bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of acute diarrhea in adults in China: a cross-sectional survey
Authors: Hou Feng-Qin , Wang Yan , LI Jun , Wang Gui-Qiang , Liu Ying
Published: January 2013

Background

The aim of this study was to evaluate the management of acute adult diarrhea in China and assess adherence of clinical practice to national guidelines and 2012 World Gastroenterology Organization guidelines.

Methods

A cross-sectional survey was carried out among physicians in 20 hospitals in two different areas of China (Beijing, 10; Shaanxi province, 10). Summary statistics were calculated for the overall study group and for each region. Between-region differences were assessed with χ2 or t-tests.

Results

Data were collected for 800 patients (≥18 years; mean ± SD age 37.0 ± 16.3 years; 56.4% female). The mean ± SD time between diarrhea onset and visiting a diarrhea clinic was 2.4 ± 1.6 days; this interval was significantly shorter in Beijing than Shaanxi (2.0 ± 1.4 vs 2.8 ± 1.8 days, respectively; p < 0.001). Overall, 31.4% of patients self-medicated before visiting the clinic, most commonly with antibiotics. Routine stool examinations were ordered for 70.6% of patients, vibrio cholera stool culture for 57.5%, but non-vibrio bacteria stool culture for only 11.4%. Only 61.6% of patients received fluid and electrolyte therapy: 28.3% oral rehydration solution (ORS) and 33.4% intravenous fluids (even though only 13.8% needed). Antibiotics were the most common drugs (60.8%) and the most common antibiotics were fluoroquinolones, followed by aminoglycosides. Totally 51.3% of patients received irrational antibiotic treatment (unnecessary for 47.9%; indicated but not prescribed for 3.4%). After antibiotics, the most commonly prescribed drugs were dioctahedral smectite (59.3%); For Shaanxi compared with Beijing, less individuals received ORS (7.8% vs 48.5%,respectively; p < 0.001) and more received intravenous fluids (46.3% vs 20.5%, respectively; p < 0.001). Significantly more of the patients in Shaanxi province were administered antibiotics (64.5% vs 57%, respectively; p = 0.03), and more received intravenous antibiotics than Beijing (49.0% vs 27.0%, respectively; p < 0.001).

Conclusions

Adherence to both national guidelines and 2012 World Gastroenterology Organization guidelines for the management of acute diarrhea in adult was limited among tertiary hospital physicians. The findings suggest nationwide education and effective health policies are needed to improve medical practice and reduce the unnecessary burden on the healthcare system.
Subchondral pre-solidified chitosan/blood implants elicit reproducible early osteochondral wound-repair responses including neutrophil and stromal cell chemotaxis, bone resorption and repair, enhanced repair tissue integration and delayed matrix deposition
Authors: Lafantaisie-Favreau Charles-Hubert , Guzmán-Morales Jessica , Sun Jun , Chen Gaoping , Harris Adam , Smith Thomas D , Carli Alberto , Henderson Janet , Stanish William D , Hoemann Caroline D
Published: January 2013

Background

In this study we evaluated a novel approach to guide the bone marrow-driven articular cartilage repair response in skeletally aged rabbits. We hypothesized that dispersed chitosan particles implanted close to the bone marrow degradein situin a molecular mass-dependent manner, and attract more stromal cells to the site in aged rabbits compared to the blood clot in untreated controls.

Methods

Three microdrill hole defects, 1.4 mm diameter and 2 mm deep, were created in both knee trochlea of 30 month-old New Zealand White rabbits. Each of 3 isotonic chitosan solutions (150, 40, 10 kDa, 80% degree of deaceylation, with fluorescent chitosan tracer) was mixed with autologous rabbit whole blood, clotted with Tissue Factor to form cylindrical implants, and press-fit in drill holes in the left knee while contralateral holes received Tissue Factor or no treatment. At day 1 or day 21 post-operative, defects were analyzed by micro-computed tomography, histomorphometry and stereology for bone and soft tissue repair.

Results

All 3 implants filled the top of defects at day 1 and were partly degradedin situat 21 days post-operative. All implants attracted neutrophils, osteoclasts and abundant bone marrow-derived stromal cells, stimulated bone resorption followed by new woven bone repair (bone remodeling) and promoted repair tissue-bone integration. 150 kDa chitosan implant was less degraded, and elicited more apoptotic neutrophils and bone resorption than 10 kDa chitosan implant. Drilled controls elicited a poorly integrated fibrous or fibrocartilaginous tissue.

Conclusions

Pre-solidified implants elicit stromal cells and vigorous bone plate remodeling through a phase involving neutrophil chemotaxis. Pre-solidified chitosan implants are tunable by molecular mass, and could be beneficial for augmented marrow stimulation therapy if the recruited stromal cells can progress to bone and cartilage repair.
Service quality, trust, and patient satisfaction in interpersonal-based medical service encounters
Authors: Chang Ching-Sheng , Chen Su-Yueh , Lan Yi-Ting
Published: January 2013

Background

Interaction between service provider and customer is the primary core of service businesses of different natures, and the influence of trust on service quality and customer satisfaction could not be ignored in interpersonal-based service encounters. However, lack of existing literature on the correlation between service quality, patient trust, and satisfaction from the prospect of interpersonal-based medical service encounters has created a research gap in previous studies. Therefore, this study attempts to bridge such a gap with an evidence-based practice study.

