bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA
Therapy for Polyglutamine Neurodegenerative Diseases
Authors: Smith Danielle C , Watson Lauren M , Greenberg Jacquie LJ , Wood Matthew JA , Scholefield Janine 
Published: April 2013

Abstract

The polyglutamine neurodegenerative diseases are caused by the expansion of a CAG repeat, which is translated into an extended polyglutamine tract in the disease‐causing protein. Although arising from a common type of mutation, the mechanisms by which each polyglutamine protein exerts its cellular toxicity are complex. RNA‐based approaches represent promising therapeutic strategies, offering the potential to target and suppress the expression of polyglutamine disease genes in a sequence‐specific manner, upstream of the deleterious effects of the mutant protein. In particular, allele‐specific therapies, which selectively silence the mutant copy of the gene while retaining the wild‐type function, may prove useful in cases where wild‐type gene expression is known to be indispensable. With a variety of RNA technologies currently being developed to target multiple polyglutamine disease genes, the initiation of clinical trials appears imminent. However, the numerous challenges associated with design, dosage and delivery optimisation must be addressed before such therapies can be effectively applied in a clinical setting.

Key Concepts:

The elucidation of an effective therapy for any of the inherited polyglutamine repeat disorders may contribute to the alleviation of the global health burden.

Because many of the polyglutamine pathogenic mechanisms involve the toxic protein and its intermediates, the most logical therapeutic strategy may be to prevent pathogenesis upstream of these effects.

Gene‐based therapies have been heralded as the most promising avenue for therapeutic research, because they may allow for prevention or reversal of disease progression through altering the expression, processing or conformation of the mutant protein.

Various RNA‐based targeting strategies for the polyglutamine repeat disorders have been explored, including repeat targeting, allele‐specific silencing, nonallele‐specific silencing and gene knockdown and replacement.

Numerous guidelines exist for the design, delivery and dosage of therapeutic effectors.

Cell‐based and animal models have contributed significantly towards the testing and improvement of potential therapies, paving the way to clinical application.
Mixed Aerogels from Au and CdTe Nanoparticles
Authors: Hendel Thomas , Lesnyak Vladimir , Kühn Laura , Herrmann Anne‐Kristin , Bigall Nadja C. , Borchardt Lars , Kaskel Stefan , Gaponik Nikolai , Eychmüller Alexander 
Published: April 2013

AbstractMixed metal–semiconductor nanocrystal aerogels are fabricated, which are light‐emitting and highly porous macroscopic monoliths. Thiol‐stabilized CdTe and Au nanoparticles from aqueous synthesis act as building blocks for the hybrid material. The Au colloids undergo a surface‐modification to enhance the particle stability and achieve thiol functionalities. A photochemical treatment is applied for the gelation process which is found to be reversible by subsequent addition of thiol molecules. Via supercritical drying aerogels are formed. The variation of the initial CdTe to Au nanoparticle ratio permits a facile tuning of the content and the properties of the resulting aerogels. The obtained structures were characterized by means of optical spectroscopy, electron microscopy, elemental analysis, and nitrogen physisorption.
Novel ways to assess forested wetland restoration in North Carolina using ecohydrological patterns from reference sites
Authors: Johnson Yari Ben , Shear Theodore Henry , James April Lynda 
Published: April 2013

ABSTRACTRestoring jurisdictional wetland hydrology does not ensure that the hydrologic conditions of any specific natural forested wetland community are recreated. This is especially problematic for a state like North Carolina, which has roughly two dozen different forested wetland communities. Because forested wetland communities align themselves across edaphic and hydrologic gradients, we suggest exploiting these relationships to guide restoration design and set performance standards. However, methods to compare hydrology between multiple reference sites and restored wetlands are lacking. To address this, we studied three different forested wetlands across 13 reference sites to determine which measures of water table levels, based on correlation with plant community composition, would be useful to distinguish these three communities. We then used the best measures of water table levels to assess two restoration sites and compare them with the reference sites. Our results showed that monthly median water table levels encompassing the start of the growing season had the strongest correlation with plant community composition, whereas roughly five other measures also had strong correlations. On the basis of the best measures, both of the restoration sites had water table levels that generally fell within the natural range of the reference sites. Because there was variation in water table levels across each restoration site, the different measures where useful to identify which areas were least similar to the reference sites and might need further monitoring in the future. On the basis of our results, we recommend using community‐specific measures of hydrology to guide and assess forested wetland restoration. Copyright © 2013 John Wiley & Sons, Ltd.
Factors associated with help‐seeking behaviors in Mexican older individuals with depressive symptoms: a cross‐sectional study
Authors: Pérez‐Zepeda Mario Ulises , Arango‐Lopera Victoria Eugenia , Wagner Fernando A. , Gallo Joseph J. , Sánchez‐García Sergio , Juárez‐Cedillo Teresa , García‐Peña Carmen 
Published: April 2013

