bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostacyclin Regulates Spinal Nociceptive Processing through Cyclic Adenosine Monophosphate–induced Translocation of Glutamate Receptors
Authors: Schuh Claus Dieter , Brenneis Christian , Zhang Dong Dong , Angioni Carlo , Schreiber Yannick , Ferreiros-Bouzas Nerea , Pierre Sandra , Henke Marina , Linke Bona , Nüsing Rolf , Scholich Klaus , Geisslinger Gerd 
Published: August 2013

Abstract

Background:
Prostacyclin (PGI2) is known to be an important mediator of peripheral pain sensation (nociception) whereas little is known about its role in central sensitization.

Methods:
The levels of the stable PGI2-metabolite 6-keto-prostaglandin F1α (6-keto-PGF1α) and of prostaglandin E2 (PGE2) were measured in the dorsal horn with the use of mass spectrometry after peripheral inflammation. Expression of the prostanoid receptors was determined by immunohistology. Effects of prostacyclin receptor (IP) activation on spinal neurons were investigated with biochemical assays (cyclic adenosine monophosphate-, glutamate release-measurement, Western blot analysis) in embryonic cultures and adult spinal cord. The specific IP antagonist Cay10441 was applied intrathecally after zymosan-induced mechanical hyperalgesia in vivo.

Results:
Peripheral inflammation caused a significant increase of the stable PGI2 metabolite 6-keto-PGF1α in the dorsal horn of wild-type mice (n = 5). IP was located on spinal neurons and did not colocalize with the prostaglandin E2 receptors EP2 or EP4. The selective IP-agonist cicaprost increased cyclic adenosine monophosphate synthesis in spinal cultures from wild-type but not from IP-deficient mice (n = 5–10). The combination of fluorescence-resonance–energy transfer–based cyclic adenosine monophosphate imaging and calcium imaging showed a cicaprost-induced cyclic adenosine monophosphate synthesis in spinal cord neurons (n = 5–6). Fittingly, IP activation increased glutamate release from acute spinal cord sections of adult mice (n = 13–58). Cicaprost, but not agonists for EP2 and EP4, induced protein kinase A–dependent phosphorylation of the GluR1 subunit and its translocation to the membrane. Accordingly, intrathecal administration of the IP receptor antagonist Cay10441 had an antinociceptive effect (n = 8–11).

Conclusion:
Spinal prostacyclin synthesis during early inflammation causes the recruitment of GluR1 receptors to membrane fractions, thereby augmenting the onset of central sensitization.
Simultaneous Electroencephalographic and Functional Magnetic Resonance Imaging Indicate Impaired Cortical Top–Down Processing in Association with Anesthetic-induced Unconsciousness
Authors: Jordan Denis , Ilg Rüdiger , Riedl Valentin , Schorer Anna , Grimberg Sabine , Neufang Susanne , Omerovic Adem , Berger Sebastian , Untergehrer Gisela , Preibisch Christine , Schulz Enrico , Schuster Tibor , Schröter Manuel , Spoormaker Victor , Zimmer Claus , Hemmer Bernhard , Wohlschläger Afra , Kochs Eberhard F. , Schneider Gerhard 
Published: August 2013

Abstract

Background:
In imaging functional connectivity (FC) analyses of the resting brain, alterations of FC during unconsciousness have been reported. These results are in accordance with recent electroencephalographic studies observing impaired top–down processing during anesthesia. In this study, simultaneous records of functional magnetic resonance imaging (fMRI) and electroencephalogram were performed to investigate the causality of neural mechanisms during propofol-induced loss of consciousness by correlating FC in fMRI and directional connectivity (DC) in electroencephalogram.

Methods:
Resting-state 63-channel electroencephalogram and blood oxygen level–dependent 3-Tesla fMRI of 15 healthy subjects were simultaneously registered during consciousness and propofol-induced loss of consciousness. To indicate DC, electroencephalographic symbolic transfer entropy was applied as a nonlinear measure of mutual interdependencies between underlying physiological processes. The relationship between FC of resting-state networks of the brain (z values) and DC was analyzed by a partial correlation.