Methods

We adopted a cross-sectional design using a questionnaire survey of outpatients in seven medical centers of Taiwan. Three hundred and fifty copies of questionnaire were distributed, and 285 valid copies were retrieved, with a valid response rate of 81.43%. The SPSS 14.0 and AMOS 14.0 (structural equation modeling) statistical software packages were used for analysis. Structural equation modeling clarifies the extent of relationships between variables as well as the chain of cause and effect. Restated, SEM results do not merely show empirical relationships between variables when defining the practical situation. For this reason, SEM was used to test the hypotheses.

Results

Perception of interpersonal-based medical service encounters positively influences service quality and patient satisfaction. Perception of service quality among patients positively influences their trust. Perception of trust among patients positively influences their satisfaction.

Conclusions

According to the findings, as interpersonal-based medical service encounters will positively influence service quality and patient satisfaction, and the differences for patients’ perceptions of the professional skill and communication attitude of personnel in interpersonal-based medical service encounters will influence patients’ overall satisfaction in two ways: (A) interpersonal-based medical service encounter directly affects patient satisfaction, which represents a direct effect; and (B) service quality and patient trust are used as intervening variables to affect patient satisfaction, which represents an indirect effect. Due to differences in the scale, resources and costs among medical institutions of different levels, it is a most urgent and concerning issue of how to control customers’ demands and preferences and adopt correct marketing concepts under the circumstances of intense competition in order to satisfy the public and build up a competitive edge for medical institutions.
The prevalence and ingredient cost of chronic comorbidity in the Irish elderly population with medication treated type 2 diabetes: A retrospective cross-sectional study using a national pharmacy claims database
Authors: O’Shea Miriam , Teeling Mary , Bennett Kathleen
Published: January 2013

Background

Comorbidity in patients with diabetes is associated with poorer health and increased cost. The aim of this study was to investigate the prevalence and ingredient cost of comorbidity in patients ≥ 65 years with and without medication treated type 2 diabetes using a national pharmacy claims database.

Methods

The Irish Health Service Executive Primary Care Reimbursement Service pharmacy claims database, which includes all prescribing to individuals covered by the General Medical Services scheme, was used to identify the study population (≥ 65 years). Patients with medication treated type 2 diabetes (T2DM) were identified using the prescription of oral anti-hyperglycaemic agents alone or in combination with insulin as a proxy for disease diagnosis. The prevalence and ingredient prescribing cost of treated chronic comorbidity in the study population with and without medication treated T2DM were ascertained using a modified version of the RxRiskV index, a prescription based comorbidity index. The association between T2DM and comorbid conditions was assessed using logistic regression adjusting for age and sex. Bootstrapping was used to ascertain the mean annual ingredient cost of treated comorbidity. Statistical significance at p < 0.05 was assumed.

Results

In 2010, 43165 of 445180 GMS eligible individuals (9.7%) were identified as having received medication for T2DM. The median number of comorbid conditions was significantly higher in those with T2DM compared to without (median 5 vs. 3 respectively; p < 0.001). Individuals with T2DM were more likely to have ≥ 5 comorbidities when compared to those without (OR = 2.82, 95% CI = 2.76-2.88, p < 0.0001). The mean annual ingredient cost for comorbidity was higher in the study population with T2DM (€1238.67, 95% CI = €1238.20 - €1239.14) compared to those without the condition (€799.28, 95% CI = €799.14 - € 799.41).

Conclusions

Individuals with T2DM were more likely to have a higher number of treated comorbid conditions than those without and this was associated with higher ingredient costs. This has important policy and economic consequences for the planning and provision of future health services in Ireland, given the expected increase in T2DM and other chronic conditions.
Numerical investigation of stagnation point flow over a stretching sheet with convective boundary conditions
Authors: Mohamed Muhammad Khairul Anuar , Salleh Mohd Zuki , Nazar Roslinda , Ishak Anuar
Published: January 2013

In this study, the mathematical modeling for stagnation point flow over a stretching surface with convective boundary conditions is considered. The transformed boundary layer equations are solved numerically using the shooting method. Numerical solutions are obtained for the skin friction coefficient, the surface temperature as well as the velocity profiles. The features of the flow and heat transfer characteristics for various values of the Prandtl number, stretching parameter and conjugate parameter are analyzed and discussed.
Topographic models for predicting malaria vector breeding habitats: potential tools for vector control managers
Authors: Nmor Jephtha C , Sunahara Toshihiko , Goto Kensuke , Futami Kyoko , Sonye George , Akweywa Peter , Dida Gabriel , Minakawa Noboru
Published: January 2013

Background

Identification of malaria vector breeding sites can enhance control activities. Although associations between malaria vector breeding sites and topography are well recognized, practical models that predict breeding sites from topographic information are lacking. We used topographic variables derived from remotely sensed Digital Elevation Models (DEMs) to model the breeding sites of malaria vectors. We further compared the predictive strength of two different DEMs and evaluated the predictability of various habitat types inhabited by Anopheles larvae.

Methods

Using GIS techniques, topographic variables were extracted from two DEMs: 1) Shuttle Radar Topography Mission 3 (SRTM3, 90-m resolution) and 2) the Advanced Spaceborne Thermal Emission Reflection Radiometer Global DEM (ASTER, 30-m resolution). We used data on breeding sites from an extensive field survey conducted on an island in western Kenya in 2006. Topographic variables were extracted for 826 breeding sites and for 4520 negative points that were randomly assigned. Logistic regression modelling was applied to characterize topographic features of the malaria vector breeding sites and predict their locations. Model accuracy was evaluated using the area under the receiver operating characteristics curve (AUC).

