericum lanceolatum Lam.
Authors: Tchakam Patricia D , Lunga Paul K , Kowa Théodora K , Lonfouo Antoine Honoré N , Wabo Hippolyte K , Tapondjou Léon A , Tane Pierre , Kuiate Jules-Roger
Published: August 2012

Background

Psorospermun aurantiacum and Hypericum lanceolatum are plants locally used in Cameroon and other parts of Africa for the treatment of gastrointestinal and urinary tract infections, skin infections, venereal diseases, gastrointestinal disorder, infertility, epilepsy as well as microbial infections. The present study was designed in order to investigate the in vitro antimicrobial and radical scavenging activities of the extracts and isolated compounds from the leaves of these plants.

Methods

The plant extract was prepared by maceration in ethyl acetate and methanol and fractionated by column chromatography. The structures of isolated compounds were elucidated by spectroscopic analyses in conjunction with literature data. The broth microdilution method was used to evaluate the in vitro antimicrobial activity against bacteria, yeasts and dermatophytes. The antioxidant potentials of the extracts and their isolated compounds were evaluated using the DPPH radical scavenging method.

Results

Five known compounds: physcion (1), 1,8-dihydroxy-3-geranyloxy-6-methylanthraquinone (2), kenganthranol B (3), vismiaquinone (4), and octacosanol (5) were isolated from the leaves of P. aurantiacum while six compounds including friedelin (6), betulinic acid (7), 2,2’,5,6’-tetrahydroxybenzophenone (8), allanxanthone A (9), 1,3,6- trihydroxyxanthone (10) and isogarcinol (11) were isolated from H. lanceolatum. Compound 8 and 4 exhibited the highest antibacterial and antifungal activities with MIC ranges of 2–8 μg/ml and 4–32 μg/ml respectively. P. aurantiacum crude extract (Rsa50 = 6.359 ± 0.101) showed greater radical scavenging activity compared with H. lanceolatum extract (Rsa50 = 30.996 ± 0.879). Compound 11 showed the highest radical scavenging activity (RSa50 = 1.012 ± 0.247) among the isolated compounds, comparable to that of L-arscobic acid (RSa50 = 0.0809 ± 0.045).

Conclusions

The experimental findings show that the ethyl acetate and methanol extracts and isolated compounds from P. aurantiacum and H. lanceolatum stem bark possess significant antimicrobial and antioxidant activities justifying the use of these plants in traditional medicine, which may be developed as phytomedicines.
Identification and location of hot and cold spots of treated prevalence of depression in Catalonia (Spain)
Authors: Salinas-Pérez José A , García-Alonso Carlos R , Molina-Parrilla Cristina , Jordà-Sampietro Esther , Salvador-Carulla Luis
Published: August 2012

Background

Spatial analysis is a relevant set of tools for studying the geographical distribution of diseases, although its methods and techniques for analysis may yield very different results. A new hybrid approach has been applied to the spatial analysis of treated prevalence of depression in Catalonia (Spain) according to the following descriptive hypotheses: 1) spatial clusters of treated prevalence of depression (hot and cold spots) exist and, 2) these clusters are related to the administrative divisions of mental health care (catchment areas) in this region.

Methods

In this ecological study, morbidity data per municipality have been extracted from the regional outpatient mental health database (CMBD-SMA) for the year 2009. The second level of analysis mapped small mental health catchment areas or groups of municipalities covered by a single mental health community centre. Spatial analysis has been performed using a Multi-Objective Evolutionary Algorithm (MOEA) which identified geographical clusters (hot spots and cold spots) of depression through the optimization of its treated prevalence. Catchment areas, where hot and cold spots are located, have been described by four domains: urbanicity, availability, accessibility and adequacy of provision of mental health care.

Results

MOEA has identified 6 hot spots and 4 cold spots of depression in Catalonia. Our results show a clear spatial pattern where one cold spot contributed to define the exact location, shape and borders of three hot spots. Analysing the corresponding domain values for the identified hot and cold spots no common pattern has been detected.

