bluuebunny/crossref_metadata_2025 huggingface dataset:
Heparin in pregnant women with previous placenta-mediated pregnancy complications: a prospective, randomized, multicenter, controlled clinical trial
Authors: Martinelli Ida , Ruggenenti Piero , Cetin Irene , Pardi Giorgio , Perna Annalisa , Vergani Patrizia , Acaia Barbara , Facchinetti Fabio , La Sala Giovanni Battista , Bozzo Maddalena , Rampello Stefania , Marozio Luca , Diadei Olimpia , Gherardi Giulia , Carminati Sergio , Remuzzi Giuseppe , Mannucci Pier Mannuccio
Published: January 2012

To assess whether antithrombotic prophylaxis with low-molecular-weight heparin effectively prevents recurrence of late pregnancy complications, 135 women with previous history of preeclampsia, hemolytic anemia, elevated liver enzymes and low platelet count syndrome, intrauterine fetal death, fetal growth restriction, or placental abruption who had been referred within the 12th gestational week were randomized to medical surveillance alone (n = 68) or combined to open-label nadroparin (3800 IU daily subcutaneous injections) treatment (n = 67) in the setting of a randomized, parallel-group, superiority trial, run in Italy from April 2007 to April 2010. Primary outcome was a composite end point of late-pregnancy complications. Analysis was by intention to treat. The study was stopped for futility at the time of the first planned interim analysis. Among the 128 women eventually available for final analyses, 13 of the 63 (21%) randomized to nadroparin compared with 12 of the 65 (18%) on medical surveillance alone progressed to the primary end point. The absolute event risk difference between treatment arms (2.2; −1.6 to 16.0) was not statistically significant (P = .76). Thus, nadroparin did not prevent late-pregnancy complications in women at risk of recurrence. This finding challenges the role of antithrombotic prophylaxis with low-molecular-weight heparin in the prevention of recurrent late pregnancy complications The trial was registered at http://ricerca-clinica.agenziafarmaco.it as EudraCT 2006-004205-26.
UT-B-deficient mice develop renal dysfunction and structural damage
Authors: Zhou Lei , Meng Yan , Lei Tianluo , Zhao Dan , Su Jing , Zhao Xuejian , Yang Baoxue
Published: January 2012

Background

Urea transporter UT-B is the major urea transporter in erythrocytes and the descending vasa recta in the kidney. In this study, we investigated the effects of long-term UT-B deficiency on functional and structural defect in the kidney of 16-and 52-week-old UT-B-null mice.

Methods

UT-B-knockout mice were generated by targeted gene disruption and lacked UT-B protein expression in all organs. The urinary concentrating ability of mice was studied in terms of daily urine output, urine osmolality, and urine and plasma chemistries. Changes in renal morphology were evaluated by hematoxylin and eosin staining.

Results

The UT-B-null mice showed defective urine concentrating ability. The daily urine output in UT-B-null mice (2.5 ± 0.1 ml) was 60% higher and urine osmolality (985 ± 151 mosm) was significantly lower than that in wild-type mice (1463 ± 227 mosm). The 52-week-old UT-B-null mice exhibited polyuria after water deprivation, although urine osmolality was increased. At 52 weeks of age, over 31% of UT-B-null mice exhibited renal medullary atrophy because of severe polyuria and hydronephrosis.

Conclusions

Long-term UT-B deficiency causes severe renal dysfunction and structural damage. These results demonstrate the important role of UT-B in countercurrent exchange and urine concentration.
Failure of available scoring systems to predict ongoing infection in patients with abdominal sepsis after their initial emergency laparotomy
Authors: van Ruler Oddeke , Kiewiet Jordy JS , Boer Kimberley R , Lamme Bas , Gouma Dirk J , Boermeester Marja A , Reitsma Johannes B
Published: January 2012

Background

To examine commonly used scoring systems, designed to predict overall outcome in critically ill patients, for their ability to select patients with an abdominal sepsis that have ongoing infection needing relaparotomy.

Methods

Data from a RCT comparing two surgical strategies was used. The study population consisted of 221 patients at risk for ongoing abdominal infection. The following scoring systems were evaluated with logistic regression analysis for their ability to select patients requiring a relaparotomy: APACHE-II score, SAPS-II, Mannheim Peritonitis Index (MPI), MODS, SOFA score, and the acute part of the APACHE-II score (APS).

Results

The proportion of patients requiring a relaparotomy was 32% (71/221). Only 2 scores had a discriminatory ability in identifying patients with ongoing infection needing relaparotomy above chance: the APS on day 1 (AUC 0.61; 95%CI 0.52-0.69) and the SOFA score on day 2 (AUC 0.60; 95%CI 0.52-0.69). However, to correctly identify 90% of all patients needing a relaparotomy would require such a low cut-off value that around 80% of all patients identified by these scoring systems would have negative findings at relaparotomy.

Conclusions

None of the widely-used scoring systems to predict overall outcome in critically ill patients are of clinical value for the identification of patients with ongoing infection needing relaparotomy. There is a need to develop more specific tools to assist physicians in their daily monitoring and selection of these patients after the initial emergency laparotomy.