Results:
Independent component analyses of resting-state fMRI showed decreased FC in frontoparietal default networks during unconsciousness, whereas FC in primary sensory networks increased. DC indicated a decline in frontal–parietal (area under the receiver characteristic curve, 0.92; 95% CI, 0.68–1.00) and frontooccipital (0.82; 0.53–1.00) feedback DC (P < 0.05 corrected). The changes of FC in the anterior default network correlated with the changes of DC in frontal–parietal (r
partial = +0.62; P = 0.030) and frontal–occipital (+0.63; 0.048) electroencephalographic electrodes (P < 0.05 corrected).

Conclusion:
The simultaneous propofol-induced suppression of frontal feedback connectivity in the electroencephalogram and of frontoparietal FC in the fMRI indicates a fundamental role of top–down processing for consciousness.
Medial Septal Cholinergic Neurons Modulate Isoflurane Anesthesia
Authors: Tai Siew Kian , Ma Jingyi , Leung L. Stan 
Published: August 2013

Abstract

Background:
Cholinergic drugs are known to modulate the response of general anesthesia. However, the sensitivity of isoflurane or other volatile anesthetics after selective lesion of septal cholinergic neurons that project to the hippocampus is not known.

Methods:
Male Long Evans rats had 192 immunoglobulin G-saporin infused into the medial septum (n = 10), in order to selectively lesion cholinergic neurons, whereas control, sham-lesioned rats were infused with saline (n = 12). Two weeks after septal infusion, the hypnotic properties of isoflurane and ketamine were measured using a behavioral endpoint of loss of righting reflex (LORR). Septal lesion was assessed by counting choline acetyltransferase–immunoreactive cells and parvalbumin-immunoreactive cells.

Results:
Rats with 192 immunoglobulin G-saporin lesion, as compared with control rats with sham lesion, showed a 85% decrease in choline acetyltransferase–immunoreactive, but not parvalbumin–immunoreactive, neurons in the medial septal area. Lesioned as compared with control rats showed increased isoflurane sensitivity, characterized by a leftward shift of the graph plotting cumulative LORR percent with isoflurane dose. However, lesioned and control rats were not different in their LORR sensitivity to ketamine. When administered with 1.375% isoflurane, LORR induction time was shorter, whereas emergence time was longer, in lesioned as compared with control rats. Hippocampal 62–100 Hz gamma power in the electroencephalogram decreased with isoflurane dose, with a decrease that was greater in lesioned (n = 5) than control rats (n = 5).

Conclusions:
These findings suggest a role of the septal cholinergic neurons in modulating the sensitivity to isoflurane anesthesia, which affects both induction and emergence. The sensitivity of hippocampal gamma power to isoflurane appears to indicate anesthesia (LORR) sensitivity.
Assessing Psychosocial Risk in Pediatric Inflammatory Bowel Disease
Authors: Pai Ahna L.H. , Tackett Alayna , Hente Elizabeth A. , Ernst Michelle M. , Denson Lee A. , Hommel Kevin A. 
Published: August 2013

ABSTRACTAim:The aim of this study was to present the preliminary psychometric properties of the Psychosocial Assessment Tool 2.0_General (PAT2.0_GEN), a brief screener for psychosocial risk in families of children with inflammatory bowel disease (IBD).Methods:Caregivers of 42 youth with IBD were recruited and administered a battery of measures including the PAT2.0_GEN and well‐validated measures of child emotional and behavioral functioning at baseline and at a 6‐month follow‐up.Results:Internal consistency for the PAT2.0_GEN total score was good (α = 0.82). Baseline was significantly associated with the 6‐month follow‐up (r= 0.79,P< 0.001). Significant correlations between the baseline PAT2.0 _GEN total score and caregiver‐reported Child Behavior Checklist total scores at baseline (r= 0.74,P< 0.001) and at a 6‐month follow‐up (r= 0.62,P< 0.001) support the content and predictive validity of the PAT2.0_GEN. Baseline PAT2.0_GEN was also significantly correlated with youth‐reported Child Behavior Checklist total scores at baseline (r= 0.37,P= 0.02) but not at the 6‐month follow‐up (r= 0.23,P= 0.17).Conclusions:A number of indicators support the concurrent and predictive utility of the PAT2.0_GEN. The PAT2.0_GEN is a promising tool for screening psychosocial risk that could facilitate the provision of psychosocial services to those patients most in need.
Importance of local vs. geographic variation in salt marsh plant quality for arthropod herbivore communities
Authors: Marczak Laurie B. , Więski Kazimierz , Denno Robert F. , Pennings Steven C. 
Published: August 2013

Summary

An important recent advance in food web ecology has been the application of theory regarding spatial gradients to studies of the factors that affect animal population dynamics. Building on extensive studies of the Spartina alterniflora food web at the local scale, we hypothesized that geographic variation in S. alterniflora quality is an important bottom‐up control on food web structure and that geographic variation in S. alterniflora quality would interact with the presence of predators and top omnivores to mediate herbivore densities.