ObjectiveDepression in the older individuals is associated with multiple adverse outcomes, such as high health service utilization rates, low pharmacological compliance, and synergistic interactions with other comorbidities. Moreover, the help‐seeking process, which usually starts with the feeling “that something is wrong” and ends with appropriate medical care, is influenced by several factors.The aim of this study was to explore factors associated with the pathway of help seeking among older adults with depressive symptoms.MethodsA cross‐sectional study of 60‐year or older community dwelling individuals belonging to the largest health and social security system in Mexico was carried out. A standardized interview explored the process of seeking health care in four dimensions: depressive symptoms, help seeking, help acquisition, and specialized mental health.ResultsA total of 2322 individuals were studied; from these, 67.14% (n = 1559) were women, and the mean age was 73.18 years (SD = 7.02); 57.9% had symptoms of depression; 337 (25.1%) participants sought help, and 271 (80.4%) received help; and 103 (38%) received specialized mental health care. In the stepwise model for not seeking help (χ2 = 81.66, p < 0.0001), significant variables were female gender (odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.511–0.958, p = 0.026), health‐care use (OR 3.26, CI 95% 1.64–6.488, p = 0.001). Number of years in school, difficulty in activities, Short Anxiety Screening Test score, and indication that depression is not a disease belief were also significant.ConclusionsAppropriate mental health care is rather complex and is influenced by several factors. The main factors associated with help seeking were gender, education level, recent health service use, and the belief that depression is not a disease. Detection of subjects with these characteristics could improve care of the older individuals with depressive symptoms. Copyright © 2013 John Wiley & Sons, Ltd.
Synthesis of Dihydrothienopyridine Derivatives Fused with Triazole Rings
Authors: Ábrányi‐Balogh Péter , Milen Mátyás , Dancsó András , Frigyes Dávid , Pongó László , Keglevich György 
Published: April 2013

ABSTRACTNew dihydro[3,2‐c][1,2,4]triazolo[4,3‐a]pyridines were synthesized by the reaction of 4‐(methylsulfanyl)‐6,7‐dihydrothieno[3,2‐c]pyridine with acid hydrazides. One bis(dihydrothienotriazolo‐pyridine) was also prepared. In a few cases, the corresponding intermediate could be detected by LC‐MS. The bromophenyl derivative was involved in Suzuki and Sonogashira cross‐coupling reactions. © 2013 Wiley Periodicals, Inc. Heteroatom Chem 24:226–233, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21087
Hip bone loss is attenuated with 1000 IU but not 400 IU daily vitamin D3: A 1-year double-blind RCT in postmenopausal women
Authors: Macdonald Helen M , Wood Adrian D , Aucott Lorna S , Black Alison J , Fraser William D , Mavroeidi Alexandra , Reid David M , Secombes Karen R , Simpson William G , Thies Frank 
Published: April 2013