Trial registration number

ISRCTN: ISRCTN 51729393
One-step generation of error-prone PCR libraries using Gateway® technology
Authors: Gruet Antoine , Longhi Sonia , Bignon Christophe
Published: January 2012

Background

Error-prone PCR (epPCR) libraries are one of the tools used in directed evolution. The Gateway® technology allows constructing epPCR libraries virtually devoid of any background (i.e., of insert-free plasmid), but requires two steps: the BP and the LR reactions and the associated E. coli cell transformations and plasmid purifications.

Results

We describe a method for making epPCR libraries in Gateway® plasmids using an LR reaction without intermediate BP reaction. We also describe a BP-free and LR-free sub-cloning method for in-frame transferring the coding sequence of selected clones from the plasmid used to screen the library to another one devoid of tag used for screening (such as the green fluorescent protein). We report preliminary results of a directed evolution program using this method.

Conclusions

The one-step method enables producing epPCR libraries of as high complexity and quality as does the regular, two-step, protocol for half the amount of work. In addition, it contributes to preserve the original complexity of the epPCR product.
The complexities of malaria disease manifestations with a focus on asymptomatic malaria
Authors: Laishram Dolie D , Sutton Patrick L , Nanda Nutan , Sharma Vijay L , Sobti Ranbir C , Carlton Jane M , Joshi Hema
Published: January 2012

Malaria is a serious parasitic disease in the developing world, causing high morbidity and mortality. The pathogenesis of malaria is complex, and the clinical presentation of disease ranges from severe and complicated, to mild and uncomplicated, to asymptomatic malaria. Despite a wealth of studies on the clinical severity of disease, asymptomatic malaria infections are still poorly understood. Asymptomatic malaria remains a challenge for malaria control programs as it significantly influences transmission dynamics. A thorough understanding of the interaction between hosts and parasites in the development of different clinical outcomes is required. In this review, the problems and obstacles to the study and control of asymptomatic malaria are discussed. The human and parasite factors associated with differential clinical outcomes are described and the management and treatment strategies for the control of the disease are outlined. Further, the crucial gaps in the knowledge of asymptomatic malaria that should be the focus of future research towards development of more effective malaria control strategies are highlighted.
Sex work involvement among women with long-term opioid injection drug dependence who enter opioid agonist treatment
Authors: Marchand Kirsten , Oviedo-Joekes Eugenia , Guh Daphne , Marsh David C , Brissette Suzanne , Schechter Martin T
Published: January 2012

Background

Substitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Survival sex work, very common among injection drug users, has been associated with poor Opioid Agonist Treatment (OAT) engagement, retention and response. Therefore, this study was undertaken to determine factors associated with engaging in sex work among long-term opioid dependent women receiving OAT.

Methods

Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI), conducted in Vancouver and Montreal (Canada) between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone to injectable diacetylmorphine or injectable hydromorphone, the last two on a double blind basis, over 12 months. A research team, independent of the clinic services, obtained outcome evaluations at baseline and follow-up (3, 6, 9, 12, 18 and 24 months).

Results

A total 53.6% of women reported engaging in sex work in at least one of the research visits. At treatment initiation, women who were younger and had fewer years of education were more likely to be engaged in sex work. The multivariate logistic generalized estimating equation regression analysis determined that psychological symptoms, and high illicit heroin and cocaine use correlated with women's involvement in sex work during the study period.

Conclusions

After entering OAT, women using injection drugs and engaging in sex work represent a particularly vulnerable group showing poorer psychological health and a higher use of heroin and cocaine compared to women not engaging in sex work. These factors must be taken into consideration in the planning and provision of OAT in order to improve treatment outcomes.

Trial Registration

NCT00175357.
The proxy problem anatomized: child-parent disagreement in health related quality of life reports of chronically ill adolescents
Authors: Sattoe Jane NT , van Staa AnneLoes , Moll Henriëtte A ,   On Your Own Feet Research Group
Published: January 2012

Background

Discrepancy between self-reports and parent-proxy reports of adolescent health-related quality of life (HRQoL) has been repeatedly acknowledged in the literature as the proxy problem. However, little is known about the extent and direction of this discrepancy. The purpose of this study is to explore to what extent and in what direction HRQoL self-reports of adolescents with chronic conditions and those of their parents differ.

Methods

A cross-sectional survey was conducted among adolescents suffering from chronic conditions and their parents. Socio-demographic and disease-related characteristics were collected and information about consequences of the chronic condition was assessed. HRQoL was measured with KIDSCREEN-10 and DISABKIDS condition generic measure (DCGM-10). Agreement was analysed through defining a threshold of agreement based on half of the standard deviation of the HRQoL score with the highest variance. Agreement occurred if the difference between adolescent and parent scores was less than or equal to half of the standard deviation. Intra-class correlation coefficients and Bland-Altman plots were also computed. The characteristics associated with direction of disagreement were statistically tested with one-way ANOVA and Chi-square tests.

Results

584 paired HRQoL scores were obtained. Ratings from both adolescents and parents were high, compared to European norm data. Differences between adolescents and parents were statistically significant, yet relatively small. Disagreement existed in both directions: in 24.5% (KIDSCREEN-10) and 16.8% (DCGM-10) of the cases adolescents rated their HRQoL lower than did their parent, while in 32.2% (KIDSCREEN-10) and 31.7% (DCGM-10) of the cases the opposite was true. Adolescent's age, educational level and type of education, parent's educational level, number of hospital admissions and several other disease-related factors influenced direction of disagreement.