We employed a four‐factor fully crossed experiment in which we (i) collected plants from high‐ and low‐latitude locations and grew them in a common garden and varied (ii) plant fertilization status (mimicking the plant quality differences due to marsh elevation), (iii) mesopredator density and (iv) omnivore density.

Our results suggest that the single most important factor mediating insect herbivore densities is local variation in plant quality – induced in our experiment by fertilization and demonstrated repeatedly as a consequence of marsh elevation.

Top‐down effects were generally weak and in those cases where predators did exert a significant suppressing effect on herbivores, that impact was itself mediated by host‐plant characteristics.

Finally, despite observed variation in plant quality with latitude, and the separately measurable effects of this variation on herbivores, geographic‐scale variation in plant quality was overwhelmed by local conditions in our experiments.

Synthesis. We suggest that a first‐order understanding of variation across large latitudinal ranges in the Spartina alterniflora arthropod food web must begin with local variation in plant quality, which provides strong bottom‐up forcing to herbivore populations. A second‐order understanding of the arthropod food web should consider the role of predation in controlling herbivores feeding on low‐quality plants. Finally, while latitudinal variation in plant quality probably explains some variation in herbivore densities, it is probably more of a response to herbivore pressure than a driver of the herbivore dynamics. Although extrapolating from local to geographic scales presents multiple challenges, it is an essential task in order for us to develop an understanding that is general rather than site‐specific.
Factors influencing radioiodine uptake after thyroid cancer surgery
Authors: Bai Jia Bin , Shakerian Rezvaneh , Westcott James David , Lichtenstein Meir , Miller Julie A. 
Published: August 2013

AbstractBackgroundTotal thyroidectomy followed by radioactive iodine (RAI) ablation is indicated for most patients with differentiated thyroid cancer. There have been no quantitative studies testing factors that affect uptake on post‐ablation whole body scan. We hypothesized greater RAI uptake in patients who underwent two‐stage total thyroidectomy (diagnostic hemithyroidectomy followed by completion thyroidectomy) compared to patients who underwent one‐stage total thyroidectomy.MethodsMedical records and whole body scan images of thyroid cancer patients were reviewed. Thyroid uptake as a percentage of Iodine‐131 dose was calculated for each scan. RAI uptake was compared to procedure type, central lymph node dissection (CLND), extrathyroidal invasion, presence of thyroiditis and pre‐operative diagnosis.ResultsOne hundred six patients who underwent total thyroidectomy and RAI ablation for differentiated thyroid cancer were included. There was a trend to higher RAI uptake in patients who had undergone two‐stage thyroidectomy compared to one‐stage thyroidectomy (P = 0.06). CLND was associated significantly lower RAI uptake (P = 0.003). On multivariate analyses, CLND was the only variable that retained statistical significance (P = 0.023). CLND was performed more often in patients undergoing one‐stage thyroidectomy (P = 0.001), as these patients' cancer diagnosis was known prior to surgery.ConclusionRAI uptake appeared higher in two‐stage thyroidectomy than one‐stage thyroidectomy. This difference may be attributed to CLND being performed more often in one‐stage thyroidectomy. These results add to the discussion about the role of CLND in surgery for differentiated thyroid cancer.
Allosteric interactions at adenosine A1 and A3 receptors: new insights into the role of small molecules and receptor dimerization
Authors: Hill Stephen J , May Lauren T , Kellam Barrie , Woolard Jeanette 
Published: August 2013