Conclusions

MOEA has effectively identified hot/cold spots of depression in Catalonia. However these hot/cold spots comprised municipalities from different catchment areas and we could not relate them to the administrative distribution of mental care in the region. By combining the analysis of hot/cold spots, a better statistical and operational-based visual representation of the geographical distribution is obtained. This technology may be incorporated into Decision Support Systems to enhance local evidence-informed policy in health system research.
Sugarcane bagasse pretreatment using three imidazolium-based ionic liquids; mass balances and enzyme kinetics
Authors: Karatzos Sergios Kimon , Edye Leslie Alan , Doherty William Orlando Sinclair
Published: August 2012

Background

Effective pretreatment is key to achieving high enzymatic saccharification efficiency in processing lignocellulosic biomass to fermentable sugars, biofuels and value-added products. Ionic liquids (ILs), still relatively new class of solvents, are attractive for biomass pretreatment because some demonstrate the rare ability to dissolve all components of lignocellulosic biomass including highly ordered (crystalline) cellulose. In the present study, three ILs, 1-butyl-3-methylimidazolium chloride ([C4mim]Cl), 1-ethyl-3-methylimidazolium chloride ([C2mim]Cl), 1-ethyl-3-methylimidazolium acetate ([C2mim]OAc) are used to dissolve/pretreat and fractionate sugarcane bagasse. In these IL-based pretreatments the biomass is completely or partially dissolved in ILs at temperatures greater than 130°C and then precipitated by the addition of an antisolvent to the IL biomass mixture. For the first time mass balances of IL-based pretreatments are reported. Such mass balances, along with kinetics data, can be used in process modelling and design.

Results

Lignin removals of 10% mass of lignin in bagasse with [C4mim]Cl, 50% mass with [C2mim]Cl and 60% mass with [C2mim]OAc, are achieved by limiting the amount of water added as antisolvent to 0.5 water:IL mass ratio thus minimising lignin precipitation. Enzyme saccharification (24 h, 15FPU) yields (% cellulose mass in starting bagasse) from the recovered solids rank as: [C2mim]OAc(83%) > >[C2mim]Cl(53%) = [C4mim]Cl(53%). Composition of [C2mim]OAc-treated solids such as low lignin, low acetyl group content and preservation of arabinosyl groups are characteristic of aqueous alkali pretreatments while those of chloride IL-treated solids resemble aqueous acid pretreatments. All ILs are fully recovered after use (100% mass as determined by ion chromatography).

Conclusions

In all three ILs regulated addition of water as an antisolvent effected a polysaccharide enriched precipitate since some of the lignin remained dissolved in the aqueous IL solution. Of the three IL studied [C2mim]OAc gave the best saccharification yield, material recovery and delignification. The effects of [C2mim]OAc pretreatment resemble those of aqueous alkali pretreatments while those of [C2mim]Cl and [C4mim]Cl resemble aqueous acid pretreatments. The use of imidazolium IL solvents with shorter alkyl chains results in accelerated dissolution, pretreatment and degradation.
In vitro glucocorticoid sensitivity is associated with clinical glucocorticoid therapy outcome in rheumatoid arthritis
Authors: Quax Rogier AM , Koper Jan W , de Jong Pascal HP , van Heerebeek Ramona , Weel Angelique E , Huisman Anne M , van Zeben Derkjen , de Jong Frank H , Lamberts Steven WJ , Hazes Johanna MW , Feelders Richard A
Published: August 2012

Introduction

Genetic and disease-related factors give rise to a wide spectrum of glucocorticoid (GC) sensitivity in rheumatoid arthritis (RA). In clinical practice, GC treatment is not adapted to these differences in GC sensitivity. In vitro assessment of GC sensitivity before the start of therapy could allow more individualized GC therapy. The aim of the study was to investigate the association between in vitro and in vivo GC sensitivity in RA.

Methods

Thirty-eight early and 37 established RA patients were prospectively studied. In vitro GC sensitivity was assessed with dexamethasone-induced effects on interleukin-2 (IL-2) and glucocorticoid-induced leucine zipper (GILZ) messenger RNA expression in peripheral blood mononuclear cells (PBMCs). A whole-cell dexamethasone-binding assay was used to measure number and affinity (1/KD) of glucocorticoid receptors (GRs).

In vivo GC sensitivity was determined by measuring the disease activity score (DAS) and health assessment questionnaire disability index (HAQ-DI) score before and after 2 weeks of standardized GC treatment.

Results

GR number was positively correlated with improvement in DAS. IL-2-EC50 and GILZ-EC50 values both had weak near-significant correlations with clinical improvement in DAS in intramuscularly treated patients only. HAQ responders had lower GILZ-EC50 values and higher GR number and KD.