Conclusions

In a reasonable proportion of cases the adolescent and parent agreed on the adolescent's HRQoL (43-51% of the cases) and most disagreement tended to be minor. Thus, the proxy problem may be smaller than presented in the literature and its extent may differ per population. As adolescents are expected to become partners in their own health care, it is recommended to focus on adolescents' own perceptions of HRQoL.
Gene silencing of IL-12 in dendritic cells inhibits autoimmune arthritis
Authors: Li Rong , Zheng Xiufen , Popov Igor , Zhang Xusheng , Wang Hongmei , Suzuki Motohiko , De Necochea-Campion Rosalia , French Peter W , Chen Di , Siu Leo , Koos David , Inman Robert D , Min Wei-Ping
Published: January 2012

Background

We have previously demonstrated that immune modulation can be accomplished by administration of gene silenced dendritic cells (DC) using siRNA. In this study, we demonstrate the therapeutic utilization of shRNA-modified DC as an antigen-specific tolerogenic vaccine strategy for autoimmune arthritis.

Methods

A shRNA that specifically targets IL-12 p35 was designed and cloned into a plasmid vectors (IL-12 shRNA). Bone marrow-derived DC from DBA/1 mice were transfected with the IL-12 shRNA construct in vitro. Mice with collagen II (CII)-induced arthritis (CIA) were treated with the modified DCs expressing the shRNA. Recall response and disease progression were assessed.

Results

After gene silencing of IL-12 in DC, DC were shown to selectively inhibit T cell proliferation on recall responses and in an MLR. In murine CIA, we demonstrated that administration of IL-12 shRNA-expressing DC that were pulsed with CII inhibited progression of arthritis. The therapeutic effects were evidenced by decreased clinical scores, inhibition of inflammatory cell infiltration in the joint, and suppression of T cell and B cell responses to CII.

Conclusion

We demonstrate a novel tolerance-inducing protocol for the treatment of autoimmune inflammatory joint disease in which the target antigen is known, utilizing DNA-directed RNA interference.
"Familial" versus "Sporadic" intellectual disability: contribution of common microdeletion and microduplication syndromes
Authors: Rafati Maryam , Seyyedaboutorabi Elaheh , Ghadirzadeh Mohammad R , Heshmati Yaser , Adibi Homeira , Keihanidoust Zarrintaj , Eshraghian Mohammad R , Javadi Gholam Reza , Dastan Jila , Mosavi-Jarrahi Alireza , Hoseini Azadeh , Purhoseini Marzieh , Ghaffari Saeed R
Published: January 2012

Background

Interstitial Microdeletion and Microduplication syndromes have been proposed as a significant cause of sporadic intellectual disability (ID) but the role of such aberrations in familial ID has not yet been investigated. As the balanced chromosomal abnormalities commonly lead to the recurrent ID or multiple congenital anomalies, this study was designed to evaluate whether it was justified to investigate such aberrations in familial ID patients. Three hundred and twenty eight patients from 101 unrelated Iranian families with more than two ID patients in the first-degree relatives, have been investigated. Assessment of a panel of 21 common Microdeletion and Microduplication syndromes (CMMS) was carried out using Multiplex Ligation-Dependent Probe Amplification (MLPA) technique.

Results

Among the families studied, 27.7% had 4-12, 35.6% had 3 and 36.6% had 2 affected individuals in the first-degree relatives. An autosomal dominant inheritance of Williams-Beuren syndrome (WBS) was detected in a family with no clinical suspicion of WBS. The prevalence of CMMS was therefore,0.99%.

Conclusion

This is the first investigation of a panel of CMMS in a large sample set of "familial ID patients". The findings of this study showed the low prevalence of CMMSs in "familial ID" patients in spite of the significant contribution of such aberrations in "sporadic ID" which has a very useful practical impact by avoiding unnecessary diagnostic tests in "familial ID" patients.
From baconian to popperian neuroscience
Authors: Gamez David
Published: January 2012

The development of neuroscience over the past 50 years has some similarities with the development of physics in the 17th century. Towards the beginning of that century, Bacon promoted the systematic gathering of experimental data and the induction of scientific truth; towards the end, Newton expressed his principles of gravitation and motion in a concise set of mathematical equations that made precise falsifiable predictions. This paper expresses the opinion that as neuroscience comes of age, it needs to move away from amassing large quantities of data about the brain, and adopt a popperian model in which theories are developed that can make strong falsifiable predictions and guide future experimental work.
A profile of immune response to herpesvirus is associated with radiographic joint damage in rheumatoid arthritis
Authors: Davis John M , Knutson Keith L , Skinner John A , Strausbauch Michael A , Crowson Cynthia S , Therneau Terry M , Wettstein Peter J , Matteson Eric L , Gabriel Sherine E
Published: January 2012

Introduction

Progression of joint damage despite appropriate therapy remains a significant problem for patients with rheumatoid arthritis (RA). This study was undertaken to identify profiles of immune response that correlate with radiographic joint damage as a first step toward the discovery of new pathogenic mechanisms of joint destruction in RA.

Methods

The study included 58 patients with RA and 15 healthy controls. The profiles of cytokine release from peripheral blood mononuclear cells (PBMC) in response to stimulation for 48 hours with one of six stimuli, or in media alone, were measured. Immune response profiles identified for each stimulus were correlated with radiographic joint damage as defined by the Sharp-van der Heijde score (SHS), before and after multivariable adjustment. For profiles correlated with the SHS, the distributions of individual cytokines were evaluated in patients according to the severity of joint damage and compared to healthy controls.