Results

All topographic variables derived from both DEMs were significantly correlated with breeding habitats except for the aspect of SRTM. The magnitude and direction of correlation for each variable were similar in the two DEMs. Multivariate models for SRTM and ASTER showed similar levels of fit indicated by Akaike information criterion (3959.3 and 3972.7, respectively), though the former was slightly better than the latter. The accuracy of prediction indicated by AUC was also similar in SRTM (0.758) and ASTER (0.755) in the training site. In the testing site, both SRTM and ASTER models showed higher AUC in the testing sites than in the training site (0.829 and 0.799, respectively). The predictability of habitat types varied. Drains, foot-prints, puddles and swamp habitat types were most predictable.

Conclusions

Both SRTM and ASTER models had similar predictive potentials, which were sufficiently accurate to predict vector habitats. The free availability of these DEMs suggests that topographic predictive models could be widely used by vector control managers in Africa to complement malaria control strategies.
Seroprevalence and risk factors for Toxoplasmosis in HIV infected and non-infected individuals in Bahir Dar, Northwest Ethiopia
Authors: Walle Fisseha , Kebede Nigatu , Tsegaye Aster , Kassa Tesfu
Published: January 2013

Background

Toxoplasmosis, a zoonotic disease distributed worldwide, is an infection caused by the ubiquitous obligatory intracellular coccidian protozoan organism,Toxoplasma gondii. It is a major public health concern because the disease is serious in terms of mortality or physical and /or psychological sequellae in patients with HIV disease. The aim of the study was to assess the seroprevalence ofToxoplasma gondiiIgG and IgM antibodies and associated risk factors in HIV infected and non-infected individuals attending Felege Hiwot referral hospital, Bahir Dar, Northwest Ethiopia.

Methods

A cross sectional study was conducted at Felege Hiwot referral hospital, Bahir Dar, Amhara National Regional State. Venous blood samples were collected from 103 HIV infected pre anti-retroviral therapy patients at Felege Hiwot referral hospital and 101 HIV negative apparently healthy voluntary blood donors at the blood bank. Serum samples were analyzed for anti-Toxoplasma gondiiIgG and IgM antibodies using a commercially available ELISA kit. Socio-demographic and associated risk factors forToxoplasmosisfrom each individual were also obtained and the data was analyzed using SPSS version 18.

Results

Of the examined HIV seropositive individuals, 87.4% (90/103) and 10.7% (11/103) were positive for anti-T.gondiiIgG and IgM antibodies, respectively. Multivariate analysis using logistic regression showed that anti-T. gondiiseropositivity was independently significantly associated with undercooked or raw meat consumption (adjusted OR=5.73, 95% CI=1.35-24.39; P=0.02) and having contact with cat (adjusted OR= 4.29, 95% CI=1.08-16.94; P=0.04) in HIV positive individuals. In HIV negative apparently healthy blood donors, prevalence of anti-T. gondiiantibodies were 70.29% and 2.97% for IgG and IgM, respectively. Multivariate analysis showed that undercooked or raw meat consumption (adjusted OR=6.45, 95% CI=2.16-19.28; p=0.001) and sex (OR=6.79, 95% CI=2.14-21.60; p=0.001) were independently significantly associated with anti-T. gondiiIgG seropositivity, with a significantly higher number of males affected than females.

Conclusion

The present findings showed a high sero-prevalence of anti-T. gondiiantibodies in HIV infected pre-ART and HIV non-infected apparently healthy blood donors in Bahir Dar. Consumption of undercooked or raw meat might greatly contribute towards acquiringT. gondiiinfection in HIV infected pre-ART and HIV non-infected apparently healthy blood donors. It may be appropriate to include routine serological screening test for determination of anti-T. gondiiantibodies in HIV infected pre-ART individuals and HIV negative apparently healthy blood donors. In addition, health education towards avoiding eating undercooked and raw meat, and avoiding contact with cats were recommended.
Channel-mediated astrocytic glutamate release via Bestrophin-1 targets synaptic NMDARs
Authors: Han Kyung-Seok , Woo Junsung , Park Hyungju , Yoon Bong-June , Choi Sukwoo , Lee C Justin
Published: January 2013

Background

Astrocytes regulate neuronal excitability and synaptic activity by releasing gliotransmitters such as glutamate. Our recent study demonstrated that astrocytes release glutamate upon GPCR activation via Ca2+ activated anion channel, Bestrophin-1 (Best1). The target of Best1-mediated astrocytic glutamate has been shown to be the neuronal NMDA receptors (NMDAR). However, whether it targets synaptically or extra-synaptically localized NMDAR is not known.

