bluuebunny/crossref_metadata_2025 huggingface dataset:
The Maintenance of Cisplatin- and Paclitaxel-Induced Mechanical and Cold Allodynia is Suppressed by Cannabinoid CB2 Receptor Activation and Independent of CXCR4 Signaling in Models of Chemotherapy-Induced Peripheral Neuropathy
Authors: Deng Liting , Guindon Josée , Vemuri V Kiran , Thakur Ganesh A , White Fletcher A , Makriyannis Alexandros , Hohmann Andrea G
Published: September 2012

Background:

Chemotherapeutic agents produce dose-limiting peripheral neuropathy through mechanisms that remain poorly understood. We previously showed that AM1710, a cannabilactone 2 agonist, produces antinociception without producing central nervous system (CNS)-associated side effects. The present study was conducted to examine the antinociceptive effect of AM1710 in rodent models of neuropathic pain evoked by diverse chemotherapeutic agents (cisplatin and paclitaxel). A secondary objective was to investigate the potential contribution of alpha-chemokine receptor (CXCR4) signaling to both chemotherapy-induced neuropathy and CB2 agonist efficacy.

Results:

AM1710 (0.1, 1 or 5 mg/kg i.p.) suppressed the maintenance of mechanical and cold allodynia in the cisplatin and paclitaxel models. Anti-allodynic effects of AM1710 were blocked by the CB2 antagonist AM630 (3 mg/kg i.p.), but not the CB1 antagonist AM251 (3 mg/kg i.p.), consistent with a CB2-mediated effect. By contrast, blockade of CXCR4 signaling with its receptor antagonist AMD3100 (10 mg/kg i.p.) failed to attenuate mechanical or cold hypersensitivity induced by either cisplatin or paclitaxel. Moreover, blockade of CXCR4 signaling failed to alter the anti-allodynic effects of AM1710 in the paclitaxel model, further suggesting distinct mechanisms of action.

Conclusions:

Our results indicate that activation of cannabinoid CB2 receptors by AM1710 suppresses both mechanical and cold allodynia in two distinct models of chemotherapy-induced neuropathic pain. By contrast, CXCR4 signaling does not contribute to the maintenance of chemotherapy-induced established neuropathy or efficacy of AM1710. Our studies suggest that CB2 receptors represent a promising therapeutic target for the treatment of toxic neuropathies produced by cisplatin and paclitaxel chemotherapeutic agents.
Individual Cognitive Stimulation Therapy for dementia (iCST): study protocol for a randomized controlled trial
Authors: Orrell Martin , Yates Lauren A , Burns Alistair , Russell Ian , Woods Robert T , Hoare Zoe , Moniz-Cook Esme , Henderson Catherine , Knapp Martin , Spector Aimee , Orgeta Vasiliki
Published: September 2012

Background

Improving the quality of care for people with dementia and their carers has become a national priority in many countries. Cognitive Stimulation Therapy (CST) groups can be beneficial in improving cognition and quality of life for people with dementia. The aim of the current study is to develop and evaluate a home-based individual Cognitive Stimulation Therapy (iCST) programme for people with dementia which can be delivered by their family carer.

Methods

This multi-centre, pragmatic randomised controlled trial (RCT) will compare the effectiveness and cost-effectiveness of iCST for people with dementia with a treatment as usual control group. The intervention consists of iCST sessions delivered by a carer for 30 minutes, 3 times a week over 25 weeks.

For people with dementia the primary outcome measures are cognition assessed by the ADAS-Cog, and quality of life assessed by QoL-AD. For carers, quality of life using the SF-12 is the primary outcome measure. Using a 5% significance level, comparison of 306 participants will yield 80% power to detect an effect size of 0.35 for cognition as measured by the ADAS-Cog, and quality of life as measured by the QoL-AD. Quality of life for the carer will be measured using the SF-12. The trial will include a cost-effectiveness analysis from a public sector perspective.

Discussion

The UK Department of Health has recently stressed that improving access to psychological therapies is a national priority, but many people with dementia are unable to access psychological interventions. The development of a home-based individual version of CST will provide an easy to use, widely available therapy package that will be evaluated for effectiveness and cost-effectiveness in a multi centre RCT.
Primary mesenchymal chondrosarcoma of the kidney with synchronous implant and infiltrating urothelial carcinoma of the ureter
Authors: Xu Hua , Shao MuMin , Sun HuiLi , Li ShunMin
Published: September 2012

Primary mesenchymal chondrosarcoma of the kidney is rare, and it shows distinct undifferentiated tumor cells and well differentiated cartilagenous components. Also assident infiltrating urothelial carcinoma of the ureter is an extremely rare cancer. We report a case of primary mesenchymal chondrosarcoma occurring in the left kidney with an ipsilateral and distinct distal ureteric implant, and a coexisting infiltrating urothelial carcinoma of the ureter in a 64-year-old man. Histopathological examination and immunohistochemical studuies showed the classic features of mesenchymal chondrosarcoma in kidney, as well as a few infiltrating urothelial in ureter. Multitarget fluorescence in situ hybridization (FISH) suggested that the development of the urothelial carcinoma in the ureter may be triggered or induced by the chondrosarcoma component. The patient died 2 month after left nephro-ureterectomy. This is the first reported case of a primary mesenchymal chondrosarcoma of the kidney with coexisting infiltrating urothelial carcinoma of the ureter.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1522835667751019
BLV-CoCoMo-qPCR: a useful tool for evaluating bovine leukemia virus infection status
Authors: Jimba Mayuko , Takeshima Shin-nosuke , Murakami Hironobu , Kohara Junko , Kobayashi Naohiko , Matsuhashi Tamako , Ohmori Takashi , Nunoya Tetsuo , Aida Yoko
Published: September 2012