Conclusions

Baseline cellular in vitro glucocorticoid sensitivity is modestly associated with in vivo improvement in DAS and HAQ-DI score after GC bridging therapy in RA. Further studies are needed to evaluate whether in vitro GC sensitivity may support the development of tailor-made GC therapy in RA.
Reversal by RARα agonist Am580 of c-Myc-induced imbalance in RARα/RARγ expression during MMTV-Myc tumorigenesis
Authors: Bosch Almudena , Bertran Silvina P , Lu Yongke , Garcia Avalon , Jones Alexis M , Dawson Marcia I , Farias Eduardo F
Published: August 2012

Introduction

Retinoic acid signaling plays key roles in embryonic development and in maintaining the differentiated status of adult tissues. Recently, the nuclear retinoic acid receptor (RAR) isotypes α, β and γ were found to play specific functions in the expansion and differentiation of the stem compartments of various tissues. For instance, RARγ appears to be involved in stem cell compartment expansion, while RARα and RARβ are implicated in the subsequent cell differentiation. We found that over-expressing c-Myc in normal mouse mammary epithelium and in a c-Myc-driven transgenic model of mammary cancer, disrupts the balance between RARγ and RARα/β in favor of RARγ.

Methods

The effects of c-Myc on RAR isotype expression were evaluated in normal mouse mammary epithelium, mammary tumor cells obtained from the MMTV-Myc transgenic mouse model as well as human normal immortalized breast epithelial and breast cancer cell lines. The in vivo effect of the RARα-selective agonist 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carboxamido]benzoic acid (Am580) was examined in the MMTV-Myc mouse model of mammary tumorigenesis.

Results

Modulation of the RARα/β to RARγ expression in mammary glands of normal mice, oncomice, and human mammary cell lines through the alteration of RAR-target gene expression affected cell proliferation, survival and tumor growth. Treatment of MMTV-Myc mice with the RARα-selective agonist Am580 led to significant inhibition of mammary tumor growth (~90%, P<0.001), lung metastasis (P<0.01) and extended tumor latency in 63% of mice. Immunocytochemical analysis showed that in these mice, RARα responsive genes such as Cyp26A1, E-cadherin, cellular retinol-binding protein 1 (CRBP1) and p27, were up-regulated. In contrast, the mammary gland tumors of mice that responded poorly to Am580 treatment (37%) expressed significantly higher levels of RARγ. In vitro experiments indicated that the rise in RARγ was functionally linked to promotion of tumor growth and inhibition of differentiation. Thus, activation of the RARα pathway is linked to tumor growth inhibition, differentiation and cell death.

Conclusions

The functional consequence of the interplay between c-Myc oncogene expression and the RARγ to RARα/β balance suggests that prevalence of RARγ over-RARα/β expression levels in breast cancer accompanied by c-Myc amplification or over-expression in breast cancer should be predictive of response to treatment with RARα-isotype-specific agonists and warrant monitoring during clinical trials.

See related editorial by Garattini et al http://breast-cancer-research.com/content/14/5/111
Imaging and quantifying salt-tracer transport in a riparian groundwater system by means of 3D ERT monitoring
Authors: Doetsch Joseph , Linde Niklas , Vogt Tobias , Binley Andrew , Green Alan G.
Published: August 2012

Determining groundwater flow paths of infiltrated river water is necessary for studying biochemical processes in the riparian zone, but their characterization is complicated by strong temporal and spatial heterogeneity. We investigated to what extent repeat 3D surface electrical resistance tomography (ERT) can be used to monitor transport of a salt-tracer plume under close to natural gradient conditions. The aim is to estimate groundwater flow velocities and pathways at a site located within a riparian groundwater system adjacent to the perialpine Thur River in northeastern Switzerland. Our ERT time-lapse images provide constraints on the plume’s shape, flow direction, and velocity. These images allow the movement of the plume to be followed for 35 m. Although the hydraulic gradient is only 1.43‰, the ERT time-lapse images demonstrate that the plume’s center of mass and its front propagate with velocities of [Formula: see text] and [Formula: see text], respectively. These velocities are compatible with groundwater resistivity monitoring data in two observation wells 5 m from the injection well. Five additional sensors in the 5–30 m distance range did not detect the plume. Comparison of the ERT time-lapse images with a groundwater transport model and time-lapse inversions of synthetic ERT data indicate that the movement of the plume can be described for the first 6 h after injection by a uniform transport model. Subsurface heterogeneity causes a change of the plume’s direction and velocity at later times. Our results demonstrate the effectiveness of using time-lapse 3D surface ERT to monitor flow pathways in a challenging perialpine environment over larger scales than is practically possible with crosshole 3D ERT.
Randomised, double-blind, placebo-controlled study of olanzapine
in patients with bipolar I depression
Authors: Tohen Mauricio , McDonnell David P. , Case Michael , Kanba Shigenobu , Ha Kyooseob , Fang Yi Ru , Katagiri Hideaki , Gomez Juan-Carlos
Published: August 2012

Background

Atypical antipsychotics are widely used in bipolar mania. However, the
efficacy of atypical antipsychotics in bipolar depression has not been
comprehensively explored.