Findings

We recorded spontaneous miniature excitatory postsynaptic currents (mEPSCs) from CA1 pyramidal cells to test whether Best1-mediated astrocytic glutamate targets synaptic NMDAR. An agonist of protease activated receptor 1 (PAR1) was used to induce astrocytic Ca2+ increase and glutamate release. Firstly, we found that activation of PAR1 and subsequent release of glutamate from astrocyte does not alone increase the frequency of mEPSCs. Secondly, we found that mEPSC rise time is variable depending on the different electrotonic distances from the somatic recording site to the synaptic region where each mEPSC occurs. Two subgroups of mEPSC from CA1 pyramidal neuron by rise time were selected and analyzed. One group is fast rising mEPSCs with a rise time of 1 ~ 5 ms, representing synaptic activities arising from proximal dendrites. The other group is slowly rising mEPSCs with a rise time of 5 ~ 10 ms, representing synaptic events arising from glutamate release at synapses located in the distal dendrites. We used cell-type specific Best1 gene silencing system by Cre-loxP cleavage to dissociate the effect of neuronal and astrocytic Best1. Astrocytic Best1-mediated glutamate release by PAR1 activation did not affect decay kinetics, frequency, and amplitude of fast rising mEPSC. In contrast, PAR1 activation resulted in an NMDA receptor component to be present on slowly rising mEPSC, but did not alter frequency or amplitude.

Conclusions

Our results indicate that astrocytic glutamate via Best1 channel targets and activates synaptic NMDARs.
Heme oxygenase 1 improves glucoses metabolism and kidney histological alterations in diabetic rats
Authors: Ptilovanciv Ellen ON , Fernandes Gabryelle S , Teixeira Luciana C , Reis Luciana A , Pessoa Edson A , Convento Marcia B , Simões Manuel J , Albertoni Guilherme A , Schor Nestor , Borges Fernanda T
Published: January 2013

One important concern in the treatment of diabetes is the maintenance of glycemic levels and the prevention of diabetic nephropathy. Inducible heme oxygenase 1 (HO-1) is a rate-limiting enzyme thought to have antioxidant and cytoprotective roles. The goal of the present study was to analyze the effect of HO-1 induction in chronically hyperglycemic rats. The hyperglycemic rats were divided into two groups: one group, called STZ, was given a single injection of streptozotocin; and the other group was given a single streptozotocin injection as well as daily injections of hemin, an HO-1 inducer, over 60 days (STZ + HEME). A group of normoglycemic, untreated rats was used as the control (CTL).

Body weight, diuresis, serum glucose levels, microalbuminuria, creatinine clearance rate, urea levels, sodium excretion, and lipid peroxidation were analyzed. Histological alterations and immunohistochemistry for HO-1 and inducible nitric oxide synthase (iNOS) were assessed. After 60 days, the STZ group exhibited an increase in blood glucose, diuresis, urea, microalbuminuria, and sodium excretion. There was no weight gain, and there was a decrease in creatinine clearance in comparison to the CTL group. In the STZ + HEME group there was an improvement in the metabolic parameters and kidney function, a decrease in blood glucose, serum urea, and microalbuminuria, and an increase of creatinine clearance, in comparison to the STZ group.

There was glomerulosclerosis, collagen deposition in the STZ rats and increase in iNOS and HO-1 expression. In the STZ + HEME group, the glomerulosclerosis and fibrosis was prevented and there was an increase in the expression of HO-1, but decrease in iNOS expression and lipid peroxidation. In conclusion, our data suggest that chronic induction of HO-1 reduces hyperglycemia, improves glucose metabolism and, at least in part, protects the renal tissue from hyperglycemic injury, possibly through the antioxidant activity of HO-1.
Structural health monitoring of a cantilever beam using support vector machine
Authors: Satpal Satish B , Khandare Yogesh , Guha Anirban , Banerjee Sauvik
Published: January 2013

In this article, the effectiveness of support vector machine (SVM) is examined for health monitoring of beam-like structures using vibration-induced modal displacement data. The SVM is used to predict the intensity or location of damage in a simulated cantilever beam from displacements of the first mode shape. Twelve levels of damage intensities have been simulated at 12 locations, and six levels of white Gaussian noise have been added, thereby obtaining 1,008 simulations. About 90% of these are used for training the SVM, and the remaining are used for testing. The trained SVM is able to predict damage intensity and location of all the training set data with nearly 100% accuracy. The test set data reveal that SVM is able to predict damage intensity and damage location with errors varying from 0.28% to 4.57% and 0% to 20.3%, respectively, when there is no noise in the data. Addition of noise degrades the performance of SVM, the degradation being significant for intensity prediction and less for damage location prediction. The results demonstrate the use of SVM as a powerful tool for structural health monitoring without using the data of healthy state.
Lung cancer screening: from imaging to biomarker
Authors: Xiang Dong , Zhang Bicheng , Doll Donald , Shen Kui , Kloecker Goetz , Freter Carl
Published: January 2013

Despite several decades of intensive effort to improve the imaging techniques for lung cancer diagnosis and treatment, primary lung cancer is still the number one cause of cancer death in the United States and worldwide. The major causes of this high mortality rate are distant metastasis evident at diagnosis and ineffective treatment for locally advanced disease. Indeed, approximately forty percent of newly diagnosed lung cancer patients have distant metastasis. Currently, the only potential curative therapy is surgical resection of early stage lung cancer. Therefore, early detection of lung cancer could potentially increase the chance of cure by surgery and underlines the importance of screening and detection of lung cancer. In the past fifty years, screening of lung cancer by chest X-Ray (CXR), sputum cytology, computed tomography (CT), fluorescence endoscopy and low-dose spiral CT (LDCT) has not improved survival except for the recent report in 2010 by the National Lung Screening Trial (NLST), which showed a 20 percent mortality reduction in high risk participants screened with LDCT compared to those screened with CXRs. Furthermore, serum biomarkers for detection of lung cancer using free circulating DNA and RNA, exosomal microRNA, circulating tumor cells and various lung cancer specific antigens have been studied extensively and novel screening methods are being developed with encouraging results. The history of lung cancer screening trials using CXR, sputum cytology and LDCT, as well as results of trials involving various serum biomarkers, are reviewed herein.
Kinetic modeling: a predictive tool for the adsorption of zinc ions onto calcium alginate beads
Authors: Kafshgari Morteza Hasanzadeh , Mansouri Mohsen , Khorram Mohammad , Kashani Shahab Rahimi
Published: January 2013