Background

Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis, which is the most common neoplastic disease of cattle. BLV infects cattle worldwide, imposing a severe economic impact on the dairy cattle industry. Recently, we developed a new quantitative real-time polymerase chain reaction (PCR) method using Coordination of Common Motifs (CoCoMo) primers to measure the proviral load of known and novel BLV variants in BLV-infected animals. Indeed, the assay was highly effective in detecting BLV in cattle from a range of international locations. This assay enabled us to demonstrate that proviral load correlates not only with BLV infection capacity as assessed by syncytium formation, but also with BLV disease progression. In this study, we compared the sensitivity of our BLV-CoCoMo-qPCR method for detecting BLV proviruses with the sensitivities of two real-time PCR systems, and also determined the differences of proviral load with serotests.

Results

BLV-CoCoMo-qPCR was found to be highly sensitive when compared with the real-time PCR-based TaqMan MGB assay developed by Lewet al. and the commercial TaKaRa cycleave PCR system. The BLV copy number determined by BLV-CoCoMo-qPCR was only partially correlated with the positive rate for anti-BLV antibody as determined by the enzyme-linked immunosorbent assay, passive hemagglutination reaction, or agar gel immunodiffusion. This result indicates that, although serotests are widely used for the diagnosis of BLV infection, it is difficult to detect BLV infection with confidence by using serological tests alone. Two cattle were experimentally infected with BLV. The kinetics of the provirus did not precisely correlate with the change in anti-BLV antibody production. Moreover, both reactions were different in cattle that carried different bovine leukocyte antigen (BoLA)-DRB3 genotypes.

Conclusions

Our results suggest that the quantitative measurement of proviral load by BLV-CoCoMo-qPCR is useful tool for evaluating the progression of BLV-induced disease. BLV-CoCoMo-qPCR allows us to monitor the spread of BLV infection in different viewpoint compared with classical serotest.
Isolation and characterization of ovine mesenchymal stem cells derived from peripheral blood
Authors: Lyahyai Jaber , Mediano Diego R , Ranera Beatriz , Sanz Arianne , Remacha Ana Rosa , Bolea Rosa , Zaragoza Pilar , Rodellar Clementina , Martín-Burriel Inmaculada
Published: September 2012

Background

Mesenchymal stem cells (MSCs) are multipotent stem cells with capacity to differentiate into several mesenchymal lineages. This quality makes MSCs good candidates for use in cell therapy. MSCs can be isolated from a variety of tissues including bone marrow and adipose tissue, which are the most common sources of these cells. However, MSCs can also be isolated from peripheral blood. Sheep has been proposed as an ideal model for biomedical studies including those of orthopaedics and transmissible spongiform encephalopathies (TSEs). The aim of this work was to advance these studies by investigating the possibility of MSC isolation from ovine peripheral blood (oPB-MSCs) and by subsequently characterizing there in vitro properties.

Results

Plastic-adherent fibroblast-like cells were obtained from the mononuclear fraction of blood samples. These cells were analysed for their proliferative and differentiation potential into adipocytes, osteoblasts and chondrocytes, as well as for the gene expression of cell surface markers. The isolated cells expressed transcripts for markers CD29, CD73 and CD90, but failed to express the haematopoietic marker CD45 and expressed only low levels of CD105. The expression of CD34 was variable. The differentiation potential of this cell population was evaluated using specific differentiation media. Although the ability of the cultures derived from different animals to differentiate into adipocytes, osteoblasts and chondrocytes was heterogeneous, we confirmed this feature using specific staining and analysing the gene expression of differentiation markers. Finally, we tested the ability of oPB-MSCs to transdifferentiate into neuronal-like cells. Morphological changes were observed after 24-hour culture in neurogenic media, and the transcript levels of the neurogenic markers increased during the prolonged induction period. Moreover, oPB-MSCs expressed the cellular prion protein gene (PRNP), which was up-regulated during neurogenesis.

Conclusions

This study describes for the first time the isolation and characterization of oPB-MSCs. Albeit some variability was observed between animals, these cells retained their capacity to differentiate into mesenchymal lineages and to transdifferentiate into neuron-like cells in vitro
. Therefore, oPB-MSCs could serve as a valuable tool for biomedical research in fields including orthopaedics or prion diseases.
Exploring the reach and program use of hello world, an email-based health promotion program for pregnant women in the Netherlands
Authors: van Dongen Johanna M , van Poppel Mireille NM , Milder Ivon EJ , van Oers Hans AM , Brug Johannes
Published: September 2012

Background

In 2006, the Dutch government initiated Hello World, an email-based program promoting healthy lifestyles among pregnant women through quizzes with pregnancy-related questions. In 2008, an updated version was released.

The present study aimed to (1) examine the reach of Hello World and the representativeness of its users for all pregnant women in the Netherlands, (2) explore the relationship between program engagement and lifestyle characteristics, and (3) explore the relationship between the program content participants accessed (content on smoking, physical activity, and nutrition) and their lifestyle characteristics.