Results

The immune response profile for cytomegalovirus (CMV)/Epstein-Barr virus (EBV) stimulation was correlated with both the SHS total and erosion scores (r = 0.31, P = 0.018 and r = 0.33, P = 0.011, respectively). After adjusting for age, sex, disease duration, autoantibody status, CMV/EBV serological status, current disease activity, disability and treatments, the correlation of the CMV/EBV immune response and the SHS erosion score became stronger (r = 0.43, P < 0.003). The CMV/EBV immune response correlated with CMV IgG (r = 0.44, P < 0.001), but not with EBV IgG. The most important cytokines for the CMV/EBV immune response profile were IFN-γ, IL-2, IL-4, IL-5, IL-13 and IL-17A, all of which are associated with T-cell immunity. Both the summary immune response score and the individual responses of IFN-γ and IL-13 to CMV/EBV stimulation were associated with greater joint damage.

Conclusions

A profile of immune response to purified CMV/EBV lysates is associated with radiographic joint damage. The correlation of this immune response to CMV serology implies possible involvement of latent CMV infection. Therefore, the findings suggest that the immune response to latent CMV infection could play a fundamental role in the progression of inflammation and structural joint damage in patients with RA.
MetaMerge: scaling up genome-scale metabolic reconstructions with application to Mycobacterium tuberculosis
Authors: Chindelevitch Leonid , Stanley Sarah , Hung Deborah , Regev Aviv , Berger Bonnie
Published: January 2012

Reconstructed models of metabolic networks are widely used for studying metabolism in various organisms. Many different reconstructions of the same organism often exist concurrently, forcing researchers to choose one of them at the exclusion of the others. We describe MetaMerge, an algorithm for semi-automatically reconciling a pair of existing metabolic network reconstructions into a single metabolic network model. We use MetaMerge to combine two published metabolic networks for Mycobacterium tuberculosis into a single network, which allows many reactions that could not be active in the individual models to become active, and predicts essential genes with a higher positive predictive value.
Recurrence and Survival After Random Assignment to Laparoscopy Versus Laparotomy for Comprehensive Surgical Staging of Uterine Cancer: Gynecologic Oncology Group LAP2 Study
Authors: Walker Joan L. , Piedmonte Marion R. , Spirtos Nick M. , Eisenkop Scott M. , Schlaerth John B. , Mannel Robert S. , Barakat Richard , Pearl Michael L. , Sharma Sudarshan K.
Published: January 2012

Purpose

The primary objective was to establish noninferiority of laparoscopy compared with laparotomy for recurrence after surgical staging of uterine cancer.

Patients and Methods

Patients with clinical stages I to IIA disease were randomly allocated (two to one) to laparoscopy (n = 1,696) versus laparotomy (n = 920) for hysterectomy, salpingo-oophorectomy, pelvic cytology, and pelvic and para-aortic lymphadenectomy. The primary study end point was noninferiority of recurrence-free interval defined as no more than a 40% increase in the risk of recurrence with laparoscopy compared with laparotomy.

Results

With a median follow-up time of 59 months for 2,181 patients still alive, there were 309 recurrences (210 laparoscopy; 99 laparotomy) and 350 deaths (229 laparoscopy; 121 laparotomy). The estimated hazard ratio for laparoscopy relative to laparotomy was 1.14 (90% lower bound, 0.92; 95% upper bound, 1.46), falling short of the protocol-specified definition of noninferiority. However, the actual recurrence rates were substantially lower than anticipated, resulting in an estimated 3-year recurrence rate of 11.4% with laparoscopy and 10.2% with laparotomy, or a difference of 1.14% (90% lower bound, −1.28; 95% upper bound, 4.0). The estimated 5-year overall survival was almost identical in both arms at 89.8%.

Conclusion

This study previously reported that laparoscopic surgical management of uterine cancer is superior for short-term safety and length-of-stay end points. The potential for increased risk of cancer recurrence with laparoscopy versus laparotomy was quantified and found to be small, providing accurate information for decision making for women with uterine cancer.
Compassionate Conversions: Gower’s Confessio Amantis and the Problem of Envy
Authors: Rosenfeld Jessica
Published: January 2012

Medieval penitential writings often proclaim envy to be the “worst” sin because it is committed without pleasure. Envy thus poses a problem for traditional moral frameworks that suggest sin can be avoided by turning one’s desire away from earthly pleasures — envious desire is not addressed by this solution. Unlike the other “deadly” sins, envy’s economy of pleasure and pain is not object-oriented, but other-oriented. This essay examines John Gower’s Confessio Amantis, arguing that its focus on envy inspires a reorientation of penitential morality around the pains and pleasures inherent in one’s relationship to one’s neighbor. Gower’s tales explore the proximity of envy and compassion, asking crucial questions about how envious identification can be turned instead into compassionate likeness, and commenting on the larger project of exemplarity and mimetic narrative.
Pontomedullary lacerations in pedestrians: an autopsy study
Authors: Živković Vladimir , Nikolić Slobodan , Strajina Veljko , Djonić Danijela , Babić Dragan , Djurić Marija
Published: January 2012