Background

The main purpose of this study is to develop a nonlinear model of a batch adsorption and to evaluate the model's capability in the prediction of experimental adsorption data. Additionally, results of the nonlinear model were compared with data of pseudo first- and second-order models. Experimental data were extracted from the adsorption of zinc ions using calcium alginate beads prepared via electrospray method. In order to study the effects of biosorbent porosity and the initial concentration of the zinc solution on adsorption kinetics, calcium alginate beads were prepared with two different porosities and zinc concentrations.

Results

The results revealed that the nonlinear model offers a much more accurate prediction compared with other models as the average root mean square deviation of the nonlinear model was calculated to be only 2.66%, which was smaller at least four times than that of others. Furthermore, the nonlinear model showed that diffusive transport through beads was limited by pore diffusion.

Conclusions

The nonlinear model provided a good fit to the experimental data as the calculated equilibrium adsorptions were shown to be in good agreement with their experimental counterparts.
18F-florbetaben Aβ imaging in mild cognitive impairment
Authors: Ong Kevin , Villemagne Victor L , Bahar-Fuchs Alex , Lamb Fiona , Chételat Gaël , Raniga Parnesh , Mulligan Rachel S , Salvado Olivier , Putz Barbara , Roth Katrin , Masters Colin L , Reininger Cornelia B , Rowe Christopher C
Published: January 2013

Introduction

18F-florbetaben and positron emission tomography were used to examine the relationships between β-amyloid (Aβ) deposition, cognition, hippocampal volume, and white matter hyperintensities in mild cognitive impairment (MCI).

Methods

Forty-five MCI participants were evaluated. A neocortical standardized uptake value ratio threshold ≥ 1.45 was used to discriminate high from low Aβ burden. Correlations were adjusted for age, gender and years of education.

Results

High Aβ burden was found in 53% of MCI. Regression analyses showed standardized uptake value ratio (r = -0.51, P = 0.0015) and hippocampal volume (r = 0.60, P = 0.024) both contributing to episodic memory impairment in independent fashion. White matter hyperintensities correlated with nonmemory cognition, and this correlation was particularly associated with Aβ burden.

Conclusion

Higher Aβ deposition in MCI is associated with more severe memory impairment and is contributing to early amnestic symptoms independent of hippocampal atrophy.
The Metabolite GnRH-(1-5) Inhibits the Migration of Immortalized GnRH Neurons
Authors: Larco Darwin O. , Cho-Clark Madelaine , Mani Shaila K. , Wu T. John
Published: January 2013

The decapeptide GnRH is an important regulator of reproductive behavior and function. In the extracellular matrix, GnRH is metabolized by the endopeptidase EC3.4.24.15 (EP24.15) to generate the pentapeptide GnRH-(1-5). In addition to its expression in the adult hypothalamus, EP24.15 is expressed along the migratory path of GnRH-expressing neurons during development. Although we have previously demonstrated a role for EP24.15 in the generation of the biologically active pentapeptide GnRH-(1-5) in regulating GnRH expression and mediating sexual behavior during adulthood in rodents, the modulatory role of GnRH-(1-5) in the migration of GnRH neurons during development remains unknown. To address this information gap, we examined the effect of GnRH-(1-5) on the cellular migration of a premigratory GnRH-secreting neuronal cell line, the GN11 cell, using a wound-healing assay. Dose- and time-response studies demonstrated that GnRH-(1-5) significantly delayed wound closure. We then sought to identify the mechanism by which GnRH-(1-5) inhibits migration. Because the cognate GnRH receptor is a G protein-coupled receptor, we examined whether GnRH-(1-5) regulates migration by also activating a G protein-coupled receptor. Using a high-throughput β-arrestin recruitment assay, we identified an orphan G protein-coupled receptor (GPR173) that was specifically activated by GnRH-(1-5). Interestingly, small interfering RNA to GPR173 reversed the GnRH-(1-5)−mediated inhibition on migration of GN11 neurons. Furthermore, we also demonstrate that the GnRH-(1-5)−activated GPR173-dependent signal transduction pathway involves the activation of the signal transducer and activator of transcription 3 in GnRH migration. These findings indicate a potential regulatory role for GnRH-(1-5) in GnRH neuronal migration during development.
Trans-Golgi network morphology and sorting is regulated by prolyl-oligopeptidase-like protein PREPL and the AP-1 complex subunit μ1A
Authors: Radhakrishnan Karthikeyan , Baltes Jennifer , Creemers John W. M. , Schu Peter
Published: January 2013