Methods

Data from 4,363 pregnant women were included. After registration, women received an online questionnaire with demographic and lifestyle questions. To evaluate their representativeness, their demographic characteristics were compared with existing data for Dutch (pregnant) women. Women were classified on the following lifestyle characteristics: smoking, nutrition, physical activity, and pre-pregnancy weight status. Program use was tracked and the relationships between lifestyle characteristics, program engagement, and the percentage of smoking, physical activity, and nutrition questions accessed after opening a quiz were explored using Mann–Whitney U tests and Kruskal-Wallis tests.

Results

Hello World reached ±4% of its target population. Ten percent of participants were low educated and 22% immigrants. On average, women received 6.1 (SD:2.8) quiz emails and opened 32% of the associated quizzes (2.0, SD:2.1). A significant positive association was found between the number of quizzes opened and the number of healthy lifestyle characteristics. After opening a quiz, women accessed most smoking, nutrition, and physical activity questions. Significant relationships were found between several lifestyle characteristics and the percentage of smoking, physical activity, and nutrition questions accessed. However, between-group differences were small, quiz topics were largely unrelated to their lifestyle characteristics, and inconsistencies were found regarding the directions of these associations.

Conclusions

Hello World reached ±4% of its target population, which is lower than the reach of its previous version (±8%). Relatively few low educated and immigrant women registered for the program. Active participation in the program was positively associated with the number of healthy behaviours participants engaged in. The program content participants chose to access was largely unrelated to their lifestyle characteristics.
Multimodality cardiac imaging of a double chambered right ventricle with intrapulmonary shunting: a case report
Authors: Kha Lan-Chau , Cassano-Bailey Alessandra , Cleverley Kelby , Sud Maneesh , Strzelczyk Jacek , Jassal Davinder S
Published: September 2012

Background

Double chambered right ventricle (DCRV) is a relatively rare congenital heart disease, characterized by the abnormal division of the right ventricle into a high-pressure inlet and low-pressure outlet by anomalous muscle bundles. Extra-cardiac right-to-left shunts may present with clinical symptoms in adulthood and should be sought in patients with previous cavo-pulmonary shunt procedures.

Case presentation

We report a case of DCRV in a 29 year old Caucasian male presenting in adulthood with a right-to-left shunt secondary to venous collaterals, following cavopulmonary anastomosis for congenital pulmonary atresia and hypoplastic right ventricle.

Conclusion

Multimodality cardiac imaging using echocardiography, cardiac CT, cardiac MRI and cardiac catheterization is often required for complete characterization of complex congenital heart anomalies in adulthood.
Salmonella in meats, water, fruit and vegetables as disclosed from testing undertaken by Food Business Operators in Ireland from 2005 to 2009
Authors: Duggan Sharon , Jordan Emily , Gutierrez Montserrat , Barrett Gaye , O’Brien Tony , Hand Darren , Kenny Kevin , Fanning June , Leonard Nola , Egan John
Published: September 2012

Food Business Operators (FBO) are responsible for the safety of the food they produce and in Ireland those under the regulatory control of the Department of Agriculture, Food and Marine are required to provide summary data on microbiological tests undertaken as part of their food safety controls. These data are provided to the National Reference Laboratory through the 25 private laboratories undertaking the testing.

Results

Over the five-year period Salmonella sp. was isolated from 0.7% of the 254,000 raw meat or raw meat products tested with the annual prevalence ranging from 0.5 to 1.1%. Poultry meats were consistently more contaminated than other meats with higher recovery rates in turkey (3.3%), duck (3.3%), and chicken (2.5%) compared with meats of porcine (1.6%), ovine (0.2%) and bovine origin (0.1%). Salmonella sp. was also isolated from 58 (0.06%) of the 96,115 cooked or partially cooked meat and meat products tested during the reporting period with the annual percentage positive samples ranging from 0.01 to 0.16%. A total of 50 different serotypes were recovered from raw meats over this period with the greatest diversity found in poultry samples (n = 36). Four serotypes, Kentucky, Typhimurium, Agona and Derby accounted for over 70% of all isolates detected on FBO testing over the period 2005 to 2009.

Conclusions

Capturing microbiological data generated by Food Business Operators allows the regulatory sector access to a substantial amount of valuable data with the minimum financial outlay.
Development of an effective risk management system in a teaching hospital
Authors: Adibi Hossein , Khalesi Nader , Ravaghi Hamid , Jafari Mahdi , Jeddian Ali Reza
Published: September 2012

Background

Unsafe health care provision is a main cause of increased mortality rate amongst hospitalized patients all over the world. A system approach to medical error and its reduction is crucial that is defined by clinical and administrative activities undertaken to identify, evaluate, and reduce the risk of injury. The aim of this study was to develop and implement a risk management system in a large teaching hospital in Iran, especially of the basis of WHO guidelines and patient safety context.

Methods

WHO draft guideline and patient safety reports from different countries were reviewed for defining acceptable framework of risk management system. Also current situation of mentioned hospital in safety matter and dimensions of patient safety culture was evaluated using HSOPSC questionnaire of AHRQ. With adjustment of guidelines and hospital status, the conceptual framework was developed and next it was validated in expert panel. The members of expert panel were selected according to their role and functions and also their experiences in risk management and patient safety issues. The validated framework consisted of designating a leader and coordinator core, defining communications, and preparing the infrastructure for patient safety education and culture-building. That was developed on the basis of some values and commitments and included reactive and proactive approaches.