It is common that injuries to the head are among the most frequent injuries found in pedestrian accidents, and can constitute a serious, if not fatal, threat. Brainstem lesions have only occasionally been reported in pedestrian injuries. The aim of this study has been to determine the frequency of brainstem pontomedullary lacerations (PMLs) among fatally injured pedestrians, the frequency of concomitant cranial, facial and cervical spine injuries in such cases, as well as to establish their possible underlying mechanism. In this work, PML was present in a significant number of fatally injured pedestrians from a sample of 50 out of 360 cases with head injuries (14%). When observed alone, the most frequent head impact areas were the chin, lateral and frontal ( χ2 = 14.200, df = 4, P = 0.007) in the subgroup with PML. Hinge fractures were most often seen in this subgroup (25 cases), followed by the absence of skull base fractures ( χ2 = 26.320, df = 3, P < 0.01). There are several possible mechanisms of PML in these cases. Impact to the chin, with or without a skull base fracture, could lead to this fatal injury due to impact force transmission. Additionally, lateral head impacts, the most frequent in pedestrians, with subsequent hinge fractures, PML and fronto-posterior hyperextension of the head that is associated with upper-spine fractures, may be possible mechanisms of brainstem injury in fatally injured pedestrians.
Retrospective analysis of anaesthesia-related deaths during a 12-year period: looking at the data from a forensic point of view
Authors: Turillazzi E , Bello S , Bonsignore A , Neri M , Riezzo I , Fineschi V
Published: January 2012

Anaesthesia-related death is one of the most complex events to be studied in forensic pathology because of its rarity and its doubtful presentation. Particularly, the difficulties in assessing the cause of deaths in such circumstances are underlined. A scale must be considered in order to determine the causal role of anaesthesia in the process leading to death. Indeed, beyond deaths exclusively explained by anaesthetic care, there are deaths that are not anaesthesia-related and deaths explained by surgery and co-morbidities in which the role of anaesthetic care has to be carefully investigated. A retrospective analysis of 3138 autopsies is presented with the aim of better understanding the patho-physiological process of anaesthesia-related mortality and to determine the causal role of anaesthesiological care in the process leading to death, thus assessing the real incidence of deaths due to anaesthesia (0.16%). In the present study, the number of deaths generically anaesthesia-related (33 cases) accounts for 2.06% of autopsies due to medical malpractice claims and 1.05% of all autopsies. The number of deaths totally related to anaesthesic care is rather low with 0.32% of autopsies due to medical malpractice claims and 0.16% of all autopsies. Anaesthesia-related deaths were due to lack of or delay in intubation (2 cases), acute cardio-respiratory failure (2 cases) and anaesthetic-induced hepatotoxicity (1 case). The importance of a careful forensic investigation (clinical and familial history, medical records, complete autopsy and toxicology), which can lead to a clear understanding of anaesthesia-related deaths, is also stressed.
Improved prediction of RNA tertiary structure with insights into native state dynamics
Authors: Bida John Paul , Maher L. James
Published: January 2012

The importance of RNA tertiary structure is evident from the growing number of published high resolution NMR and X-ray crystallographic structures of RNA molecules. These structures provide insights into function and create a knowledge base that is leveraged by programs such as Assemble, ModeRNA, RNABuilder, NAST, FARNA, Mc-Sym, RNA2D3D, and iFoldRNA for tertiary structure prediction and design. While these methods sample native-like RNA structures during simulations, all struggle to capture the native RNA conformation after scoring. We propose RSIM, an improved RNA fragment assembly method that preserves RNA global secondary structure while sampling conformations. This approach enhances the quality of predicted RNA tertiary structure, provides insights into the native state dynamics, and generates a powerful visualization of the RNA conformational space. RSIM is available for download from http://www.github.com/jpbida/rsim.
Solution-phase synthesis of bowl- and basket-shaped fullerene fragments via benzannulated enyne–allenes
Authors: Wen Bo , Wang Kung K.
Published: January 2012

Benzannulated enyne-allenes bearing an aryl substituent at both the alkynyl and allenyl termini are excellent precursors of 5-aryl-11H-benzo[b]fluorenyl derivatives having the carbon frameworks of fullerene fragments. The mildness of the reaction conditions and the availability of several synthetic methods for benzannulated enyne-allenes allow the design of new synthetic pathways leading to bowl- and basket-shaped fullerene fragments. Specifically, a bowl-shaped C28H18 hydrocarbon bearing a 27-carbon framework of C60 and a basket-shaped C56H40 hydrocarbon bearing a 54-carbon framework of C60 were synthesized. The interior 30-carbon core of the C56H40 hydrocarbon can be regarded as a partially hydrogenated [5,5]circulene, a C30H12 semibuckminsterfullerene. In addition, a basket-shaped C56H38 hydrocarbon was also constructed to serve as a precursor toward an end-cap template for (6,6) carbon nanotubes.
Use of Levonorgestrel Emergency Contraception In Utah: Is It More than “Plan B”?
Authors: Melton Lindsay , Stanford Joseph B. , Dewitt M. Jann
Published: January 2012

CONTEXT:

It is important to understand why some women use levonorgestrel emergency contraceptive pills repeatedly, because the method is not intended for repeated use, and current evidence suggests that it is approximately 77% effective at preventing pregnancy.