The AP-1 complex recycles between membranes and the cytoplasm and dissociates from membranes during clathrin-coated-vesicle uncoating, but also independently of vesicular transport. The μ1A N-terminal 70 amino acids are involved in regulating AP-1 recycling. In a yeast two-hybrid library screen we identified the cytoplasmic prolyl-oligopeptidase-like protein PREPL as an interaction partner of this domain. PREPL overexpression leads to reduced AP-1 membrane binding, whereas reduced PREPL expression increases membrane binding and impairs AP-1 recycling. Altered AP-1 membrane binding in PREPL-deficient cells mirrors the membrane binding of the mutant AP-1* complex, which is not able to bind PREPL. Colocalisation of PREPL with residual membrane-bound AP-1 can be demonstrated. Patient cell lines deficient in PREPL have an expanded trans-Golgi network, which could be rescued by PREPL expression. These data demonstrate PREPL as an AP-1 effector that takes part in the regulation of AP-1 membrane binding. PREPL is highly expressed in brain and at lower levels in muscle and kidney. Its deficiency causes hypotonia and growth hormone hyposecretion, supporting essential PREPL functions in AP-1-dependent secretory pathways.
Chk1 and Mps1 jointly regulate correction of merotelic kinetochore attachments
Authors: Petsalaki Eleni , Zachos George
Published: January 2013

If uncorrected, merotelic kinetochore attachments can induce mis-segregated chromosomes in anaphase. We show that checkpoint kinase 1 (Chk1) protects vertebrate cells against merotelic attachments and lagging chromosomes and is required for correction of merotelic attachments during a prolonged metaphase. Decreased Chk1 activity leads to hyper-stable kinetochore microtubules, unstable binding of MCAK, Kif2b and Mps1 to centromeres or kinetochores and reduced phosphorylation of Hec1 by Aurora-B. Phosphorylation of Aurora-B at serine 331 (Ser331) by Chk1 is high in prometaphase and decreases significantly in metaphase cells. We propose that Ser331 phosphorylation is required for optimal localization of MCAK, Kif2b and Mps1 to centromeres or kinetochores and for Hec1 phosphorylation. Furthermore, inhibition of Mps1 activity diminishes initial recruitment of MCAK and Kif2b to centromeres or kinetochores, impairs Hec1 phosphorylation and exacerbates merotelic attachments in Chk1-deficient cells. We propose that Chk1 and Mps1 jointly regulate Aurora-B, MCAK, Kif2b and Hec1 to correct merotelic attachments. These results suggest a role for Chk1 and Mps1 in error correction.
In Hippocampal Oriens Interneurons Anti-Hebbian Long-Term Potentiation Requires Cholinergic Signaling via α7 Nicotinic Acetylcholine Receptors
Authors: Griguoli Marilena , Cellot Giada , Cherubini Enrico
Published: January 2013

In the hippocampus, at excitatory synapses between principal cell and oriens/alveus (O/A) interneurons, a particular form of NMDA-independent long-term synaptic plasticity (LTP) has been described (Lamsa et al., 2007). This type of LTP occurs when presynaptic activation coincides with postsynaptic hyperpolarization. For this reason it has been named “anti-Hebbian” to distinguish from the classical Hebbian type of associative learning where presynaptic glutamate release coincides with postsynaptic depolarization. The different voltage dependency of LTP induction is thought to be mediated by calcium-permeable (CP) AMPA receptors that, due to polyamine-mediated rectification, favor calcium entry at hyperpolarized potentials. Here, we report that the induction of this form of LTP needs CP-α7 nicotinic acetylcholine receptors (nAChRs) that, like CP-AMPARs, exhibit a strong inward rectification because of polyamine block at depolarizing potentials. We found that high-frequency stimulation of afferent fibers elicits synaptic currents mediated by α7 nAChRs. Hence, LTP was prevented by α7 nAChR antagonists dihydro-β-erythroidine and methyllycaconitine (MLA) and was absent in α7−/−mice. In addition, in agreement with previous observations (Le Duigou and Kullmann, 2011), in a minority of O/A interneurons in MLA-treated hippocampal slices from WT animals and α7−/−mice, a form of LTP probably dependent on the activation of group I metabotropic glutamate receptors was observed. These data indicate that, in O/A interneurons, anti-Hebbian LTP critically depends on cholinergic signaling via α7 nAChR. This may influence network oscillations and information processing.
Gustatory Sensing Mechanism Coding for Multiple Oviposition Stimulants in the Swallowtail Butterfly,Papilio Xuthus
Authors: Ryuda Masasuke , Calas-List Delphine , Yamada Ayumi , Marion-Poll Frédéric , Yoshikawa Hiroshi , Tanimura Teiichi , Ozaki Katsuhisa
Published: January 2013

The swallowtail butterfly,Papilio xuthus, selectively uses a limited number of plants in the Rutaceae family. The butterfly detects oviposition stimulants in leaves through foreleg chemosensilla and requires a specific combination of multiple oviposition stimulants to lay eggs on the leaf of its host plants. In this study, we sought to elucidate the mechanism underlying the regulation of oviposition behavior by multiple oviposition stimulants. We classified chemosensilla on the tarsomere of the foreleg into three types (L1, L2, and S) according to their size and response to oviposition stimulants and general tastants. The L1 was more abundant in females than in males and responded preferentially to oviposition stimulants. Both L2 and S were common to both sexes and responded to general tastants. We found that five oviposition stimulants (synephrine, stachydrine, 5-hydroxy-Nω-methyltryptamine, narirutin, andchiro-inositol) elicited spikes from three specific gustatory receptor neurons (GRNs) within L1 sensilla. These three GRNs responded to a mixture of the five stimulants at concentrations equivalent to those found in the whole-leaf extract of citrus, and the mixture induced oviposition at levels comparable to whole-leaf extract. We propose that oviposition is triggered by the firing of three specific GRNs in L1 sensilla that encode the chemical signatures of multiple oviposition stimulants.
Computational Substrates of Norms and Their Violations during Social Exchange
Authors: Xiang Ting , Lohrenz Terry , Montague P. Read
Published: January 2013