Results

The findings of reporting activities demonstrated that at least 3.6 percent of hospitalized patients have experienced adverse events and 5.3 percent of all deaths in the hospital related with patient safety problems. Beside the average score of 12 dimensions of patient safety culture was 46.2 percent that was considerably low. The “non-punitive responses to error” had lowest positive score with 21.2 percent.

Conclusion

It is of paramount importance for all health organizations to lay necessary foundations in order to identify safety risks and improve the quality of care. Inadequate participation of staff in education, reporting and analyzing, underreporting and uselessness of aggregated data, limitation of human and financial resources, punitive directions and management challenges for solutions were the main executive problems which could affect the effectiveness of system.
Ablation of Leptin Signaling to Somatotropes: Changes in Metabolic Factors that Cause Obesity
Authors: Akhter Noor , Odle Angela K. , Allensworth-James Melody L. , Haney Anessa C. , Syed Mohsin M. , Cozart Michael A. , Chua Streamson , Kineman Rhonda , Childs Gwen V.
Published: September 2012

Mice with somatotrope-specific deletion of the Janus kinase binding site in leptin receptors are GH deficient as young adults and become obese by 6 months of age. This study focused on the metabolic status of young (3–4.5 month old) preobese mutant mice. These mutants had normal body weights, lean body mass, serum leptin, glucose, and triglycerides. Mutant males and females showed significantly higher respiratory quotients (RQ) and lower energy output, resulting from a higher volume of CO2 output and lower volume of O2 consumption. Deletion mutant females were significantly less active than controls; they had higher levels of total serum ghrelin and ate more food. Mutant females also had lower serum insulin and higher glucagon. In contrast, deletion mutant males were not hyperphagic, but they were more active and spent less time sleeping. Adiponectin and resistin, both products of adipocytes, were increased in male and female mutant mice. In addition, mutant males showed an increase in circulating levels of the potent lipogenic hormone, glucose-dependent insulinotropic peptide. Taken together, these results indicate that mutant mice may become obese due to a reduction in lipid oxidation and energy expenditure. This may stem from GH deficiency. Reduced fat oxidation and enhanced insulin sensitivity (in females) are directly related to GH deficiency in mutant mice because GH has been shown by others to increase insulin sensitivity and fat oxidation and reduce carbohydrate oxidation. Gender-dependent alterations in metabolic signals may further exacerbate the future obese phenotype and affect the timing of its onset. Females show a delay in onset of obesity, perhaps because of their low serum insulin, which is lipogenic, whereas young males already have higher levels of the lipogenic hormone, glucose-dependent insulinotropic peptide. These findings signify that leptin signals to somatotropes are vital for the normal metabolic activity needed to optimize body composition.
Cross Talk between PKC and CREB in the Induction of COX-2 by PGF2α in Human Amnion Fibroblasts
Authors: Guo C. M. , Kasaraneni N. , Sun K. , Myatt L.
Published: September 2012

Compelling evidence indicates a crucial role of prostaglandin F2α (PGF2α) in parturition. Both the maternal and fetal sides of the fetal membranes synthesize PGF2α, which exerts effects via the prostaglandin F2α receptor (FP) that is coupled to the activation of protein kinase C (PKC). Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step of the inducible synthesis of prostaglandin. Although activation of PKC is known to induce COX-2 expression, it is not clear whether PGF2α can induce COX-2 via FP receptor-coupled PKC activation. COX-2 promoter carries a cAMP-response element (CRE) and phosphorylation of CRE binding protein 1 (CREB1) is associated with COX-2 expression in human amnion fibroblasts. We demonstrated that human amnion fibroblasts produced PGF2α and expressed FP receptor. PGF2α increased COX-2 expression and CREB1 phosphorylation, which could be blocked by either the FP receptor antagonist AL8810 or PKC inhibitor Ro31-7549. The PKC activator, phorbol-12-myristate-13-acetate (PMA), could mimic the induction of COX-2 and CREB1 phosphorylation. The induction of COX-2 by PGF2α and PMA could be attenuated by the small interfering RNA-mediated knockdown of CREB1 expression or overexpressing dominant-negative CREB1. A chromatin immunoprecipitation assay showed that the binding of CREB1 to the COX-2 promoter was increased by PGF2α and PMA in amnion fibroblasts. In conclusion, we provide evidence that PGF2α induces COX-2 expression via the FP receptor and phosphorylates CREB1 by PKC, thus increasing CREB1 binding to the COX-2 promoter and the expression of COX-2 in human amnion fibroblasts. This feed-forward loop may be crucial for the production of prostaglandins in the fetal membranes prior to the onset of labor.
Regulation of Estradiol and Progesterone Production by CRH-R1 and -R2 Is through Divergent Signaling Pathways in Cultured Human Placental Trophoblasts
Authors: Gao Lu , Tao Yi , Hu Tianxiao , Liu Weina , Xu Chen , Liu Jie , You Xingji , Gu Hang , Ni Xin
Published: September 2012

