bluuebunny/crossref_metadata_2025 huggingface dataset:
Alpha Meals
Authors: Fernandes Myra A. , Miller Ethan , Michela John L.
Published: May 2013

Past research suggests that our ability to recall information increases when atypical items are presented within otherwise homogeneous sets. We investigated whether this effect applied to performance on practical, everyday tasks. In a computer-simulated restaurant scenario, participants acted as virtual servers, delivering “plates of food orders” to tables set up in different “rooms.” Plate destination was communicated using either a distinctive alphanumeric code or a homogeneous numeric code, both of which indicated the room and table number for delivery of food orders. We examined accuracy of plate delivery when two (low load) or three (high load) coded assignments were given per delivery trial. As expected, performance declined from the low- to high-load condition. Importantly, performance declined less with alphanumeric compared with all-numeric communication of assignments. Results suggest that increasing the distinctiveness of assignments, by using alphanumeric codes, can boost performance in real-life situations to significantly improve memory-related task performance, particularly when cognitive load is taxed.
Variations in African American and Non-Hispanic White Children’s Health Care Utilization
Authors: Ashiabi Godwin S.
Published: May 2013

A multigroup structural equation model was used to investigate the processes underlying health care use between Black and White children. Data from the 2003 National Survey of Children’s Health (NSCH), a computer-assisted telephone survey, were used. The sample for this research consisted of 28,064 Black and White children, ages 4 to 11 years, drawn from the larger pool of children whose families participated in the survey. Results showed that the processes underlying health care use were similar for Blacks and Whites; however, there were some differences in factor loadings between Blacks and Whites. Furthermore, there were differences between Blacks and Whites in the effects of (a) family economic resources on health problems, (b) health problems and access to care on parental distress, and (c) access to care and health problems on prevention- and curative-based use. No interaction effects were found for Blacks and Whites in the associations between (a) parental distress, and satisfaction with physician interaction and health care usage, and (b) satisfaction with physician interactions and health care utilization.
HIV Presenting as Young-Onset Dementia
Authors: Verma Rohit , Anand Kuljeet Singh
Published: May 2013

With the advent of retroviral therapies, the incidence of severe dementia associated with HIV has been reduced, although minor neurocognitive impairment is being increasingly recognized in the course of illness. We report a case of a young woman presenting with HIV-associated dementia and raise awareness of its presentation in young age and as the first presenting symptom.
Falls in HIV-Infected Patients
Authors: Ruiz Marco Andres , Reske Tom , Cefalu Charles , Estrada John
Published: May 2013

Background:

Falls is a common geriatric syndrome that has not been well characterized in HIV-infected populations.

Methods:

We retrospectively reviewed our database and identified patients who fell over the last 12 months.

Results:

Thirty-two patients were identified (incidence rate of 16 × 1000 patients per year). Twenty-five percent were female and 75% male. Sixty-seven percent were African American with 33% Caucasians. Average age was 48.19, number of years with HIV infection on average was 9.38 years, mean CD4 count 347.2 cell/mm3, mean HIV viral load was 31 379 copies/mL. The average number of medications was 8.7 with a mean of 3.48 comorbidities. The mean vitamin D level was 27.20. Sixty-two percent of patients were compliant with antiretroviral therapy. Univariate and multivariate analysis showed that number of medications (< .005 medications; P < .005), more than 3 comorbidities ( P < .005), and noncompliance ( P < .001) were related to falls in this population.

Conclusion:

Falls is a common geriatric syndrome. Associated risk factors in our cohort included number of medications, more than 3 comorbidities, and noncompliance. Larger studies are needed to properly characterize this geriatric syndrome in HIV-infected patients. As HIV-infected populations age, a shift into a more comprehensive geriatrics care including fall risk evaluation may be needed.
The Efficacy of a Computerized Assessment of Medication Adherence in Active Substance Users
Authors: Newville Howard , Sorensen James L.
Published: May 2013

Background:

Self-reports of medication adherence are subject to recall errors and social desirability bias. The visual analogue scale (VAS) is a brief measure and minimally burdensome. Its accuracy among substance users needs confirmation.

Methods:

We administered the VAS on an audio computer-assisted self-interview (ACASI) to 102 HIV-positive active substance users. Viral load (VL) was obtained via chart review. Cohen κ assessed the overall agreement between VL suppression and adherence, and a receiver–operator characteristic (ROC) curve assessed the diagnostic performance.

Results:

The VAS estimates of adherence correlated with VL. Various cutoffs for adherence were associated with VL suppression, demonstrating fair to moderate agreement through κ. Area under the curve (AUC) demonstrated that the ACASI-administered VAS strongly predicted VL suppression (AUC = 0.79).