The purine nucleoside adenosine is present in all cells in tightly regulated concentrations. It is released under a variety of physiological and pathophysiological conditions to facilitate protection and regeneration of tissues. Adenosine acts via specific GPCRs to either stimulate cyclic AMP formation, as exemplified by Gs‐protein‐coupled adenosine receptors (A2A and A2B), or inhibit AC activity, in the case of Gi/o‐coupled adenosine receptors (A1 and A3). Recent advances in our understanding of GPCR structure have provided insights into the conformational changes that occur during receptor activation following binding of agonists to orthosteric (i.e. at the same binding site as an endogenous modulator) and allosteric regulators to allosteric sites (i.e. at a site that is topographically distinct from the endogenous modulator). Binding of drugs to allosteric sites may lead to changes in affinity or efficacy, and affords considerable potential for increased selectivity in new drug development. Herein, we provide an overview of the properties of selective allosteric regulators of the adenosine A1 and A3 receptors, focusing on the impact of receptor dimerization, mechanistic approaches to single‐cell ligand‐binding kinetics and the effects of A1‐ and A3‐receptor allosteric modulators on in vivo pharmacology.Linked ArticlesThis article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐5
Does Parental Involvement Matter for Student Achievement and Mental Health in High School?
Authors: Wang Ming‐Te , Sheikh‐Khalil Salam 
Published: August 2013

Parental involvement in education remains important for facilitating positive youth development. This study conceptualized parental involvement as a multidimensional construct—including school‐based involvement, home‐based involvement, and academic socialization—and examined the effects of different types of parental involvement in 10th grade on student achievement and depression in 11th grade (approximately ages 15–17 years). In addition, this study tested whether parental involvement influenced adolescent outcomes by increasing their academic engagement in school. A total of 1,056 adolescents participated in the study (51% males; 53% European American, 40% African American, and 7% other). Parental involvement was found to improve academic and emotional functioning among adolescents. In addition, parental involvement predicted adolescent academic success and mental health both directly and indirectly through behavioral and emotional engagement.
Adoptive Gay Father Families: Parent–Child Relationships and Children's Psychological Adjustment
Authors: Golombok Susan , Mellish Laura , Jennings Sarah , Casey Polly , Tasker Fiona , Lamb Michael E. 
Published: August 2013

Findings are presented on a U.K. study of 41 gay father families, 40 lesbian mother families, and 49 heterosexual parent families with an adopted child aged 3–9 years. Standardized interview and observational and questionnaire measures of parental well‐being, quality of parent–child relationships, child adjustment, and child sex‐typed behavior were administered to parents, children, and teachers. The findings indicated more positive parental well‐being and parenting in gay father families compared to heterosexual parent families. Child externalizing problems were greater among children in heterosexual families. Family process variables, particularly parenting stress, rather than family type were found to be predictive of child externalizing problems. The findings contribute to theoretical understanding of the role of parental gender and parental sexual orientation in child development.
A two‐yr prospective study of bone health in children after renal transplantation employing two imaging techniques
Authors: Christoforidis Athanasios , Printza Nikoleta , Gkogka Chrysa , Kazantzidou Eirini , Papachristou Fotios 
Published: August 2013

AbstractThe aim of this study was to prospectively and longitudinally evaluate bone properties with the use of two bone imaging techniques (dual energy X‐ray absorptiometry [DXA], and quantitative ultraSonography [QUS]) in pediatric renal transplant recipients. Fourteen patients (eight boys and six girls) with a mean age of 12.25 ± 3.11 yr (range: 8–17.5 yr) completed a two‐yr follow‐up. Measurements of bone mineral density (BMD) by DXA at lumbar spine and hip and speed of sound (SOS) by QUS at radius and tibia were performed at the beginning and at the end of the study. A significant improvement in mean Z‐score of SOS values measured at tibia (1.01 ± 1.31 vs. −0.46 ± 1.14, p = 0.005) was observed. On the contrary, mean Z‐score of BMD values measured at femoral neck was significantly reduced (−1.95 ± 2.15 vs. −0.33 ± 1.13, p = 0.041). Finally, multivariate stepwise regression analyses showed that glomerular filtration rate at the beginning of the study was the best predictor of the difference in BMD Z‐scores measured at lumbar spine. Additionally, values of intact parathormone (iPTH) at the beginning of the study and the change in iPTH throughout the study predicted the 72.3% of the difference in Z‐score of SOS measured at radius with an inverse relationship.
Do Clinical and Translational Science Graduate Students Understand Linear Regression? Development and Early Validation of the REGRESS Quiz
Authors: Enders Felicity 
Published: August 2013