CRH and its related peptides urocortins (UCN) have been identified in placenta and implicated to play pivotal roles in the regulation of pregnancy and parturition in humans. The objectives of present study were to investigate the effects of endogenous CRH and its related peptides in the regulation of steroid production in placenta. Placental trophoblasts were isolated from term placenta tissues and cultured for 72 h. Estradiol (E2) and progesterone (P4) contents in culture media were determined by radioimmunoassay. Treatment of cultured trophoblasts with CRH or UCNI antibody showed decreased E2, whereas increased P4 production. Treatment of cells with CRH receptor type 1 antagonist antalarmin or CRH receptor type 2 (CRH-R2) antagonist astressin-2b also decreased E2 but increased P4 production. Knockdown of CRH receptor type 1 or CRH-R2 cells showed a decrease in E2 production and an increase in P4 production. In CRH-R2 knockdown cells, CRH stimulated GTP-bound Gαs protein and phosphorylated phospholipase C-β3. Adenylyl cyclase and protein kinase A inhibitors blocked CRH-induced increased E2 production but not decreased P4 production. PLC inhibitor U73122 and protein kinase C inhibitor chelerythrine blocked the effects of CRH on E2 and P4 production in CRH-R2 knockdown cells. UCNIII, the specific CRH-R2 agonist, stimulated GTP-bound Gαi protein and phosphorylated phospholipase C-β3 expression. Both U73122 and chelerythrine blocked UCNIII-induced increased E2 production and decreased P4 production. We suggest that CRH and its related peptides might be involved in changes in the progesterone to estrogen ratio during human pregnancy.
The Organizational and Aromatization Hypotheses Apply to Rapid, Nonclassical Hormone Action: Neonatal Masculinization Eliminates Rapid Estradiol Action in Female Hippocampal Neurons
Authors: Meitzen John , Grove Danielle D. , Mermelstein Paul G.
Published: September 2012

Early exposure to the steroid sex hormone testosterone and its estrogen metabolite estradiol masculinize neural tissue during a developmental critical period. Many aspects of neuron anatomy and physiology are permanently altered, including later sensitivity to estradiol. Although it is well established that early hormone exposure alters neuronal responsiveness regarding classical estradiol actions (i.e. acting via nuclear estrogen receptors), it has not yet been determined whether it also alters neuronal processing of nonclassical estrogen receptor signaling, including the actions of membrane-associated estrogen receptors. Hence, we tested whether membrane estrogen receptor regulation of cAMP response element binding protein (CREB) phosphorylation observed in female (but not male) hippocampal pyramidal neurons is due to the lack of androgen and/or estrogen exposure in females during this critical period. Female rat neonates on postnatal d 0 and 1 were systemically injected with one of four compounds: vehicle, testosterone, the nonaromatizable androgen dihydrotestosterone, or estradiol. On postnatal d 2, primary hippocampal neuron cultures were generated from these animals. After 8–9 d in culture, we assessed whether estradiol affected CREB phosphorylation. Neurons from female neonates exposed to testosterone lacked estradiol signaling to CREB. In contrast, dihydrotestosterone injections of female neonates did not disrupt estradiol regulation of CREB. Estradiol injections of female neonates, however, eliminated estradiol signaling to CREB. These findings indicate that testosterone aromatization to estradiol leads to a masculinization/defeminization process whereby hippocampal neurons fail to exhibit rapid estradiol signaling to CREB. Broadly, these findings extend the organizational and aromatization hypotheses to rapid, nonclassical hormone action.
Low Degree of Overlap Between Kisspeptin, Neurokinin B, and Dynorphin Immunoreactivities in the Infundibular Nucleus of Young Male Human Subjects Challenges the KNDy Neuron Concept
Authors: Hrabovszky Erik , Sipos Máté T. , Molnár Csilla S. , Ciofi Philippe , Borsay Beáta Á. , Gergely Péter , Herczeg László , Bloom Stephen R. , Ghatei Mohammad A. , Dhillo Waljit S. , Liposits Zsolt
Published: September 2012

Previous immunohistochemical and in situ hybridization studies of sheep, goats, and rodents indicated that kisspeptin (KP), neurokinin B (NKB), and dynorphin A (DYN) are extensively colocalized in the hypothalamic arcuate nucleus, thus providing a basis for the KP/NKB/DYN (KNDy) neuron concept; in both sexes, KNDy neuropeptides have been implicated in the generation of GnRH neurosecretory pulses and in the negative feedback effects of sexual steroids to the reproductive axis. To test the validity and limitations of the KNDy neuron concept in the human, we carried out the comparative immunohistochemical analysis of the three neuropeptides in the infundibular nucleus (Inf; also known as arcuate nucleus) and stalk of young male human individuals (<37 yr). Results of quantitative immunohistochemical experiments established that the regional densities of NKB immunoreactive (IR) perikarya and fibers, and the incidence of afferent contacts they formed onto GnRH neurons, were about 5 times as high as those of the KP-IR elements. Dual-immunofluorescent studies confirmed that considerable subsets of the NKB-IR and KP-IR cell bodies and fibers are separate, and only about 33% of NKB-IR perikarya and 75% of KP-IR perikarya were dual labeled. Furthermore, very few DYN-IR cell bodies could be visualized in the Inf. DYN-IR fibers were also rare and, with few exceptions, distinct from the KP-IR fibers. The abundance and colocalization patterns of the three immunoreactivities showed similar trends in the infundibular stalk around portal blood vessels. Together these results indicate that most NKB neurons in the Inf do not synthesize detectable amounts of KP and DYN in young male human individuals. These data call for a critical use of the KNDy neuron terminology when referring to the putative pulse generator system of the mediobasal hypothalamus. We conclude that the functional importance of these three neuropeptides in reproductive regulation considerably varies among species, between sexes, and at different ages.
Monasticism and the Public Contemplative in Late Medieval England: Richard Methley and His Spiritual Formation
Authors: Zieman Katherine
Published: September 2012