ABSTRACT

Few year-long vitamin D supplementation trials exist that match seasonal changes. The aim of this study was to determine whether daily oral vitamin D3 at 400 IU or 1000 IU compared with placebo affects annual bone mineral density (BMD) change in postmenopausal women in a 1-year double-blind placebo controlled trial in Scotland. White women aged 60 to 70 years (n = 305) were randomized to one of two doses of vitamin D or placebo. All participants started simultaneously in January/February 2009, attending visits at bimonthly intervals with 265 (87%) women attending the final visit and an additional visit 1 month after treatment cessation. BMD (Lunar iDXA) and 1,25-dihydroxyvitamin D[1,25(OH)2D], N-terminal propeptide of type 1 collagen [P1NP], C-terminal telopeptide of type I collagen [CTX], and fibroblast growth factor-23 [FGF23] were measured by immunoassay at the start and end of treatment. Circulating PTH, serum Ca, and total 25-hydroxyvitamin D [25(OH)D] (latter by tandem mass spectrometry) were measured at each visit. Mean BMD loss at the hip was significantly less for the 1000 IU vitamin D group (0.05% ± 1.46%) compared with the 400 IU vitamin D or placebo groups (0.57% ± 1.33% and 0.60% ± 1.67%, respectively) (p &lt; 0.05). Mean (± SD) baseline 25(OH)D was 33.8 ± 14.6 nmol/L; comparative 25(OH)D change for the placebo, 400 IU, and 1000 IU vitamin D groups was −4.1 ± 11.5 nmol/L, +31.6 ± 19.8 nmol/L, and +42.6 ± 18.9 nmol/L, respectively. Treatment did not change markers of bone metabolism, except for a small reduction in PTH and an increase in serum calcium (latter with 1000 IU dose only). The discordance between the incremental increase in 25(OH)D between the 400 IU and 1000 IU vitamin D and effect on BMD suggests that 25(OH)D may not accurately reflect clinical outcome, nor how much vitamin D is being stored. © 2013 American Society for Bone and Mineral Research.
Analysis of the West African Monsoon system in the regional climate model COSMO‐CLM
Authors: Kothe S. , Lüthi D. , Ahrens B. 
Published: April 2013

ABSTRACTThe West African Monsoon (WAM) is a major component of the global monsoon system. The contrast between land surface temperature (LST) (in the Sahel and Sahara) and sea surface temperature (SST) dominates the WAM formation. This study investigated the WAM representation, and the impact of surface temperature uncertainties in three regional climate simulations with the model COnsortium for Small‐scale MOdelling‐Climate Limited‐area Model (COSMO‐CLM) (grid‐spacing: 0.44°). The regional simulations were driven by present‐day climate simulations with the global climate model ECHAM5 (grid‐spacing: ∼1.9°), and by the re‐analysis data ERA‐Interim (∼0.7°). The WAM dynamics were quantified using the WAM wind shear index (WAMI). In addition, indices for outgoing long‐wave radiation (OLR) (an indicator for convective clouds), and total precipitation were used to assess monsoon characteristics. The large‐scale patterns of precipitation were adequately reproduced by COSMO‐CLM compared to observations, but there were significant uncertainties at regional scales, such as a strong overestimation of precipitation in the Sahel. The model also significantly overestimated convective activity and simulated a too intense monsoon circulation as indicated by WAMI. The impact of bare soil albedo on LST was investigated by implementing an MODIS‐observation based bare‐soil albedo parameterization, which led to a reduction of the simulated warm bias in the Sahara region during the monsoon season by up to 3 K, and an improvement of simulated Sahel precipitation. However, the simulated monsoon circulation was not improved. Using either ERA‐Interim or ECHAM5 at the lateral boundaries showed that the COSMO‐CLM results were very sensitive to the driving data. And, on coarse grid‐scales (of the order of the grid‐spacing of the driving datasets) the regional climate model was not able to perform substantially better than the forcing data. The differently driven COSMO‐CLM simulations also indicated that the land–sea temperature gradient, and its impact on WAM, is dominated by SST and less by LST (in Sahara and Sahel).
Polymerized Ionic Liquid as Stabilizer in Aqueous Emulsion Polymerization Enables a Hydrophilic–Hydrophobic Transition during Film Formation
Authors: Rozik Nehad , Antonietti Markus , Yuan Jiayin , Tauer Klaus 
Published: April 2013

AbstractPolymerized ionic liquid (PIL) nanoparticles are for the first time applied as sole stabilizers in aqueous emulsion polymerization and reveal an astonishing and unexpected behavior. In a well‐dispersed state, the PIL nanoparticles serve as an unexpectedly effective stabilizer for polystyrene dispersions, enabling solids content of greater than 40%. However, the same PIL as dry powder is hydrophobic and, in accordance with Bancroft's rule, unable to stabilize aqueous dispersions. This ambivalent behavior of PIL is extremely beneficial for the application of aqueous dispersions because, as desired for decades, the hydrophilic dispersed state during synthesis turns hydrophobic in the dried state during application of the polymer.
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The visceral adiposity index as a predictor of insulin resistance in young women with polycystic ovary syndrome
Authors: Oh Jee‐Young , Sung Yeon‐Ah , Lee Hye Jin 
Published: April 2013