METHODS:

An anonymous patient survey of 1,040 women aged 18–29 purchasing levonorgestrel at Planned Parenthood clinics in Utah was conducted during a 4–6‐week period in 2007. Chi‐square tests and analyses of variance were used to examine associations between selected characteristics and level of levonorgestrel use. Logistic regression was used to assess characteristics independently associated with repeated use.

RESULTS:

Twenty‐nine percent of participants had used levonorgestrel more than twice in the prior year. Fifty‐eight percent believed that levonorgestrel is at least 90% effective in protecting against pregnancy; 16% believed that it is 100% effective. In univariate analyses, lifetime number of partners, currently having multiple partners, substance use at last intercourse and perceived effectiveness of levonorgestrel were positively associated with repeated levonorgestrel use in the previous year. The measure most strongly associated with repeated levonorgestrel use in multivariate analyses was perceived effectiveness: Women who believed that the method is 90–99% or 100% effective in preventing pregnancy had greater odds of repeated use than those who believed it is 75–89% effective (odds ratios, 1.8 each).

CONCLUSION:

Women who repeatedly use levonorgestrel may have an inflated perception of its effectiveness. Future research, including qualitative research, may help clarify factors that lead to inflated perceptions of effectiveness.
An On-Line Near-Infrared (NIR) Transmission Method for Determining Depth Profiles of Fatty Acid Composition and Iodine Value in Porcine Adipose Fat Tissue
Authors: Sørensen Klavs Martin , Petersen Henrik , Engelsen Søren Balling
Published: January 2012

The present work describes a measurement method using spatially resolved near-infrared (NIR) spectroscopy to determine porcine carcass fat quality as a function of the distance to the skin by estimating its iodine value (IV). The new method is capable of performing on-line carcass grading at full production speed (approximately 1000 carcasses per hour). The method is demonstrated in an experiment where 35 carcasses were sampled at an abattoir, selected from three feeding groups. The NIR transmission instrument was applied on the loin of each carcass, and a parallel reference sample was removed and processed into 1.8 mm thick disks, representing a depth-of-fat profile from the loin. The disks were analyzed for fatty acid composition using gas chromatography (GC) and for IV. A principal component analysis (PCA) of the obtained GC reference values clearly showed that the feeding regimes can be differentiated. Using interval partial least squares (iPLS) regression, a model was produced that can predict the IV of the fat at a given measured depth with a root mean square error of cross-validation (RMSECV) of 1.44. The results show how the IV varies as a function of feeding regime and as a function of fat depth. The maximum variation found within a single depth profile was 10.1 IV from the skin to the innermost part of the fat layers. In the sample material investigated the average span in IV between the average values of the two porcine backfat layers was 6.4 IV (the maximum difference was 8.6 IV). The new method can provide the abattoir with new chemical information about fat quality and production quality that will open new possibilities of meat/carcass grading and product development.
Distinct Roles for Specific Leptin Receptor Signals in the Development of Hypothalamic Feeding Circuits
Authors: Bouret Sebastien G. , Bates Sarah H. , Chen Stephen , Myers Martin G. , Simerly Richard B.
Published: January 2012

Circulating hormones influence multiple aspects of hypothalamic development and play a role in directing formation of neural circuits. Leptin is secreted by adipocytes and functions as a key developmental signal that promotes axon outgrowth from the arcuate nucleus (ARH) during a discrete developmental critical period. To determine the cellular mechanisms by which leptin impacts development of hypothalamic circuits, we examined roles for leptin receptor (LepRb) signals in neonatal mice. LepRb, ERK, and STAT3 signaling were required for leptin-stimulated neurite outgrowth from ARH explantsin vitro. Neonatal mice with disrupted LepRb→ERK signaling displayed impaired ARH projections but were able to compensate by adulthood. LepRb→STAT3 signaling also plays a role in early circuit formation and controls the ultimate architecture of POMC, but not AgRP, projections. Thus, the developmental actions of leptin on feeding circuits are dependent on LepRb, and distinct signaling pathways are responsible for directing formation of NPY and POMC projections.
Similar Intracellular Ca2+Requirements for Inactivation and Facilitation of Voltage-Gated Ca2+Channels in a Glutamatergic Mammalian Nerve Terminal
Authors: Lin Kun-Han , Erazo-Fischer Emilio , Taschenberger Holger
Published: January 2012

Voltage-gated Ca2+channels (VGCCs) of the P/Q-type, which are expressed at a majority of mammalian nerve terminals, show two types of Ca2+-dependent feedback regulation—inactivation (CDI) and facilitation (CDF). Because of the nonlinear relationship between Ca2+influx and transmitter release, CDI and CDF are powerful regulators of synaptic strength. To what extent VGCCs inactivate or facilitate during spike trains depends on the dynamics of free Ca2+([Ca2+]i) and the Ca2+sensitivity of CDI and CDF, which has not been determined in nerve terminals. In this report, we took advantage of the large size of a rat auditory glutamatergic synapse—the calyx of Held—and combined voltage-clamp recordings of presynaptic Ca2+currents (ICa(V)) with UV-light flash-induced Ca2+uncaging and presynaptic Ca2+imaging to study the Ca2+requirements for CDI and CDF.