Social norms in humans constrain individual behaviors to establish shared expectations within a social group. Previous work has probed social norm violations and the feelings that such violations engender; however, a computational rendering of the underlying neural and emotional responses has been lacking. We probed norm violations using a two-party, repeated fairness game (ultimatum game) where proposers offer a split of a monetary resource to a responder who either accepts or rejects the offer. Using a norm-training paradigm where subject groups are preadapted to either high or low offers, we demonstrate that unpredictable shifts in expected offers creates a difference in rejection rates exhibited by the two responder groups for otherwise identical offers. We constructed an ideal observer model that identified neural correlates of norm prediction errors in the ventral striatum and anterior insula, regions that also showed strong responses to variance-prediction errors generated by the same model. Subjective feelings about offers correlated with these norm prediction errors, and the two signals displayed overlapping, but not identical, neural correlates in striatum, insula, and medial orbitofrontal cortex. These results provide evidence for the hypothesis that responses in anterior insula can encode information about social norm violations that correlate with changes in overt behavior (changes in rejection rates). Together, these results demonstrate that the brain regions involved in reward prediction and risk prediction are also recruited in signaling social norm violations.
Bone Morphogenetic Protein 4 Mediates Estrogen-Regulated Sensory Axon Plasticity in the Adult Female Reproductive Tract
Authors: Bhattacherjee Aritra , Rumi M. A. Karim , Staecker Hinrich , Smith Peter G.
Published: January 2013

Peripheral axons are structurally plastic even in the adult, and altered axon density is implicated in many disorders and pain syndromes. However, mechanisms responsible for peripheral axon remodeling are poorly understood. Physiological plasticity is characteristic of the female reproductive tract: vaginal sensory innervation density is low under high estrogen conditions, such as term pregnancy, whereas density is high in low-estrogen conditions, such as menopause. We exploited this system in rats to identify factors responsible for adult peripheral neuroplasticity. Calcitonin gene-related peptide-immunoreactive sensory innervation is distributed primarily within the vaginal submucosa. Submucosal smooth muscle cells express bone morphogenetic protein 4 (BMP4). With low estrogen, BMP4 expression was elevated, indicating negative regulation by this hormone. Vaginal smooth muscle cells induced robust neurite outgrowth by cocultured dorsal root ganglion neurons, which was prevented by neutralizing BMP4 with noggin or anti-BMP4. Estrogen also prevented axon outgrowth, and this was reversed by exogenous BMP4. Nuclear accumulation of phosphorylated Smad1, a primary transcription factor for BMP4 signaling, was high in vagina-projecting sensory neurons after ovariectomy and reduced by estrogen. BMP4 regulation of innervation was confirmedin vivousing lentiviral transduction to overexpress BMP4 in an estrogen-independent manner. Submucosal regions with high virally induced BMP4 expression had high innervation density despite elevated estrogen. These findings show that BMP4, an important factor in early nervous system development and regeneration after injury, is a critical mediator of adult physiological plasticity as well. Altered BMP4 expression may therefore contribute to sensory hyperinnervation, a hallmark of several pain disorders, including vulvodynia.
Temperature Integration at the AC Thermosensory Neurons inDrosophila
Authors: Tang Xin , Platt Michael D. , Lagnese Christopher M. , Leslie Jennifer R. , Hamada Fumika N.
Published: January 2013

Temperature sensation has a strong impact on animal behavior and is necessary for animals to avoid exposure to harmful temperatures. It is now well known that thermoTRP (transient receptor potential) channels in thermosensory neurons detect a variable range of temperature stimuli. However, little is known about how a range of temperature information is relayed and integrated in the neural circuits. Here, we show novel temperature integration between two warm inputs viaDrosophilaTRPA channels, TRPA1 and Pyrexia (Pyx). The internal AC (anterior cell) thermosensory neurons, which express TRPA1, detect warm temperatures and mediate temperature preference behavior. We found that the AC neurons were activated twice when subjected to increasing temperatures. The first response was at ∼25°C via TRPA1 channel, which is expressed in the AC neurons. The second response was at ∼27°C via the second antennal segments, indicating that the second antennal segments are involved in the detection of warm temperatures. Further analysis reveals thatpyx-Gal4-expressing neurons have synapses on the AC neurons and that mutation ofpyxeliminates the second response of the AC neurons. These data suggest that AC neurons integrate both their own TRPA1-dependent temperature responses and a Pyx-dependent temperature response from the second antennal segments. Our data reveal the first identification of temperature integration, which combines warm temperature information from peripheral to central neurons and provides the possibility that temperature integration is involved in the plasticity of behavioral outputs.
Mice Create What–Where–When Hippocampus-Dependent Memories of Unique Experiences
Authors: Fellini Laetitia , Morellini Fabio
Published: January 2013