Aims

To evaluate olanzapine monotherapy in patients with bipolar
depression.

Method

Patients with bipolar depression received olanzapine (5–20mg/day,
n = 343) or placebo (n = l71) for 6
weeks. The primary outcome was change from baseline to end-point in
Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary
outcomes included: Clinical Global impression - Bipolar Version (CGI-BP)
scale, 17-item Hamilton Rating Scale for Depression (HRSD-17) and Young
Mania Rating Scale (YMRS) scores, and the rate of response (≥50%
reduction in MADRS at end-point), recovery (MADRS ≤12 for ≥4 weeks plus
treatment completion) and remission (MADRS ≤8). The trial was registered
with ClinicalTrials.gov (NCT00510146).

Results

Olanzapine demonstrated: significantly greater
(P<0.04) improvements on MADRS (least-squares mean
change -13.82 v. -11.67), HRSD-17 and YMRS total scores
and all CGI-BP subscale scores v. placebo; significantly
(P≤0.05) more response and remission, but not
recovery; significantly (P<0.01) greater mean
increases in weight, fasting cholesterol and triglycerides; and
significantly more (P<0.001) patients gained ≥7% body
weight.

Conclusions

Olanzapine monotherapy appears to be efficacious in bipolar depression.
Additional long-term studies are warranted to confirm these results.
Safety findings were consistent with the known safety profile of
olanzapine.
Timing and expression of the Angiopoietin-1/Tie-2 pathway in murine lung development and congenital diaphragmatic hernia (CDH)
Authors: Grzenda Adrienne , Shannon John , Fisher Jason , Arkovitz Marc S.
Published: August 2012

Congenital Diaphragmatic Hernia (CDH) is one of the most common congenital abnormalities. Children born with CDH suffer a number of co-morbidities, the most serious of which is respiratory insufficiency from a combination of alveolar hypoplasia and pulmonary vascular hypertension. All children born with CDH display some degree of pulmonary hypertension, the severity of which has been correlated with mortality. The molecular mechanisms responsible for the development of pulmonary hypertension in CDH remain poorly understood. Ang-1, a central mediator in angiogenesis, participates in the vascular development of many tissues, including the lung. Although previous studies have demonstrated that Ang-1 may play an important role in the development of familial pulmonary hypertension, the role of Ang-1 in the development of the pulmonary hypertension associated with CDH is poorly understood. Here we report that Ang-1 appears important to murine lung development, establishing its tissue-level expression and localization patterns at key timepoints. Additionally, our data from a nitrofen/bisdiamine-induced murine model of CDH suggests that altered expression patterns of Ang-1, its receptor, Tie-2, and one of its transcription factors, Epithelium-specific Ets transcription factor 1 (ESE-1), may be responsible for the development of pulmonary hypertension in the setting of CDH.
Osteopontin deficiency delays inflammatory infiltration and the onset of muscle regeneration in a model of muscle injury
Authors: Uaesoontrachoon Kitipong , Wasgewatte Wijesinghe Dimuthu K. , Mackie Eleanor J. , Pagel Charles N.
Published: August 2012

Osteopontin is secreted by skeletal muscle myoblasts and stimulates their proliferation. Expression of osteopontin in skeletal muscle is up-regulated in pathological conditions including Duchenne muscular dystrophy, and recent evidence suggests that osteopontin may influence the course of this disease. The current study was undertaken to determine whether osteopontin regulates skeletal muscle regeneration, using a whole muscle autografting model of regeneration in osteopontin-null and wildtype mice. Osteopontin expression was found to be strongly up-regulated in wildtype grafts during the initial degeneration and subsequent early regeneration phases that are observed in this model. Grafted muscles from osteopontin-null mice degenerated more slowly than those of wildtype mice, as determined by histological assessment, fibre diameter and fibre number. The delayed degeneration in osteopontin-null grafts was associated with a delay in neutrophil and macrophage infiltration. Centrally nucleated (regenerating) muscle fibres also appeared more slowly in osteopontin-null grafts than in wildtype grafts. These results demonstrate that osteopontin plays a non-redundant role in muscle remodelling following injury.
π-Electron-system-layered Polymers Based on [2.2]Paracyclophane
Authors: Morisaki Yasuhiro , Chujo Yoshiki
Published: August 2012