Discussion:

The VAS administered by ACASI is viable for measuring highly active antiretroviral therapy (HAART) adherence among substance users. Its benefits as a screening instrument may make it useful for both clinical and research purposes.
Tyrosine kinase inhibitors impair B-cell immune responses in CML through off-target inhibition of kinases important for cell signaling
Authors: de Lavallade Hugues , Khoder Ahmad , Hart Melanie , Sarvaria Anushruti , Sekine Takuya , Alsuliman Abdullah , Mielke Stephan , Bazeos Alexandra , Stringaris Kate , Ali Sara , Milojkovic Dragana , Foroni Letizia , Chaidos Aristeidis , Cooper Nichola , Gabriel Ian , Apperley Jane , Belsey Sarah , Flanagan Robert J. , Goldman John , Shpall Elizabeth J. , Kelleher Peter , Marin David , Rezvani Katayoun
Published: May 2013

Key Points

TKIs impair B-cell immune responses in CML through off-target inhibition of kinases important for B-cell signaling. Our results call for close monitoring of patients on TKI to assess the long-term impact of impaired B-cell function.
Gene-centric association study of acute chest syndrome and painful crisis in sickle cell disease patients
Authors: Galarneau Geneviève , Coady Sean , Garrett Melanie E. , Jeffries Neal , Puggal Mona , Paltoo Dina , Soldano Karen , Guasch Antonio , Ashley-Koch Allison E. , Telen Marilyn J. , Kutlar Abdullah , Lettre Guillaume , Papanicolaou George J.
Published: May 2013

Key Points

Using genome-wide association study, we found the first replicated genetic association with acute chest syndrome in sickle cell disease patients. The locus identified includes COMMD7, a gene highly expressed in the lung that interacts with NFκB to control inflammatory responses.
Heterogeneity of young and aged murine hematopoietic stem cells revealed by quantitative clonal analysis using cellular barcoding
Authors: Verovskaya Evgenia , Broekhuis Mathilde J. C. , Zwart Erik , Ritsema Martha , van Os Ronald , de Haan Gerald , Bystrykh Leonid V.
Published: May 2013

Key Points

Quantitative clonal analysis demonstrates directional changes in contributions of stem cells to blood. The pool of aged hematopoietic stem cells is comprised of many, but small clones, while young stem cells are less numerous, but more potent.
Accounting for immunoprecipitation efficiencies in the statistical analysis of ChIP-seq data
Authors: Bao Yanchun , Vinciotti Veronica , Wit Ernst , ’t Hoen Peter AC
Published: May 2013

Background

ImmunoPrecipitation (IP) efficiencies may vary largely between different antibodies and between repeated experiments with the same antibody. These differences have a large impact on the quality of ChIP-seq data: a more efficient experiment will necessarily lead to a higher signal to background ratio, and therefore to an apparent larger number of enriched regions, compared to a less efficient experiment. In this paper, we show how IP efficiencies can be explicitly accounted for in the joint statistical modelling of ChIP-seq data.

Results

We fit a latent mixture model to eight experiments on two proteins, from two laboratories where different antibodies are used for the two proteins. We use the model parameters to estimate the efficiencies of individual experiments, and find that these are clearly different for the different laboratories, and amongst technical replicates from the same lab. When we account for ChIP efficiency, we find more regions bound in the more efficient experiments than in the less efficient ones, at the same false discovery rate. A priori knowledge of the same number of binding sites across experiments can also be included in the model for a more robust detection of differentially bound regions among two different proteins.

Conclusions

We propose a statistical model for the detection of enriched and differentially bound regions from multiple ChIP-seq data sets. The framework that we present accounts explicitly for IP efficiencies in ChIP-seq data, and allows to model jointly, rather than individually, replicates and experiments from different proteins, leading to more robust biological conclusions.
High Resolution Melting analysis as a rapid and efficient method of screening for small mutations in the STK11gene in patients with Peutz-Jeghers syndrome
Authors: Borun Pawel , Bartkowiak Anna , Banasiewicz Tomasz , Nedoszytko Boguslaw , Nowakowska Dorota , Teisseyre Mikolaj , Limon Janusz , Lubinski Jan , Kubaszewski Lukasz , Walkowiak Jaroslaw , Czkwianianc Elzbieta , Siolek Monika , Kedzia Agnieszka , Krokowicz Piotr , Cichy Wojciech , Plawski Andrzej
Published: May 2013

Background

Peutz-Jeghers syndrome (PJS) is a rare hereditary syndrome characterized by the occurrence of hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation and increased risk of cancer in multiple internal organs. Depending on the studied population, its incidence has been estimated to range from 1:200 000 even up to 1:50 000 births. Being an autosomal disease, PJS is caused in most cases by mutations in the STK11 gene.

Methods

The majority of causative DNA changes identified in patients with PJS are small mutations and, therefore, developing a method of their detection is a key aspect in the advancement of genetic diagnostics of PJS patients. We designed 13 pairs of primers, which amplify at the same temperature and enable examination of all coding exons of the STK11 gene by the HRM analysis.

Results

In our group of 41 families with PJS small mutations of the STK11 gene were detected in 22 families (54%). In the remaining cases all of the coding exons were sequenced. However, this has not allowed to detect any additional mutations.

Conclusions

The developed methodology is a rapid and cost-effective screening tool for small mutations in PJS patients and makes it possible to detect all the STK11 gene sequence changes occurring in this group.
A novel model of adenine-induced tubulointerstitial nephropathy in mice
Authors: Jia Ting , Olauson Hannes , Lindberg Karolina , Amin Risul , Edvardsson Karin , Lindholm Bengt , Andersson Göran , Wernerson Annika , Sabbagh Yves , Schiavi Susan , Larsson Tobias E
Published: May 2013

Background

In vivo models of uremia are important tools to study numerous aspects of acute and chronic kidney disease. Mouse models are pivotal because most genetically engineered animal models are mice, which allow dissecting the impact of selected target genes in renal failure. Adenine-based protocols to induce renal failure are available in rats, but have not been adapted in mice due to their reluctance to consume adenine. In the current paper we developed a novel method for induction of renal failure through dietary delivery of adenine mixed in a casein-based diet.