Episodic memory is relevant for auto-consciousness in humans. In nonhuman animals, episodic-like memory is defined when the “what–where–when” content of a unique event forms an integrated cognitive representation that is then deployed during memory retrieval. Here, we aimed at testing episodic-like memories of mice under experimental conditions that allow the analysis of whether and how mice process what–where–when information. Using an ecologically relevant paradigm for spontaneous learning and memory, we show that mice modulate their behavior based on the what, where, and when components of past unique episodes, specifically on previous encounters of conspecifics at a defined location and at a specific time of the day. We also show that learning during this paradigm activatedArc/Arg3.1mRNA expression in the hippocampus and that stereotactic injection of anisomycin into this region impairs memory consolidation. Thus, hippocampus-dependent episodic-like memories of single experiences are spontaneously created in mice. These findings extend our knowledge of the cognitive capacities of the mouse and suggest that this species can be used as model for studying the mechanisms underlying human episodic memory and related neurological disorders.
Prenatal Stress Induces Schizophrenia-Like Alterations of Serotonin 2A and Metabotropic Glutamate 2 Receptors in the Adult Offspring: Role of Maternal Immune System
Authors: Holloway Terrell , Moreno José L. , Umali Adrienne , Rayannavar Vinayak , Hodes Georgia E. , Russo Scott J. , González-Maeso Javier
Published: January 2013

It has been suggested that severe adverse life events during pregnancy increase the risk of schizophrenia in the offspring. The serotonin 5-HT2Aand the metabotropic glutamate 2 (mGlu2) receptors both have been the target of considerable attention regarding schizophrenia and antipsychotic drug development. We tested the effects of maternal variable stress during pregnancy on expression and behavioral function of these two receptors in mice. Prenatal stress increased 5-HT2Aand decreased mGlu2 expression in frontal cortex, a brain region involved in perception, cognition, and mood. This pattern of expression of 5-HT2Aand mGlu2 receptors was consistent with behavioral alterations, including increased head-twitch response to the hallucinogenic 5-HT2Aagonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] and decreased mGlu2-dependent antipsychotic-like effect of the mGlu2/3 agonist LY379268 (1R,4R,5S,6R-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate) in adult, but not prepubertal, mice born to stressed mothers during pregnancy. Cross-fostering studies determined that these alterations were not attributable to effects of prenatal stress on maternal care. Additionally, a similar pattern of biochemical and behavioral changes were observed in mice born to mothers injected with polyinosinic:polycytidylic acid [poly(I:C)] during pregnancy as a model of prenatal immune activation. These data strengthen pathophysiological hypotheses that propose an early neurodevelopmental origin for schizophrenia and other psychiatric disorders.
Coaxial Anisotropy of Cortical Point Spread in Human Visual Areas
Authors: Park Soo Hyun , Cha Kuwook , Lee Sang-Hun
Published: January 2013

A focal stimulus triggers neural activity that spreads to cortical regions far beyond the stimulation site, creating a so-called “cortical point spread” (CPS). Animal studies found that V1 neurons possess lateral connections with neighboring neurons that prefer similar orientations and to neurons representing visuotopic regions that are constrained by their preferred orientation axis. Although various roles in visual processing are proposed for this anatomical anisotropy of lateral connections, evidence for a corresponding “functional” anisotropy in CPS is lacking or inconsistent in animal studies and absent in humans. To explore functional anisotropy, we inspected axial constraints on CPS in human visual cortex using functional magnetic resonance imaging. We defined receptive fields (RFs) of unit gray matter volumes and delineated the spatial extents of CPS in visuotopic space. The CPS triggered by foveal stimuli exhibited coaxial anisotropy with larger spatial extents along the axis of stimulus orientation. Furthermore, the spatial extents of CPS along the coaxial direction increased with an increasing similarity of local sites to the CPS-inducing stimulus in orientation preference. From CPS driven by multifocal stimuli, the coaxially biased spread was also found in cortical regions in the periphery, albeit reduced in degree, and was invariant to a varying degree of radial relationship between stimuli and RF positions of local sites, rejecting radial bias as an origin of coaxial anisotropy. Our findings provide a bridge between the anatomical anisotropy seen in animal visual cortex and a possible network property supporting spatial contextual effects in human visual perception.
Adolescent Morphine Exposure Affects Long-Term Microglial Function and Later-Life Relapse Liability in a Model of Addiction
Authors: Schwarz Jaclyn M. , Bilbo Staci D.
Published: January 2013

Adolescence in humans represents a unique developmental time point associated with increased risk-taking behavior and experimentation with drugs of abuse. We hypothesized that exposure to drugs of abuse during adolescence may increase the risk of addiction in adulthood. To test this, rats were treated with a subchronic regimen of morphine or saline in adolescence, and their preference for morphine was examined using conditioned place preference (CPP) and drug-induced reinstatement in adulthood. The initial preference for morphine did not differ between groups; however, rats treated with morphine during adolescence showed robust reinstatement of morphine CPP after drug re-exposure in adulthood. This effect was not seen in rats pretreated with a subchronic regimen of morphine as adults, suggesting that exposure to morphine specifically during adolescence increases the risk of relapse to drug-seeking behavior in adulthood. We have previously established a role for microglia, the immune cells of the brain, and immune molecules in the risk of drug-induced reinstatement of morphine CPP. Thus, we examined the role of microglia within the nucleus accumbens of these rats and determined that rats exposed to morphine during adolescence had a significant increase in Toll-like receptor 4 (TLR4) mRNA and protein expression specifically on microglia. Morphine binds to TLR4 directly, and this increase in TLR4 was associated with exaggerated morphine-induced TLR4 signaling and microglial activation in rats previously exposed to morphine during adolescence. These data suggest that long-term changes in microglial function, caused by adolescent morphine exposure, alter the risk of drug-induced reinstatement in adulthood.