This essay explores the late medieval rhetoric of self-representation and conceptions of audience through an examination of the writings of the fifteenth-century Carthusian monk Richard Methley. Methley is considered as a “public contemplative” — a writer who offers his own contemplative experiences to a greater audience. Because these experiences, unlike visions, involved embodied ecstasies that are inseparable from the contemplative who experiences them, communicating them involved narrating the self as well as the experience. Methley’s position as a Carthusian, simultaneously solitary hermit and communal monk, allowed him to explore the possible relations between self and community. The essay demonstrates Methley’s self-conscious construction of his first-person narration by comparing and constrasting it to one of his most influential models, the fourteenth-century hermit, Richard Rolle, as well as to materials from vernacular traditions — the keeping of spiritual diaries promoted by the Devotio Moderna and the English text of The Cloud of Unknowing.
Applicability of the doubly labelled water method to the rhinoceros auklet, Cerorhinca monocerata
Authors: Shirai Masaki , Ito Motohiro , Yoda Ken , Niizuma Yasuaki
Published: September 2012

The doubly labelled water (DLW) method is an isotope-based technique that is used to measure the metabolic rates of free-living animals. We validated the DLW method for measuring metabolic rates in five rhinoceros auklets (Cerorhinca monocerata) compared with simultaneous measurements using the respirometric method. We calculated the CO2 production rate of four auklets (mean initial body mass: 552 g±36 s.d.) injected with DLW, using the one- and two-pool models. The metabolic rate during the 24-h measurements in a respirometric chamber for resting auklets averaged 16.30±1.66 kJ h−1 (n = 4). The metabolic rates determined using the one- and two-pool models in the DLW method for the same period as the respirometric measurement averaged 16.61±2.13 kJ h−1 (n = 4) and 16.16±2.10 kJ h−1 (n = 4), respectively. The mean absolute percent error between the DLW and respirometric methods was 8.04% using the one-pool model and was slightly better than that with the two-pool model. The differences in value between the DLW and respirometric methods are probably due to oxygen isotope turnover, which eliminated only 10–14% of the initial enrichment excess.
Chicken primordial germ cells use the anterior vitelline veins to enter the embryonic circulation
Authors: De Melo Bernardo Ana , Sprenkels Kaylee , Rodrigues Gabriela , Noce Toshiaki , Chuva De Sousa Lopes Susana M.
Published: September 2012

During gastrulation, chicken primordial germ cells (PGCs) are present in an extraembryonic region of the embryo from where they migrate towards the genital ridges. This is also observed in mammals, but in chicken the vehicle used by the migratory PGCs is the vascular system. We have analysed the migratory pathway of chicken PGCs, focusing on the period of transition from the extraembryonic region to the intraembryonic vascular system.

Our findings show that at Hamburger and Hamilton developmental stage HH12–HH14 the majority of PGCs concentrate axially in the sinus terminalis and favour transport axially via the anterior vitelline veins into the embryonic circulation. Moreover, directly blocking the blood flow through the anterior vitelline veins resulted in an accumulation of PGCs in the anterior region and a decreased number of PGCs in the genital ridges. We further confirmed the key role for the anterior vitelline veins in the correct migration of PGCs using an ex ovo culture method that resulted in defective morphogenetic development of the anterior vitelline veins.

We propose a novel model for the migratory pathway of chicken PGCs whereby the anterior vitelline veins play a central role at the extraembryonic and embryonic interface. The chicken model of PGC migration through the vasculature may be a powerful tool to study the process of homing (inflammation and metastasis) due to the striking similarities in regulatory signaling pathways (SDF1–CXCR4) and the transient role of the vasculature.
The interrelationship between APC/C and Plk1 activities in centriole disengagement
Authors: Hatano Toshiyuki , Sluder Greenfield
Published: September 2012

Mother–daughter centriole disengagement, the necessary first step in centriole duplication, involves Plk1 activity in early mitosis and separase activity after APC/C activity mediates securin degradation. Plk1 activity is thought to be essential and sufficient for centriole disengagement with separase activity playing a supporting but non-essential role. In separase null cells, however, centriole disengagement is substantially delayed. The ability of APC/C activity alone to mediate centriole disengagement has not been directly tested. We investigate the interrelationship between Plk1 and APC/C activities in disengaging centrioles in S or G2 HeLa and RPE1 cells, cell types that do not reduplicate centrioles when arrested in S phase. Knockdown of the interphase APC/C inhibitor Emi1 leads to centriole disengagement and reduplication of the mother centrioles, though this is slow. Strong inhibition of Plk1 activity, if any, during S does not block centriole disengagement and mother centriole reduplication in Emi1 depleted cells. Centriole disengagement depends on APC/C–Cdh1 activity, not APC/C–Cdc20 activity. Also, Plk1 and APC/C–Cdh1 activities can independently promote centriole disengagement in G2 arrested cells. Thus, Plk1 and APC/C–Cdh1 activities are independent but slow pathways for centriole disengagement. By having two slow mechanisms for disengagement working together, the cell ensures that centrioles will not prematurely separate in late G2 or early mitosis, thereby risking multipolar spindle assembly, but rather disengage in a timely fashion only late in mitosis.
A role for Rap2 in recycling the extended conformation of LFA-1 during T cell migration
Authors: Stanley Paula , Tooze Sharon , Hogg Nancy
Published: September 2012