We find that nearly half of the presynaptic VGCCs inactivate during 100 ms voltage steps and require several seconds to recover. This inactivation is caused neither by depletion of Ca2+ions from the synaptic cleft nor by metabotropic feedback inhibition, because it is resistant to blockade of metabotropic and ionotropic glutamate receptors. Facilitation ofICa(V)induced by repetitive depolarizations or preconditioning voltage steps decays within tens of milliseconds. Since Ca2+buffers only weakly affect CDI and CDF, we conclude that the Ca2+sensors are closely associated with the channel. CDI and CDF can be induced by intracellular photo release of Ca2+resulting in [Ca2+]ielevations in the low micromolar range, implying a surprisingly high affinity of the Ca2+sensors.
The Amplitude and Timing of the BOLD Signal Reflects the Relationship between Local Field Potential Power at Different Frequencies
Authors: Magri Cesare , Schridde Ulrich , Murayama Yusuke , Panzeri Stefano , Logothetis Nikos K.
Published: January 2012

There is growing evidence that several components of the mass neural activity contributing to the local field potential (LFP) can be partly separated by decomposing the LFP into nonoverlapping frequency bands. Although the blood oxygen level-dependent (BOLD) signal has been found to correlate preferentially with specific frequency bands of the LFP, it is still unclear whether the BOLD signal relates to the activity expressed by each LFP band independently of the others or if, instead, it also reflects specific relationships among different bands. We investigated these issues by recording, simultaneously and with high spatiotemporal resolution, BOLD signal and LFP during spontaneous activity in early visual cortices of anesthetized monkeys (Macaca mulatta). We used information theory to characterize the statistical dependency between BOLD and LFP. We found that the alpha (8–12 Hz), beta (18–30 Hz), and gamma (40–100 Hz) LFP bands were informative about the BOLD signal. In agreement with previous studies, gamma was the most informative band. Both increases and decreases in BOLD signal reliably followed increases and decreases in gamma power. However, both alpha and beta power signals carried information about BOLD that was largely complementary to that carried by gamma power. In particular, the relationship between alpha and gamma power was reflected in the amplitude of the BOLD signal, while the relationship between beta and gamma bands was reflected in the latency of BOLD with respect to significant changes in gamma power. These results lay the basis for identifying contributions of different neural pathways to cortical processing using fMRI.
Concentration-Dependent Requirement for Local Protein Synthesis in Motor Neuron Subtype-Specific Response to Axon Guidance Cues
Authors: Nédelec Stéphane , Peljto Mirza , Shi Peng , Amoroso Mackenzie W. , Kam Lance C. , Wichterle Hynek
Published: January 2012

Formation of functional motor circuits relies on the ability of distinct spinal motor neuron subtypes to project their axons with high precision to appropriate muscle targets. While guidance cues contributing to motor axon pathfinding have been identified, the intracellular pathways underlying subtype-specific responses to these cues remain poorly understood. In particular, it remains controversial whether responses to axon guidance cues depend on axonal protein synthesis. Using a growth cone collapse assay, we demonstrate that mouse embryonic stem cell-derived spinal motor neurons (ES-MNs) respond to ephrin-A5, Sema3f, and Sema3a in a concentration-dependent manner. At low doses, ES-MNs exhibit segmental or subtype-specific responses, while this selectivity is lost at higher concentrations. Response to high doses of semaphorins and to all doses of ephrin-A5 is protein synthesis independent. In contrast, using microfluidic devices and stripe assays, we show that growth cone collapse and guidance at low concentrations of semaphorins rely on local protein synthesis in the axonal compartment. Similar bimodal response to low and high concentrations of guidance cues is observed in human ES-MNs, pointing to a general mechanism by which neurons increase their repertoire of responses to the limited set of guidance cues involved in neural circuit formation.
Event-Related Nociceptive Arousal Enhances Memory Consolidation for Neutral Scenes
Authors: Schwarze Ulrike , Bingel Ulrike , Sommer Tobias
Published: January 2012

The superior memory for emotional events has been attributed to the beneficial effects of noradrenaline released into the amygdala attributable to arousal. Noradrenaline mediates the effects of different hormones and neurotransmitters, including adrenal stress hormones on consolidation (McGaugh, 2004; Roozendaal et al., 2009). The majority of human fMRI studies of the enhancement of emotional memories contrasted successful encoding of emotionally arousing and neutral stimuli (LaBar and Cabeza, 2006; Murty et al., 2010). Recently, it was highlighted that emotional stimuli elicit not only arousal but also intensify cognitive processes that contribute to the enhanced memory. In particular, the enhanced use of selective attention as well as the greater distinctiveness and semantic relatedness of emotional stimuli influence memory formation (Talmi et al., 2007a). The present study aimed to explore the effects of arousal on memory formation independent of these cognitive factors in an event-related manner. Arousal was induced by the application of a nociceptive stimulus briefly after the presentation of neutral scenes. The results show a purely arousal-driven memory enhancement for the neutral scenes that differs in critical aspects from the superior memory for emotional stimuli. In particular, the enhancement was only evident after consolidation and exclusively based on an increase in item familiarity but not recollection. Moreover, successful memory formation for stimuli followed by arousal was correlated with activity in the parahippocampal cortex but not the amygdala, as is the case for emotional stimuli.
α4* Nicotinic Acetylcholine Receptors Modulate Experience-Based Cortical Depression in the Adult Mouse Somatosensory Cortex
Authors: Brown Craig E. , Sweetnam Danielle , Beange Maddie , Nahirney Patrick C. , Nashmi Raad
Published: January 2012