AbstractIntroductionAlthough regression is widely used for reading and publishing in the medical literature, no instruments were previously available to assess students’ understanding. The goal of this study was to design and assess such an instrument for graduate students in Clinical and Translational Science and Public Health.MethodsA 27‐item REsearch on Global Regression Expectations in StatisticS (REGRESS) quiz was developed through an iterative process. Consenting students taking a course on linear regression in a Clinical and Translational Science program completed the quiz pre‐ and postcourse. Student results were compared to practicing statisticians with a master's or doctoral degree in statistics or a closely related field.ResultsFifty‐two students responded precourse, 59 postcourse , and 22 practicing statisticians completed the quiz. The mean (SD) score was 9.3 (4.3) for students precourse and 19.0 (3.5) postcourse (P < 0.001). Postcourse students had similar results to practicing statisticians (mean (SD) of 20.1(3.5); P = 0.21). Students also showed significant improvement pre/postcourse in each of six domain areas (P < 0.001). The REGRESS quiz was internally reliable (Cronbach's alpha 0.89).ConclusionThe initial validation is quite promising with statistically significant and meaningful differences across time and study populations. Further work is needed to validate the quiz across multiple institutions.
Comparison of cortical thickness in patients with early‐stage versus late‐stage amnestic mild cognitive impairment
Authors: Ye B. S. , Seo S. W. , Yang J.‐J. , Kim H. J. , Kim Y. J. , Yoon C. W. , Cho H. , Noh Y. , Kim G. H. , Chin J. , Kim J.‐H. , Jeon S. , Lee J. M. , Na D. L. 
Published: August 2013

Background and purposeDisappointing outcomes from clinical trials involving amyloid‐modifying therapies for Alzheimer's disease (AD) have prompted more focus on the concept of early‐stage (E) amnestic mild cognitive impairment (E‐aMCI). However, limited evidence suggests that E‐aMCI may represent aMCI at a very early stage of AD. Furthermore, the nature of the progression of E‐aMCI to late‐stage aMCI (L‐aMCI) remains unclear. Therefore, the aim of the present study was to characterize patterns of cortical thinning in both E‐aMCI and L‐aMCI patients.MethodsCortical thicknesses were measured in 190 patients with aMCI and 147 subjects with normal cognition. In accordance with memory test scores involving delayed recall items, aMCI patients were divided into two subgroups, containing 73 E‐aMCI subjects with milder memory impairment [scores between −1.5 standard deviation (SD) and −1.0 SD compared with age‐ and education‐matched norms] and 117 L‐aMCI subjects with more severe memory impairment (scores lower than −1.5 SD).ResultsCompared with controls, the E‐aMCI group exhibited cortical thinning in the left medial temporal and insular regions, whereas the L‐aMCI group showed cortical thinning in widespread regions, including the bilateral dorsolateral prefrontal, anterior and medial temporal, and temporo‐parietal association cortices, and the precuneus. When the two aMCI groups were directly compared, the L‐aMCI group showed greater cortical thinning in the right superior prefrontal, medial temporal, posterior cingulate and lateral parietal cortices.ConclusionOur findings suggest that E‐aMCI might represent an early symptomatic stage of AD. Furthermore, L‐aMCI might resemble AD more closely than E‐aMCI, in terms of the topography of cortical thinning.
Protein crystallography for aspiring crystallographers or how to avoid pitfalls and traps in macromolecular structure determination
Authors: Wlodawer Alexander , Minor Wladek , Dauter Zbigniew , Jaskolski Mariusz 
Published: August 2013

The number of macromolecular structures deposited in the Protein Data Bank now approaches 100 000, with the vast majority of them determined by crystallographic methods. Thousands of papers describing such structures have been published in the scientific literature, and 20 Nobel Prizes in chemistry or medicine have been awarded for discoveries based on macromolecular crystallography. New hardware and software tools have made crystallography appear to be an almost routine (but still far from being analytical) technique and many structures are now being determined by scientists with very limited experience in the practical aspects of the field. However, this apparent ease is sometimes illusory and proper procedures need to be followed to maintain high standards of structure quality. In addition, many noncrystallographers may have problems with the critical evaluation and interpretation of structural results published in the scientific literature. The present review provides an outline of the technical aspects of crystallography for less experienced practitioners, as well as information that might be useful for users of macromolecular structures, aiming to show them how to interpret (but not overinterpret) the information present in the coordinate files and in their description. A discussion of the extent of information that can be gleaned from the atomic coordinates of structures solved at different resolution is provided, as well as problems and pitfalls encountered in structure determination and interpretation.