Results

After an induction phase, a stable model of renal impairment was obtained (target urea range 80–100 mg/dL), mimicking several aspects of chronic kidney disease - mineral and bone disorder including secondary hyperparathyroidism, bone abnormalities and pathological elevation of FGF23. No deaths occurred and the level of uremia was adaptable through adjustments of the adenine content, providing significant advantages compared to existing models. In an 8-week proof-of-concept study, renal histology showed mainly a tubulointerstitial damage with infiltrating leukocytes, interstitial edema and widening of the Bownman's space. Fibrosis was present in most animals as defined by histology and gene expression changes of fibrosis markers. Parathyroid cell proliferation was markedly increased but without signs of glandular hypertrophy. Skeletal histology showed increased trabecular bone and bone marrow adiposity whereas bone biomarkers (CTX and PINP) suggested higher bone formation, but surprisingly, lower bone resorption and perturbations in mineral metabolism.

Conclusions

We present a novel, non-surgical method for induction of renal failure in mice. This is an important complement to existing uremic models for pathophysiological studies in acute and chronic kidney disease, especially in terms of tubulointerstitial lesions.
Institutional incentives for altruism: gifting blood in China
Authors: Yu Chengpu , Holroyd Eleanor , Cheng Yu , Fai Lau Joseph Tak
Published: May 2013

Background

In mainland China, the motivation behind voluntary blood donation is a relatively new and understudied behavior. In recent times provincial governments in China have implemented various institutional incentive measures. However, little is known regarding the effectiveness of such measures. This qualitative study investigated the nature and outcomes of some identified institutionalized mechanisms, in particular how these were created and distributed in the form of incentives for voluntary blood donation.

Methods

Participatory observations were conducted at two blood donation stations and four blood collecting vehicles in Changsha city, China. In-depth interviews were conducted with 17 staff and 58 blood donors at the aforementioned venues from May to October 2008 in Changsha.

Results

Thematic analysis revealed the operation of four primary type incentives: policy-driven, symbolic, information feedback and role models, which constituted the system of institutional incentives. The current blood reimbursement system was not the primary motivation for blood donation; instead this system was a subtheme of future assurance for emergency blood needs. It was evident that symbolic incentives stressed the meaning and value of blood donation. Furthermore, post-donation information services and the inherent mechanisms of communication, enhanced by some public role models, served to draw the public to donate blood.

Conclusions

At the institutional level, blood donation was not only informed by altruism, but also carried a system of benefit and reward for the donors and their family members. We would recommend that such arrangements, if accommodated effectively into China’s health promotion strategies, would increase the likelihood of blood donation.
What do patients think about HIV mass screening in France? A qualitative study
Authors: Fernandez-Gerlinger Marie Paule , Bernard Erik , Saint-Lary Olivier
Published: May 2013

Background

Since 2009, HIV mass screening of the 15–70-year-old general population in low-risk situations has been recommended in France. This, not yet implemented, untargeted screening would be cost-effective with a positive impact on public health. No previous studies had interrogated primary care patients about it. This study aimed at exploring perceptions of patients attending general practitioner’s on HIV mass screening and at identifying barriers to its implementation.

Methods

We conducted a qualitative study through semi-structured individual interviews. Participants were recruited according to age, gender and location of their physician’s practice. Data analysis was based on triangulation by two researchers.

Results

Twenty-four interviews were necessary to obtain data saturation. HIV transmission was mostly associated with sexual intercourse; main barriers stemming from the screening were related to sexuality, often seen as questioning spouse’s faithfulness. It could interfere with religiosity, implying an upsetting perception of sexuality among the elderly. Patients’ beliefs and perceptions regarding HIV/AIDS, the fear to be screened and difficulties to talk about sexuality were other barriers.

Conclusion

To our knowledge, no studies had previously interrogated primary care patients about barriers to HIV mass screening in France. Although relevance of this untargeted screening is debated in France, our results could be helpful to a better understanding of patients’ attitudes toward this and to an outstanding contribution to reduce the number of new cases of HIV contamination.
Antioxidant mediated protective effect of Parthenium hysterophorus against oxidative damage using in vitro models
Authors: Kumar Shashank , Mishra Amita , Pandey Abhay K
Published: May 2013

Background

Parthenium hysterophorus L. (Asteraceae) is a common weed occurring throughout the globe. In traditional medicine its decoction has been used for treatment of many infectious and degenerative diseases. This work was therefore designed to assess the phytochemical constitution of P. hysterophorus flower and root extracts and to evaluate their reducing power, radical scavenging activity as well as protective efficacy against membrane lipid damage.

Methods

Dried flower and root samples were sequentially extracted with non-polar and polar solvents using Soxhlet apparatus. The phytochemical screening was done using standard chemical methods and thin layer chromatography. Total phenolic content was determined spectrophotometrically. Reducing power and hydroxyl radical scavenging activity assays were used to measure antioxidant activity. Protection against membrane damage was evaluated by inhibition of lipid peroxidation (TBARS assay) in rat kidney homogenate.