The molecular mechanisms that mediate experience-based changes in the function of the cerebral cortex, particularly in the adult animal, are poorly understood. Here we show usingin vivovoltage-sensitive dye imaging, that whisker trimming leads to depression of whisker-evoked sensory responses in primary, secondary and associative somatosensory cortical regions. Given the importance of cholinergic neurotransmission in cognitive and sensory functions, we examined whether α4-containing (α4*) nicotinic acetylcholine receptors (nAChRs) mediate cortical depression. Using knock-in mice that express YFP-tagged α4 nAChRs subunits, we show that whisker trimming selectively increased the number α4*-YFP nAChRs in layer 4 of deprived barrel columns within 24 h, which persisted until whiskers regrew. Confocal and electron microscopy revealed that these receptors were preferentially increased on the cell bodies of GABAergic neurons. To directly link these receptors with functional cortical depression, we show that depression could be induced in normal mice by topical application or micro-injection of α4* nAChR agonist in the somatosensory cortex. Furthermore, cortical depression could be blocked after whisker trimming with chronic infusions of an α4* nAChR antagonist. Collectively, these results uncover a new role for α4* nAChRs in regulating rapid changes in the functional responsiveness of the adult somatosensory cortex.
NP1 Regulates Neuronal Activity-Dependent Accumulation of BAX in Mitochondria and Mitochondrial Dynamics
Authors: Clayton Kevin B. , Podlesniy Petar , Figueiro-Silva Joana , López-Doménech Guillermo , Benitez Lluis , Enguita Marta , Abad Maria A. , Soriano Eduardo , Trullas Ramon
Published: January 2012

In cultured cerebellar granule neurons, low neuronal activity triggers the intrinsic program of apoptosis, which requires protein synthesis-dependent BAX translocation to mitochondria, a process that may underlie neuronal damage in neurodegeneration. However, the mechanisms that link neuronal activity with the induction of the mitochondrial program of apoptosis remain unclear. Neuronal pentraxin 1 (NP1) is a pro-apoptotic protein induced by low neuronal activity that is increased in damaged neurites in Alzheimer's disease-affected brains. Here we report that NP1 facilitates the accumulation of BAX in mitochondria and regulates mitochondrial dynamics during apoptosis in rat and mouse cerebellar granule neurons in culture. Reduction of neuronal activity increases NP1 protein levels in mitochondria and contributes to mitochondrial fragmentation in aBax-dependent manner. In addition, NP1 is involved in mitochondrial transport in healthy neurons. These results show that NP1 is targeted to mitochondria acting upstream of BAX and uncover a novel function for NP1 in the regulation of mitochondrial dynamics and trafficking during apoptotic neurodegeneration.
Human Motor Plasticity Induced by Mirror Visual Feedback
Authors: Nojima Ippei , Mima Tatsuya , Koganemaru Satoko , Thabit Mohamed Nasreldin , Fukuyama Hidenao , Kawamata Toshio
Published: January 2012

The clinical use of mirror visual feedback (MVF) was initially introduced to alleviate phantom pain, and has since been applied to the improvement of hemiparesis following stroke. However, it is not known whether MVF can restore motor function by producing plastic changes in the human primary motor cortex (M1). Here, we used transcranial magnetic stimulation to test whether M1 plasticity is a physiological substrate of MVF-induced motor behavioral improvement. MVF intervention in normal volunteers using a mirror box improved motor behavior and enhanced excitatory functions of the M1. Moreover, behavioral and physiological measures of MVF-induced changes were positively correlated with each other. Improved motor performance occurred after observation of a simple action, but not after repetitive motor training of the nontarget hand without MVF, suggesting the crucial importance of visual feedback. The beneficial effects of MVF were disrupted by continuous theta burst stimulation (cTBS) over the M1, but not the control site in the occipital cortex. However, MVF following cTBS could further improve the motor functions. Our findings indicate that M1 plasticity, especially in its excitatory connections, is an essential component of MVF-based therapies.
Early Exposure to Alcohol Leads to Permanent Impairment of Dendritic Excitability in Neocortical Pyramidal Neurons
Authors: Granato Alberto , Palmer Lucy M. , De Giorgio Andrea , Tavian Daniela , Larkum Matthew E.
Published: January 2012

Exposure to alcoholin uterois a well known cause of mental retardation in humans. Using experimental models of fetal alcohol spectrum disorder, it has been demonstrated that cortical pyramidal neurons and their projections are profoundly and permanently impaired. Yet, how the functional features of these cells are modified and how such modifications impact cognitive processes is still unknown. To address this, we studied the intrinsic electrophysiological properties of pyramidal neurons in young adult rats (P30–P60) exposed to ethanol inhalation during the first week of postnatal life (P2–P6). Dual whole-cell recordings from the soma and distal apical dendrites were performed and, following the injection of depolarizing current into the dendrites, layer 5 neurons from ethanol-treated (Et) animals displayed a lower number and a shorter duration of dendritic spikes, attributable to a downregulation of calcium electrogenesis. As a consequence, the mean number of action potentials recorded at the soma after dendritic current injection was also lower in Et animals. No significant differences between Et and controls were observed in the firing pattern elicited in layer 5 neurons by steps of depolarizing somatic current, even though the firing rate was significantly lower in Et animals. The firing pattern and the firing rate of layer 2/3 neurons were not affected by alcohol exposure.