ObjectiveVisceral fat accumulation is more strongly related to insulin resistance than to excess total adiposity. The visceral adiposity index (VAI) has recently been suggested as an indicator of the visceral adiposity measured by magnetic resonance imaging. To evaluate whether the VAI could replace visceral computed tomography (CT) scanning and predict insulin resistance in young women with polycystic ovary syndrome (PCOS) was presented.Design and MethodsOne hundred and eighty Korean women aged 16‐41 years who were diagnosed with PCOS using the Rotterdam criteria were included. The VAI was derived from a formula using body mass index, waist circumference, triglycerides, and high‐density lipoprotein cholesterol. Visceral adiposity was defined as a visceral fat area (VFA) measuring > 100 cm2 by CT scanning. Insulin sensitivity was evaluated by insulin‐mediated glucose utilization (M value), which was obtained using a euglycemic hyperinsulinemic clamp.ResultsThe VAI positively correlated with VFA, the visceral‐to‐subcutaneous fat ratio, and systolic and diastolic blood pressure, and negatively correlated with the M value. In a linear regression analysis, the VAI was an independent determinant of the insulin sensitivity after controlling for age, systolic blood pressure, fasting glucose, fasting insulin, and testosterone levels. In a logistic regression analysis, the VAI odds ratio was 3.5 (95% CI 1.2‐9.8) for predicting visceral adiposity after controlling for the various metabolic parameters and testosterone.ConclusionThe VAI can replace visceral CT scanning as a marker for visceral adiposity, and it predicts insulin resistance in young women with PCOS.
Oxidative stress and inflammatory markers in relation to circulating levels of adiponectin
Authors: Gustafsson Stefan , Lind Lars , Söderberg Stefan , Zilmer Mihkel , Hulthe Johannes , Ingelsson Erik 
Published: April 2013

ObjectivePrevious epidemiological studies together with animal studies have suggested an association between adiponectin and oxidative stress and inflammation, but community‐based studies are lacking. Our objective was to investigate the relative importance of oxidative stress and inflammatory markers, representing different pathways in relation to adiponectin.Design and MethodsIn a cross‐sectional sample of 929 70‐year‐old individuals (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors study, relations between serum adiponectin and oxidative stress [conjugated dienes (CD), homocysteine, total antioxidant capacity, oxidized low‐density lipoprotein (OxLDL), OxLDL antibodies, baseline CD of LDL, glutathione (GSH), total glutathione (TGSH), glutathione disulfide], circulation interleukins (IL‐6, IL‐8), other cytokines [tumor necrosis factor α, monocyte chemotactic protein‐1 (MCP‐1), epidermal growth factor (EGF), vascular endothelial growth factor], cell adhesion molecules (vascular cell adhesion molecule‐1, intercellular adhesion molecule‐1, E‐selectin, P‐selectin, L‐selectin), and systemic inflammatory markers [C‐reactive protein (CRP), leukocyte count] in separate models were investigated.ResultsIn age‐ and sex‐adjusted, as well as multivariable‐adjusted models, adiponectin was significantly and positively associated with GSH, log TGSH, whereas an inverse association was observed for CD and log EGF. An inverse association between adiponectin and MCP‐1, log E‐selectin, and log CRP was significant in age‐ and sex‐adjusted models, but not in multivariable‐adjusted models.ConclusionsOur results imply that higher levels of adiponectin are associated with a more beneficial oxidative stress profile, with higher levels of principal anti‐oxidative GSH and total GSH together with lower levels of lipid peroxidation, possibly through shared pathways. Further studies are needed to investigate whether changes in the oxidative stress profile may be a mechanism linking adiponectin with type 2 diabetes and/or cardiovascular disease.
Harm Reduction Behaviors among Young Polysubstance Users at Raves
Authors: Fernández-Calderón Fermín , Lozano-Rojas Óscar , Rojas-Tejada Antonio , Bilbao-Acedos Izaskun , Vidal-Giné Claudio , Vergara-Moragues Esperanza , González-Saiz Francisco 
Published: April 2013