Results

Flavonoids, terpenoids, alkaloids and cardiac glycosides were present in all the extract. The total phenol contents in flower and root extracts were found to be in the range 86.69-320.17 mg propyl gallate equivalent (PGE)/g and 55.47-253.84 mg PGE/g, respectively. Comparatively better reducing power was observed in hexane fractions of flower (0.405) and root (0.282). Benzene extract of flower and ethyl acetate fraction of root accounted for appreciable hydroxyl radical scavenging activity (75-77%). Maximum protection against membrane lipid peroxidative damage among flower and root extracts was provided by ethanol (55.26%) and ethyl acetate (48.95%) fractions, respectively. Total phenolic content showed positive correlations with reducing power and lipid peroxidation inhibition (LPOI) % in floral extracts as well as with hydroxyl radical scavenging activity and LPOI % in root extracts.

Conclusion

Study established that phytochemicals present in P. hysterophorus extracts have considerable antioxidant potential as well as lipo-protective activity against membrane damage.
Comparative analysis of the genome sequences and replication profiles of chikungunya virus isolates within the East, Central and South African (ECSA) lineage
Authors: Chen Karen Caiyun , Kam Yiu-Wing , Lin Raymond Pin Tzer , Ng Mary Mah-Lee , Ng Lisa FP , Chu Justin Hann Jang
Published: May 2013

Background

A comparative analysis of the genomic and replication profiles of different geographical chikungunya virus (CHIKV) isolates of the East, Central and South African (ECSA) lineage was performed.

Findings

Analysis of the data revealed the different growth kinetics for the different isolates. Deep genome sequencing analysis further revealed specific amino acid mutations in the viral nsP1, nsP3, nsP4, E1 and E2 proteins in the different isolates. Despite the difference in viral genomic profiles, the virus-induced ultrastructural changes within infected cells remained highly conserved among the different chikungunya virus isolates.

Conclusions

These findings provide insights into the genomic and replication profiles of the re-emerging chikungunya virus isolates of the ECSA lineage.
Community resource centres to improve the health of women and children in Mumbai slums: study protocol for a cluster randomized controlled trial
Authors: Shah More Neena , Das Sushmita , Bapat Ujwala , Rajguru Mahesh , Alcock Glyn , Joshi Wasundhara , Pantvaidya Shanti , Osrin David
Published: May 2013

Background

The trial addresses the general question of whether community resource centers run by a non-government organization improve the health of women and children in slums. The resource centers will be run by the Society for Nutrition, Education and Health Action, and the trial will evaluate their effects on a series of public health indicators. Each resource center will be located in a vulnerable Mumbai slum area and will serve as a base for salaried community workers, supervised by officers and coordinators, to organize the collection and dissemination of health information, provision of services, home visits to identify and counsel families at risk, referral of individuals and families to appropriate services and support for their access, meetings of community members and providers, and events and campaigns on health issues.

Methods/design

A cluster randomized controlled trial in which 20 urban slum areas with resource centers are compared with 20 control areas. Each cluster will contain approximately 600 households and randomized allocation will be in three blocked phases, of 12, 12 and 16 clusters. Any resident of an intervention cluster will be able to participate in the intervention, but the resource centers will target women and children, particularly women of reproductive age and children under 5.

The outcomes will be assessed through a household census after 2 years of resource center operations. The primary outcomes are unmet need for family planning in women aged 15 to 49 years, proportion of children under 5 years of age not fully immunized for their ages, and proportion of children under 5 years of age with weight for height less than 2 standard deviations below the median for age and sex. Secondary outcomes describe adolescent pregnancies, home deliveries, receipt of conditional cash transfers for institutional delivery, other childhood anthropometric indices, use of public sector health and nutrition services, indices of infant and young child feeding, and consultation for violence against women and children.

Trial registration

ISRCTN Register: ISRCTN56183183

Clinical Trials Registry of India: CTRI/2012/09/003004
Peril in the market-classification and dosage of species used as anti-diabetics in Lima, Peru
Authors: Bussmann Rainer W , Paniagua-Zambrana Narel , Chamorro Marinoli Rivas , Moreira Natalia Molina , del Rosario Cuadros Negri María Luisa , Olivera Jose
Published: May 2013

Background

Peru is what Peruvian anthropologist Lupe Camino calls the “health axis” of the old Central Andean culture area stretching from Ecuador to Bolivia. In particular in the North of the country the traditional use of medicinal dates back as far as the first millennium B.C. Both healers, and the wider population, often buy their medicinal plants in local markets, but there is very little comparative information available about which plants are sold under which vernacular name at any given time, for which indication, and which dosage information and information about side effects is given by vendors. For this study we used two traditionally used species groups “Hercampuri” Gentianella spec. (Gentianaceae) and “Pasuchaca” Geranium spec. (Geraniaceae.), found in the Mercado Aviación in Lima, as small, clearly circumscribed plant group frequently used to treat symptoms of diabetes as a test case to study the taxonomy, indications, dosage, indicated side effects, and additional species used as admixtures and hypothesized that: 1. A wide variety of different species is sold under the same common name, and often several common names exist for one species. 2. There is no consistency in the dosage, or a relationship between dosage and species marketed under one name. 3. However, there is consistency in the knowledge about usage and side effects.