Incorporation of a [2.2]paracyclophane skeleton into a conjugated polymer main chain affords a polymer comprising stacked π-electron systems. In this article, we describe the synthesis and optical properties of some [2.2]paracyclophane-based polymers on the basis of the results of our resent research. We discuss the role of [2.2]paracyclophane in the polymer backbone, through-space conjugation of the polymer, and the feasibility of using the titled polymers as single molecular wires that allow for unidirectional energy and charge transfer via through-space interactions.
Amorphous Titanium Sulfide Electrode for All-solid-state Rechargeable Lithium Batteries with High Capacity
Authors: Hayashi Akitoshi , Matsuyama Takuya , Sakuda Atsushi , Tatsumisago Masahiro
Published: August 2012

Amorphous TiS3 active materials were prepared using a high-energy ball mill and first applied to all-solid-state cells with Li2S–P2S5 solid electrolyte. The solid-state cell operated as a rechargeable lithium battery with a high capacity of 400 mA h g−1 at room temperature. The cell exhibited a higher capacity than a solid-electrolyte cell with crystalline TiS2 and showed better cyclability than a liquid-electrolyte cell with crystalline TiS3.
Synthesis of AlPO-5 at Low Temperature by Controlling the Kinetics of Conversion of Aluminophosphate Phases
Authors: Tanahashi Shinya , Moteki Takahiko , Okubo Tatsuya
Published: August 2012

We found that AlPO-5 crystals can be synthesized at relatively low temperature (120 °C) by hydrothermal reaction. The critical requirement was the adjustment of the gel composition to control the crystallization rates of aluminophosphate phases. The obtained products showed almost the same pore characteristics compared with the reference products synthesized at high temperature.
Significant Improvement of Photovoltaic Performance of Dye-sensitized Solar Cells by Using 4-Trimethylsilylpyridine as Organic Additive to Electrolyte Solution
Authors: Kakiage Kenji , Tsukahara Takashi , Kyomen Toru , Unno Masafumi , Hanaya Minoru
Published: August 2012

The applicability of 4-trimethylsilylpyridine (4TMSpy) was investigated as an organic additive to the electrolyte solution of dye-sensitized solar cells. The N3-sensitized solar cell with 4TMSpy showed higher light-to-electric energy conversion efficiencies than that with the ordinary organic additive of 4-tert-butylpyridine by a factor of ca. 1.1. This improvement of the photovoltaic performance was considered to be due to the bulkiness and peculiar electronic properties of the trimethylsilyl group.
Highly Efficient Circularly Polarized Light Emission in the Green Region from Chiral Polyfluorene–Thiophene Thin Films
Authors: Hirahara Takashi , Yoshizawa-Fujita Masahiro , Takeoka Yuko , Rikukawa Masahiro
Published: August 2012

A chiral polyfluorene–thiophene derivative incorporating two different chiral side chains was synthesized via the Suzuki coupling reaction. Upon photoexcitation, thin films of the polymer exhibited efficient circularly polarized luminescence in the visible range, even without thermal annealing. The dissymmetry factor, glum, of films with thicknesses less than 100 nm reached 0.2 at 505 nm.
Host–Guest-bridge Induces Irreversible Helix Folding in a Short Peptide
Authors: Nakamura Yuki , Nakazawa Kazuya , Hamasaki Keita
Published: August 2012

Short peptides with or without host–guest-bridges on their side chains were prepared and the helix content was examined in the absence or in the presence of the host–guest-bridge breaker. While a short peptide without host–guest-bridge had 14% helix content, a short peptide with host–guest-bridge had 40% helix. This helix content hardly changed after the host–guest-bridge was removed. Host–guest-bridge acts as an initiator for helix folding in the short peptide.
Facile Synthesis of Single-sized Colloidal CdTe Assemblies Exhibiting Bright Band Gap Photoemission
Authors: Wang Jidong , Zhai Jizu , Han Shumin
Published: August 2012

A facile synthetic strategy to prepare single-sized colloidal CdTe assemblies with bright band gap emission is described in this letter. In contrast to traditional approaches, the preparation of trioctylphosphine telluride (TOPTe) was not required for this synthesis, and our approach follows a one-step reaction. The CdTe magic-sized quantum dot (MSQD) assemblies were sequentially grown in this approach, and the thermodynamic equilibrium of CdTe MSQDs sequential growth was proposed.