Background Raves may be considered recreational settings in which drug use and health risks related to polydrug use are higher than in others. Harm reduction behaviors implemented by ravers are of particular relevance in reducing such risks. This study analyzes harm reduction behaviors and their relationship to raver polysubstance use patterns. Methods Cross-sectional study of 248 ravers recruited at underground raves in Andalusia (Spain). A questionnaire was developed to collect information about their sociodemographics, drug use, and harm reduction behaviors. Results The results show that ravers employ harm reduction behaviors for minimizing drug-related harm. Nevertheless, only a small minority of the participants frequently employed harm reduction behavior for polysubstance use as well. Ravers identified as high polysubstance users protected themselves significantly less than those identified as low polysubstance users. Conclusions This study provides empirical information that may be useful for harm reduction intervention in a hidden and hard-to-reach population like rave attendees. The results point to the need to inform and increase harm reduction behavior specifically aimed at polysubstance use by ravers, especially among more frequent users. Future directions for research are also suggested.
Does Change in Alliance Impact Alcohol Treatment Outcomes?
Authors: Kan Lisa Y. , Henderson Craig E. , von Sternberg Kirk , Wang Wei 
Published: April 2013

Background Although both researchers and practitioners widely recognize therapeutic alliance's importance in general psychotherapy, studies specific to alcohol use treatments have produced mixed results and generally do not investigate if and how alliance changes over course of treatment. Methods Using parallel process latent growth curve modeling, the authors examined if increase in alliance was associated with reduced drinking behaviors and a statistical mediator in the relationship between treatment modality and outcome. The authors used data from Project MATCH ( J Stud Alcohol. 1997;58:7–29; Addiction. 1997;92:1671–1698), which investigated client-treatment matching effects for alcohol treatment among outpatient ( n = 952) and aftercare ( n = 774) participants randomized to cognitive behavioral treatment (CBT), 12-step facilitation (TSF), or motivational enhancement therapy (MET). Results Results indicate therapist-rated alliance increased significantly for CBT and TSF participants, but not MET. Participants across modalities in both samples evidenced the largest decrease in drinking behaviors from baseline to midtreatment and a slight deterioration in treatment gains from midtreatment to 15 months posttreatment. Alliance did not mediate the relationship between treatment modality and outcome, but increase in alliance was significantly related to decrease in drinking frequency. Conclusions These findings provide further justification for researchers to specifically design studies to examine change in alliance as a mechanism of change in alcohol treatments.
Stride frequency in relation to oxygen consumption in experienced and novice runners
Authors: de Ruiter Cornelis J. , Verdijk Peter W. L. , Werker Wout , Zuidema Menno J. , de Haan Arnold 
Published: April 2013

AbstractWe hypothesised that experienced runners would select a stride frequency closer to the optimum (minimal energy costs) than would novice runners. In addition, we expected that optimal stride frequency could simply be determined by monitoring heart rate without measuring oxygen consumption (V̇O2). Ten healthy males (mean±s: 24±2 year) with no running training experience and 10 trained runners of similar age ran at constant treadmill speed corresponding to 80% of individual ventilatory threshold. For two days, they ran at seven different stride frequencies (self‐selected stride frequency±18%) imposed by a metronome. Optimal stride frequency was based on the minimum of a second‐order polynomial equation fitted through steady state V̇O2 at each stride frequency. Running cost (mean±s) at optimal stride frequency was higher (P < 0.05) in novice (236±31 ml O2·kg−1.km−1) than trained (189±13 ml O2·kg−1.km−1) runners. Self‐selected stride frequency (mean±s; strides.min−1) for novice (77.8±2.8) and trained runners (84.4±5.3) were lower (P < 0.05) than optimal stride frequency (respectively, 84.9±5.0 and 87.1±4.8). The difference between self‐selected and optimal stride frequency was smaller (P < 0.05) for trained runners. In both the groups optimal stride frequency established with heart rate was not different (P > 0.3) from optimal stride frequency based on V̇O2. In each group and despite limited variation between participants, optimal stride frequencies derived from V̇O2 and heart rate were related (r > 0.7; P < 0.05). In conclusion, trained runners chose a stride frequency closer to the optimum for energy expenditure than novices. Heart rate could be used to establish optimal stride frequency.