Methods

Surveys focusing on medicinal plants sold and their properties were conducted at the Mercado Aviación in Lima in December 2012. Vouchers of all specimens were deposited at the National Herbarium of Peru.

Results and conclusions

Our surveys in Mercado Aviación in Lima yielded four species of Gentianella, two of Geranium, and three additional species from three genera used as common additives that were sold as anti-diabetic. These results indicate that even in case of only a few plant species, used for a very clearly circumscribed application, patients run a considerable risk when purchasing their remedies in the market. The possible side effects in this case are the more serious because diabetes has to be treated long term, and as such the patients are ingesting possible toxic remedies over a long period of time. Much more control, and a much more stringent identification of the material sold in public markets, and entering the global supply chain via internet sales, would be needed.
Defining a novel k-nearest neighbours approach to assess the applicability domain of a QSAR model for reliable predictions
Authors: Sahigara Faizan , Ballabio Davide , Todeschini Roberto , Consonni Viviana
Published: May 2013

Background

With the growing popularity of using QSAR predictions towards regulatory purposes, such predictive models are now required to be strictly validated, an essential feature of which is to have the model’s Applicability Domain (AD) defined clearly. Although in recent years several different approaches have been proposed to address this goal, no optimal approach to define the model’s AD has yet been recognized.

Results

This study proposes a novel descriptor-based AD method which accounts for the data distribution and exploits k-Nearest Neighbours (kNN) principle to derive a heuristic decision rule. The proposed method is a three-stage procedure to address several key aspects relevant in judging the reliability of QSAR predictions. Inspired from the adaptive kernel method for probability density function estimation, the first stage of the approach defines a pattern of thresholds corresponding to the various training samples and these thresholds are later used to derive the decision rule. Criterion deciding if a given test sample will be retained within the AD is defined in the second stage of the approach. Finally, the last stage tries reflecting upon the reliability in derived results taking model statistics and prediction error into account.

Conclusions

The proposed approach addressed a novel strategy that integrated the kNN principle to define the AD of QSAR models. Relevant features that characterize the proposed AD approach include: a) adaptability to local density of samples, useful when the underlying multivariate distribution is asymmetric, with wide regions of low data density; b) unlike several kernel density estimators (KDE), effectiveness also in high-dimensional spaces; c) low sensitivity to the smoothing parameter k; and d) versatility to implement various distances measures. The results derived on a case study provided a clear understanding of how the approach works and defines the model’s AD for reliable predictions.
Effect of immobilized cells in calcium alginate beads in alcoholic fermentation
Authors: Duarte Juliana C , Rodrigues J Augusto R , Moran Paulo J S , Valença Gustavo P , Nunhez José R
Published: May 2013

Saccharomyces cerevisiae cells were immobilized in calcium alginate and chitosan-covered calcium alginate beads and studied in the fermentation of glucose and sucrose for ethanol production. The batch fermentations were carried out in an orbital shaker and assessed by monitoring the concentration of substrate and product with HPLC. Cell immobilization in calcium alginate beads and chitosan-covered calcium alginate beads allowed reuse of the beads in eight sequential fermentation cycles of 10 h each. The final concentration of ethanol using free cells was 40 g L-1 and the yields using glucose and sucrose as carbon sources were 78% and 74.3%, respectively. For immobilized cells in calcium alginate beads, the final ethanol concentration from glucose was 32.9 ± 1.7 g L-1 with a 64.5 ± 3.4% yield, while the final ethanol concentration from sucrose was 33.5 ± 4.6 g L-1 with a 64.5 ± 8.6% yield. For immobilized cells in chitosan-covered calcium alginate beads, the ethanol concentration from glucose was 30.7 ± 1.4 g L-1 with a 61.1 ± 2.8% yield, while the final ethanol concentration from sucrose was 31.8 ± 6.9 g L-1 with a 62.1 ± 12.8% yield. The immobilized cells allowed eight 10 h sequential reuse cycles to be carried out with stable final ethanol concentrations. In addition, there was no need to use antibiotics and no contamination was observed. After the eighth cycle, there was a significant rupture of the beads making them inappropriate for reuse.
Nociceptin Induces Rec8 Phosphorylation and Meiosis in Postnatal Murine Testes
Authors: Eto Ko , Shiotsuki Masahiro , Abe Shin-ichi
Published: May 2013

Phosphorylated Rec8, a key component of cohesin, mediates the association and disassociation, “dynamics,” of chromosomes occurring in synaptonemal complex formation, crossover recombination, and sister chromatid cohesion during meiosis. Yet, the extrinsic factors triggering meiotic chromosome dynamics remain elusive. We have recently found that nociceptin, known as a neuropeptide, is up-regulated by follicle-stimulating hormone in Sertoli cells in postnatal murine testes; however, very little is known about the functional role of nociceptin in spermatogenesis. Here, we show that nociceptin induces Rec8 phosphorylation, triggering chromosome dynamics, in spermatocytes during meiosis in postnatal murine testes. The nociceptin receptor Oprl-1 is exclusively expressed in the plasma membrane of testicular germ cells, mostly spermatocytes. Treatment of testes with nociceptin resulted in a rapid phosphorylation of Rec8. Injection of nociceptin into mice stimulated Rec8 phosphorylation and meiotic chromosome dynamics in testes, whereas injection of nocistatin, a specific inhibitor of nociceptin, abolished them. These findings suggest that nociceptin is a novel extrinsic factor that plays a crucial role in the progress of meiosis.
Cyclooxygenase-2 Regulated by the Nuclear Factor-κB Pathway Plays an Important Role in Endometrial Breakdown in a Female Mouse Menstrual-like Model
Authors: Xu Xiangbo , Chen Xihua , Li Yunfeng , Cao Huizi , Shi Cuige , Guan Shuo , Zhang Shucheng , He Bin , Wang Jiedong
Published: May 2013