T lymphocytes make use of their major integrin LFA-1 to migrate on surfaces that express ICAM-1 such as blood vessels and inflamed tissue sites. How the adhesions are turned over in order to supply traction for this migration has not been extensively investigated. By following the fate of biotinylated membrane LFA-1 on T lymphocytes, we show in this study that LFA-1 internalization and re-exposure on the plasma membrane are linked to migration. Previously we demonstrated the GTPase Rap2 to be a regulator of LFA-1-mediated migration. SiRNA knockdown of this GTPase inhibits both LFA-1 internalization and also its ability to be re-exposed, indicating that Rap2 participates in recycling of LFA-1 and influences its complete endocytosis–exocytosis cycle. Confocal microscopy images reveal that the intracellular distribution of Rap2 overlaps with endosomal recycling vesicles. Although the homologous GTPase Rap1 is also found on intracellular vesicles and associated with LFA-1 activation, these two homologous GTPases do not co-localize. Little is known about the conformation of the LFA-1 that is recycled. We show that the extended form of LFA-1 is internalized and in Rap2 siRNA-treated T lymphocytes the trafficking of this LFA-1 conformation is disrupted resulting in its intracellular accumulation. Thus LFA-1-mediated migration of T lymphocytes requires Rap2-expressing vesicles to recycle the extended form of LFA-1 that we have previously found to control migration at the leading edge.
Apoptosis ofAscogregarina taiwanensis(Apicomplexa: Lecudinidae) which failed to migrate within its natural host
Authors: Chen Wei-June , Huang Ching-Gi , Fan-Chiang Mei-Huei , Liu Yu-Han , Lee Yi-Feng
Published: September 2012

Sexual reproduction of Ascogregarina taiwanensis (Apicomplexa: Lecudinidae), a parasite specific to the mosquito Aedes albopictus, in malpighian tubules is initiated by the entry of the trophotozoites developed in the midgut shortly afterpupation (usually < 5 h). However, only a low proportion of trophozoites are able to migrate; others end up dying. In this study, we demonstrated those trophozoites which failed to migrate eventually died of apoptosis. Morphological changes such as shrinkage, chromatin aggregations, and formation of blunt ridges on the surface were seen in moribund trophozoites. In addition, DNA fragmentation of trophozoites isolated from the midgut of pupae was demonstrated by the presence of DNA ladders, Annexin V staining, and TUNEL assays. Due to detection of caspase-like activity, apoptosis of those trophozoites may have occurred through a mechanism of an intrinsic or mitochondrial-mediated pathway. Although apoptosis has been observed in various species of protozoa, it is not clear how apoptosis in single-celled organisms might result from evolution by natural selection. However, we speculate that apoptosis may regulate the parasite load of A. taiwanensis within its natural mosquito host, leading to an optimized state of the survival rate for both parasite and host.
Micro-, Meso-, and Macroporous Materials Obtained from a Highly Concentrated Emulsion of Decane/Brij 35/Water and Decane/Brij 700/Water
Authors: Santamaría Esther , Cortés Marta , Maestro Alicia , Porras Montserrat , Gutiérrez Jose Maria , González Carmen
Published: September 2012

Mesoporous materials have high potential for use as catalyst supports. Different formation mechanisms for mesostructured materials have already been described. In the present study, different micro-, meso-, and macroporous materials were obtained from highly concentrated emulsions, and the possibility of raw materials recovery was investigated. The materials, including that synthesized from a recovered surfactant, were tested as Nafion catalyst supports. Moreover, ordered mesoporous materials were obtained through another formation mechanism, namely, cooperative autoassembling, and the influence of the preparation and composition variables on the specific area of the materials was studied.
Cleavable Gemini Cationic Surfactants: Experimental and Theoretical Description of Adsorption
Authors: Wilk Kazimiera A , Frckowiak Renata , uczynski Jacek , Warszynski Piotr
Published: September 2012

The aim of the present study was to examine, both experimentally and theoretically, the interfacial behavior of cleavable gemini ester quat-type cationic surfactants in comparison to a standard gemini representative. For the theoretical description of the air/water surface tension isotherms of the corresponding geminis, a modified model of multiply charged ionic surfactant adsorption (surface quasi-two-dimensional electrolyte, STDE), taking into account counter ion specificity and formation of surfactant ion–counter-ion associates, was used. As a result, good agreement between theory and experiment was obtained.
Reliability of plasma fibroblast growth factor 23 as risk biomarker in epidemiological studies measured over a four-month period
Authors: di Giuseppe Romina , Hirche Frank , Montonen Jukka , Buijsse Brian , Dierkes Jutta , Stangl Gabriele I , Boeing Heiner , Weikert Cornelia
Published: September 2012

Background

Identified as a biomarker of altered calcium–phosphorus metabolism in chronic kidney disease, fibroblast growth factor 23 (FGF-23) can also be used as a biomarker of risk for cardiovascular disease in the general population. However, it is crucial to first evaluate the reproducibility (reliability) of plasma FGF-23 concentrations.