The role of prostaglandins (PGs) in menstruation has long been proposed. Although evidence from studies on human and nonhuman primates supports the involvement of PGs in menstruation, whether PGs play an obligatory role in the process remains unclear. Although cyclooxygenase (COX) inhibitors have been used in the treatment of irregular uterine bleeding, the mechanism involved has not been elucidated. In this study, we used a recently established mouse menstrual-like model for investigating the role of COX in endometrial breakdown and its regulation. Administration of the nonspecific COX inhibitor indomethacin and the COX-2 selective inhibitor DuP-697 led to inhibition of the menstrual-like process. Furthermore, immunostaining analysis showed that the nuclear factor (NF)κB proteins P50, P65, and COX-2 colocalized in the outer decidual stroma at 12 to 16 hours after progesterone withdrawal. Chromatin immunoprecipitation analysis showed that NFκB binding to the Cox-2 promoter increased at 12 hours after progesterone withdrawal in vivo, and real-time PCR analysis showed that the NFκB inhibitors pyrrolidine dithiocarbamate and MG-132 inhibited Cox-2 mRNA expression in vivo and in vitro, respectively. Furthermore, COX-2 and NFκB inhibitors similarly reduced endometrial breakdown, suggesting that NFκB/COX-2-derived PGs play a critical role in this process. In addition, the CD45+ leukocyte numbers were sharply reduced following indomethacin (COX-1 and COX-2 inhibitor), DuP-697 (COX-2 inhibitor), and pyrrolidine dithiocarbamate (NFκB inhibitor) treatment. Collectively, these data indicate that NFκB/COX-2-induced PGs regulate leukocyte influx, leading to endometrial breakdown.
MicroRNAs in the Aging Female Brain: A Putative Mechanism for Age-Specific Estrogen Effects
Authors: Rao Yathindar S. , Mott Natasha N. , Wang Yanru , Chung Wilson C.J. , Pak Toni R.
Published: May 2013

Menopause is characterized by the rapid age-related decline of circulating 17β-estradiol (E2) levels in women, which can sometimes result in cognitive disorders such as impaired memory and increased anxiety. Hormone therapy (HT) is a widely used treatment for the adverse effects associated with menopause; however, evidence suggests that HT administered to postmenopausal women age 65 years and over can lead to increased risks for cognitive disorders. We hypothesized that these age-related changes in E2 action are due to posttranscriptional gene regulation by microRNAs (miRNAs). miRNAs are a class of small noncoding RNAs that regulate gene expression by binding to the 3′-untranslated region of target mRNAs and subsequently target these transcripts for degradation. In the present study, 3- and 18-month-old female rats were oophorectomized (OVX) and treated 1 week after surgery with 2.5 μg E2 once per day for 3 days. Total RNA was isolated from the ventral and dorsal hippocampus, central amygdala, and paraventricular nucleus. Our results showed that E2 differentially altered miRNA levels in an age- and brain region-dependent manner. Multiple miRNA target prediction algorithms revealed putative target genes that are important for memory and stress regulation, such as BDNF, glucocorticoid receptor, and SIRT-1. Indeed, quantitative RT-PCR analyses of some of the predicted targets, such as SIRT1, showed that the mRNA expression levels were the inverse of the targeting miRNA, thereby confirming the prediction algorithms. Taken together, these data show that E2 regulates miRNA expression in an age- and E2-dependent manner, which we hypothesize results in differential gene expression and consequently altered neuronal function.
The Drosophila GOLPH3 homolog regulates the biosynthesis of heparan sulfate proteoglycans by modulating the retrograde trafficking of exostosins
Authors: Chang Wei-Ling , Chang Che-Wei , Chang Yu-Yun , Sung Hsin-Ho , Lin Ming-Der , Chang Shu-Chuan , Chen Chung-Hao , Huang Chia-Wei , Tung Kuei-Shu , Chou Tze-Bin
Published: May 2013

The exostosin (EXT) genes encode glycosyltransferases required for glycosaminoglycan chain polymerization in the biosynthesis of heparan sulfate proteoglycans (HSPGs). Mutations in the tumor suppressor genes EXT1 and EXT2 disturb HSPG biosynthesis and cause multiple osteochondroma (MO). How EXT1 and EXT2 traffic within the Golgi complex is not clear. Here, we show that Rotini (Rti), the Drosophila GOLPH3, regulates the retrograde trafficking of EXTs. A reduction in Rti shifts the steady-state distribution of EXTs to the trans-Golgi. These accumulated EXTs tend to be degraded and their re-entrance towards the route for polymerizing GAG chains is disengaged. Conversely, EXTs are mislocalized towards the transitional endoplasmic reticulum/cis-Golgi when Rti is overexpressed. Both loss of function and overexpression of rti result in incomplete HSPGs and perturb Hedgehog signaling. Consistent with Drosophila, GOLPH3 modulates the dynamic retention and protein stability of EXT1/2 in mammalian species. Our data demonstrate that GOLPH3 modulates the activities of EXTs, thus implicating a putative role for GOLPH3 in the formation of MO.
Deficient FGF signaling causes optic nerve dysgenesis and ocular coloboma
Authors: Cai Zhigang , Tao Chenqi , Li Hongge , Ladher Raj , Gotoh Noriko , Feng Gen-Sheng , Wang Fen , Zhang Xin
Published: May 2013

FGF signaling plays a pivotal role in eye development. Previous studies using in vitro chick models and systemic zebrafish mutants have suggested that FGF signaling is required for the patterning and specification of the optic vesicle, but due to a lack of genetic models, its role in mammalian retinal development remains elusive. In this study, we show that specific deletion of Fgfr1 and Fgfr2 in the optic vesicle disrupts ERK signaling, which results in optic disc and nerve dysgenesis and, ultimately, ocular coloboma. Defective FGF signaling does not abrogate Shh or BMP signaling, nor does it affect axial patterning of the optic vesicle. Instead, FGF signaling regulates Mitf and Pax2 in coordinating the closure of the optic fissure and optic disc specification, which is necessary for the outgrowth of the optic nerve. Genetic evidence further supports that the formation of an Frs2α-Shp2 complex and its recruitment to FGF receptors are crucial for downstream ERK signaling in this process, whereas constitutively active Ras signaling can rescue ocular coloboma in the FGF signaling mutants. Our results thus reveal a previously unappreciated role of FGF-Frs2α-Shp2-Ras-ERK signaling axis in preventing ocular coloboma. These findings suggest that components of FGF signaling pathway may be novel targets in the diagnosis of and the therapeutic interventions for congenital ocular anomalies.
Imaging neurite development of adult-born granule cells
Authors: Kleine Borgmann Felix B. , Bracko Oliver , Jessberger Sebastian
Published: May 2013

Neural stem/progenitor cells (NSPCs) generate new neurons throughout life in the mammalian hippocampus. Newborn granule cells mature over several weeks to functionally integrate into the pre-existing neural circuitry. Even though an increasing number of genes that regulate neuronal polarization and neurite extension have been identified, the cellular mechanisms underlying the extension of neurites arising from newborn granule cells remain largely unknown. This is mainly because of the current lack of longitudinal observations of neurite growth within the endogenous niche. Here we used a novel slice culture system of the adult mouse hippocampal formation combined with in vivo retroviral labeling of newborn neurons and longitudinal confocal imaging to analyze the mode and velocity of neurite growth extending from immature granule cells. Using this approach we show that dendritic processes show a linear growth pattern with a speed of 2.19±0.2 μm per hour, revealing a much faster growth dynamic than expected by snapshot-based in vivo time series. Thus, we here identified the growth pattern of neurites extending from newborn neurons within their niche and describe a novel technology that will be useful to monitor neuritic growth in physiological and disease states that are associated with altered dendritic morphology, such as rodent models of epilepsy.
Mucosal candidiasis elicits NF-κB activation, proinflammatory gene expression and localized neutrophilia in zebrafish
Authors: Gratacap Remi L. , Rawls John F. , Wheeler Robert T.
Published: May 2013

The epithelium performs a balancing act at the interface between an animal and its environment to enable both pathogen killing and tolerance of commensal microorganisms. Candida albicans is a clinically important human commensal that colonizes all human mucosal surfaces, yet is largely prevented from causing mucosal infections in immunocompetent individuals. Despite the importance of understanding host-pathogen interactions at the epithelium, no immunocompetent vertebrate model has been used to visualize these dynamics non-invasively. Here we demonstrate important similarities between swimbladder candidiasis in the transparent zebrafish and mucosal infection at the mammalian epithelium. Specifically, in the zebrafish swimbladder infection model, we show dimorphic fungal growth, both localized and tissue-wide epithelial NF-κB activation, induction of NF-κB -dependent proinflammatory genes, and strong neutrophilia. Consistent with density-dependence models of host response based primarily on tissue culture experiments, we show that only high-level infection provokes widespread activation of NF-κB in epithelial cells and induction of proinflammatory genes. Similar to what has been found using in vitro mammalian models, we find that epithelial NF-κB activation can occur at a distance from the immediate site of contact with epithelial cells. Taking advantage of the ability to non-invasively image infection and host signaling at high resolution, we also report that epithelial NF-κB activation is diminished when phagocytes control the infection. This is the first system to model host response to mucosal infection in the juvenile zebrafish, and offers unique opportunities to investigate the tripartite interactions of C. albicans, epithelium and immune cells in an intact host.
Syntheses, Crystal Structure, and Spectroscopic Properties of Meso–Meso-Linked Porphyrin–Corrole Hybrids
Authors: Chen Chen , Zhu Yi-Zhou , Fan Qiao-Jun , Song Hai-Bin , Zheng Jian-Yu
Published: May 2013