Methods

We assessed the reliability of plasma FGF-23 concentrations using replicate blood samples taken four months apart of 207 participants from the European Prospective Investigation into Cancer and Nutrition-Potsdam Study.

Results

Plasma FGF-23 concentrations at baseline (geometric mean: 24.7 RU/mL; 95% confidence interval [CI] in RU/mL: 21.8–27.9) were not significantly different from those measured four months later (geometric mean: 23.7 RU/mL; 95% CI in RU/mL: 20.6–27.1; P = 0.42). The intraclass correlation coefficients were 0.69 (95% CI: 0.62–0.76) for all; 0.64 (95% CI: 0.50–0.75) for men and 0.73 (95% CI: 0.64–0.81) for women.

Conclusions

Plasma FGF-23 concentrations showed good reliability over time. Our findings suggest that in epidemiological studies, a single plasma FGF-23 measurement may be sufficient to derive the relative risk in prospective cohort studies.
Opportunistic screening for familial hypercholesterolaemia via a community laboratory
Authors: Bell Damon A , Hooper Amanda J , Bender Robert , McMahon Jenny , Edwards Glenn , van Bockxmeer Frank M , Watts Gerald F , Burnett John R
Published: September 2012

Background

Familial hypercholesterolaemia (FH) is an inherited disorder characterized by increased serum low-density lipoprotein (LDL)-cholesterol concentrations and premature atherosclerotic cardiovascular disease. The majority of people with FH are currently undiagnosed. We sought to determine the ability of a community laboratory to screen for individuals with potential FH.

Methods

Serum LDL-cholesterol concentrations issued by a private community laboratory in Western Australia were reviewed over a one-year period (1 May 2010 to 31 April 2011). We assessed the prevalence of possible FH based on LDL-cholesterol thresholds employed by the Make Early Diagnosis-Prevent Early Death (MED-PED), the Simon Broome Registry and the Dutch Lipid Clinic Network criteria.

Results

During this period, 84,823 people had 99,467 serum LDL-cholesterol measurements, with 91.8% requested by general practitioners. A secondary cause of hypercholesterolaemia was identified in 8.3% of subjects with an LDL-cholesterol ≥5.0 mmol/L. The prevalence of FH based on an LDL-cholesterol ≥6.5 mmol/L, the 99.75th percentile, was 1:398 in this sample population; similarly, the MED-PED LDL-cholesterol criteria gave a prevalence of 1:482.

Conclusions

The community laboratory is well placed to screen opportunistically for subjects with potential FH. This may be achieved using either the MED-PED criteria or a serum LDL-cholesterol cut-off point of ≥6.5 mmol/L, irrespective of age. Further investigation is required to determine the most effective method of identifying these individuals and, thereby, ensuring referral to a specialist lipid clinic.
Baseline brain activity changes in patients with clinically isolated syndrome revealed by resting-state functional MRI
Authors: Liu Yaou , Duan Yunyun , Liang Peipeng , Jia Xiuqin , Yu Chunshui , Ye Jing , Butzkueven Helmut , Dong Huiqing , Li Kuncheng
Published: September 2012

Background

A clinically isolated syndrome (CIS) is the first manifestation of multiple sclerosis (MS). Previous task-related functional MRI studies demonstrate functional reorganization in patients with CIS.

Purpose

To assess baseline brain activity changes in patients with CIS by using the technique of regional amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI.

Material and Methods

Resting-state fMRIs data acquired from 37 patients with CIS and 37 age- and sex-matched normal controls were compared to investigate ALFF differences. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration, and T2 lesion volume (T2LV) were further explored.

Results

Patients with CIS had significantly decreased ALFF in the right anterior cingulate cortex, right caudate, right lingual gyrus, and right cuneus ( P < 0.05 corrected for multiple comparisons using Monte Carlo simulation) compared to normal controls, while no significantly increased ALFF were observed in CIS. No significant correlation was found between the EDSS, disease duration, T2LV, and ALFF in regions with significant group differences.

Conclusion

In patients with CIS, resting-state fMRI demonstrates decreased activity in several brain regions. These results are in contrast to patients with established MS, in whom ALFF demonstrates several regions of increased activity. It is possible that this shift from decreased activity in CIS to increased activity in MS could reflect the dynamics of cortical reorganization.
Mesenteric lipoma causing small bowel perforation: a case report and review of literature
Authors: watt D G , Sanjay P , Walsh S V , Young J A , Alijani A
Published: September 2012

A lipoma of the small bowel mesentery is a rare pathological entity. It has been shown to rarely cause obstruction and volvulus of the small bowel. We report a case of a 72-year-old man who presented with lower abdominal pain and slightly raised inflammatory markers. Computerized tomography of the abdomen showed small bowel perforation and oedematous terminal ileum. At laparotomy the cause was found to be a mesenteric lipoma causing small bowel perforation. As far as the authors are aware, this presentation is not described in the English language literature.