Meso–meso directly linked porphyrin (Por)–corrole (Cor) hybrids have been successfully achieved for the first time. The meso–meso linkage has been confirmed by X-ray diffraction analysis. The characteristic split Soret absorption band revealed the existence of strong exciton coupling between porphyrin and corrole subunits. Time-resolved and steady-state fluorescence has also been investigated.
Short duration of antibiotic prophylaxis in open fractures does not enhance risk of subsequent infection
Authors: Dunkel N. , Pittet D. , Tovmirzaeva L. , Suvà D. , Bernard L. , Lew D. , Hoffmeyer P. , Uçkay I.
Published: May 2013

We undertook a retrospective case-control study to assess the clinical variables associated with infections in open fractures. A total of 1492 open fractures were retrieved; these were Gustilo and Anderson grade I in 663 (44.4%), grade II in 370 (24.8%), grade III in 310 (20.8%) and unclassifiable in 149 (10.0%). The median duration of prophylaxis was three days (interquartile range (IQR) 1 to 3), and the median number of surgical interventions was two (1 to 9). We identified 54 infections (3.6%) occurring at a median of ten days (IQR 5 to 20) after trauma. Pathogens intrinsically resistant to the empirical antibiotic regimen used (enterococci, Enterobacter spp, Pseudomonas spp) were documented in 35 of 49 cases (71%). In multivariable regression analyses, grade III fractures and vascular injury or compartment syndrome were significantly associated with infection. Overall, compared with one day of antibiotic treatment, two to three days (odds ratio (OR) 0.6 (95% confidence interval (CI) 0.2 to 2.0)), four to five days (OR 1.2 (95% CI 0.3 to 4.9)), or > five days (OR 1.4 (95% CI 0.4 to 4.4)) did not show any significant differences in the infection risk. These results were similar when multivariable analysis was performed for grade III fractures only (OR 0.3 (95% CI 0.1 to 3.4); OR 0.6 (95% CI 0.2 to 2.1); and OR 1.7 (95% CI 0.5 to 6.2), respectively).

Infection in open fractures is related to the extent of tissue damage but not to the duration of prophylactic antibiotic therapy. Even for grade III fractures, a one-day course of prophylactic antibiotics might be as effective as prolonged prophylaxis.

Cite this article: Bone Joint J 2013;95-B:831–7.
Incidence of graft rupture 15 years after bilateral anterior cruciate ligament reconstructions
Authors: Goddard M. , Salmon L. , Waller A. , Papapetros E. , Pinczewski L. A.
Published: May 2013

Between 1993 and 1994, 891 patients underwent primary anterior cruciate ligament (ACL) reconstruction. A total of 48 patients had undergone bilateral ACL reconstruction and 42 were available for review. These patients were matched to a unilateral ACL reconstruction control group for gender, age, sport of primary injury, meniscal status and graft type. At 15-year follow-up a telephone interview with patients in both groups was performed. The incidence of further ACL injury was identified through structured questions and the two groups were compared for the variables of graft rupture or further ACL injury, family history of ACL injury, International Knee Documentation Committee (IKDC) subjective score and activity level.

There were 28 male and 14 female patients with a mean age of 25 years (13 to 42) at the time of first ACL injury. Subsequent further ACL injury was identified in ten patients (24%) in the bilateral ACL reconstruction study group and in nine patients (21%) in the unilateral ACL reconstruction control group (p = 0.794). The mean time from bilateral ACL reconstruction to further ACL injury was 54 months (6 to 103). There was no significant difference between the bilateral ACL reconstruction study group and the matched unilateral ACL reconstruction control group in incidence of further ACL injury (p = 0.794), family history of ACL injury (p = 0.595), IKDC activity level (p = 0.514), or IKDC subjective score (p = 0.824).

After bilateral ACL reconstruction the incidence of graft rupture and subjective outcomes were equivalent to that after unilateral ACL reconstructions.

Cite this article: Bone Joint J 2013;95-B:798–802.
A comparison of the rates of union after cancellous iliac crest bone graft and Kirschner-wire fixation in the treatment of stable and unstable scaphoid nonunion
Authors: Park H. Y. , Yoon J. O. , Jeon I. H. , Chung H. W. , Kim J. S.
Published: May 2013

This study was performed to determine whether pure cancellous bone graft and Kirschner (K-) wire fixation were sufficient to achieve bony union and restore alignment in scaphoid nonunion. A total of 65 patients who underwent cancellous bone graft and K-wire fixation were included in this study. The series included 61 men and four women with a mean age of 34 years (15 to 72) and mean delay to surgery of 28.7 months (3 to 240). The patients were divided into an unstable group (A) and stable group (B) depending on the pre-operative radiographs. Unstable nonunion was defined as a lateral intrascaphoid angle > 45°, or a radiolunate angle > 10°. There were 34 cases in group A and 31 cases in group B. Bony union was achieved in 30 patients (88.2%) in group A, and in 26 (83.9%) in group B (p = 0.439). Comparison of the post-operative radiographs between the two groups showed no significant differences in lateral intrascaphoid angle (p = 0.657) and scaphoid length (p = 0.670) and height (p = 0.193). The radiolunate angle was significantly different (p = 0.020) but the mean value in both groups was < 10°. Comparison of the dorsiflexion and palmar flexion of movement of the wrist and the mean Mayo wrist score at the final clinical visit in each group showed no significant difference (p = 0.190, p = 0.587 and p = 0.265, respectively). Cancellous bone graft and K-wire fixation were effective in the treatment of stable and unstable scaphoid nonunion.

Cite this article: Bone Joint J 2013;95-B:809–14.