bluuebunny/crossref_metadata_2025 huggingface dataset:
A rare cause of severe hepatomegaly with an improving outcome
Authors: Godskesen Line , Abildgaard Niels , Kjeldsen Jens , Krag Aleksander
Published: April 2014

A previously healthy 43-year-old man presented with dyspnoea, 15 kg weight loss, severe hepatomegaly and alkaline phosphatase at 5400 U/L. Examinations seemed to suggest cirrhosis, but blood samples did not show any signs of underlying liver disease. Liver biopsy revealed amyloid light chain (AL) amyloidosis and bone marrow showed multiple myeloma (MM). The patient was treated with drugs of choice cyclophosphamide, bortezomib and dexamethasone. He responded well to the treatment and so far achieved partial response. Previously MM was associated with poor prognosis but due to improved treatment for AL the patient can achieve a progression-free period with good quality of life.
Not just a red eye
Authors: Juniat Valerie , Andrew Nigel
Published: April 2014

A 70-year-old woman presented to the Eye Casualty department with a 10-day history of worsening pain and redness in her right eye, associated with progressively reduced vision. History revealed that the patient had recently completed a course of chemotherapy for metastatic breast cancer. Anterior examination of the right eye revealed a vascularised iris mass causing pupillary distortion, intraocular inflammation and raised intraocular pressure. She was diagnosed with a right iris metastasis secondary to breast cancer. Ocular management consisted of topical steroids and intraocular pressure-lowering agents, which improved her ocular symptoms. She subsequently received primary radiotherapy, which has successfully reduced the size of the tumour.
‘Well London’ and the benefits of participation: results of a qualitative study nested in a cluster randomised trial
Authors: Derges Jane , Clow Angela , Lynch Rebecca , Jain Sumeet , Phillips Gemma , Petticrew Mark , Renton Adrian , Draper Alizon
Published: April 2014

Background

Well Londonis a multicomponent community engagement and coproduction programme designed to improve the health of Londoners living in socioeconomically deprived neighbourhoods. To evaluate outcomes of theWell Londoninterventions, a cluster randomised trial (CRT) was conducted that included a longitudinal qualitative component, which is reported here. The aim is to explore in depth the nature of the benefits to residents and the processes by which these were achieved.

Methods

The 1-year longitudinal qualitative study was nested within the CRT. Purposive sampling was used to select three intervention neighbourhoods in London and 61 individuals within these neighbourhoods. The interventions comprised activities focused on: healthy eating, physical exercise and mental health and well-being. Interviews were conducted at the inception and following completion of theWell Londoninterventions to establish both if and how they had participated. Transcripts of the interviews were coded and analysed using Nvivo.

Results

Positive benefits relating to the formal outcomes of the CRT were reported, but only among those who participated in project activities. The extent of benefits experienced was influenced by factors relating to the physical and social characteristics of each neighbourhood. The highest levels of change occurred in the presence of: (1) social cohesion, not only pre-existing but also as facilitated byWell Londonactivities; (2) personal and collective agency; (3) involvement and support of external organisations. Where the physical and social environment remained unchanged, there was less participation and fewer benefits.

Conclusions

These findings show interaction between participation, well-being and agency, social interactions and cohesion and that this modulated any benefits described. Pathways to change were thus complex and variable, but personal well-being and local social cohesion emerged as important mediators of change.
Impact of mothers’ employment on infant feeding and care: a qualitative study of the experiences of mothers employed through the Mahatma Gandhi National Rural Employment Guarantee Act
Authors: Nair Manisha , Ariana Proochista , Webster Premila
Published: April 2014

Objective

To explore the experiences of mothers employed through the Mahatma Gandhi National Rural Employment Guarantee Act (MGNREGA) using focus group discussions (FGDs) to understand the impact of mothers’ employment on infant feeding and care. The effects of mothers’ employment on nutritional status of children could be variable. It could lead to increased household income, but could also compromise child care and feeding.

Setting

The study was undertaken in the Dungarpur district of Rajasthan, India.

Participants

Mothers of infants <12 months of age. Ten FGDs, two in each of the five administrative blocks of the study district were conducted. The groups were composed of a minimum of 5 and maximum of 8 participants, giving a total of 62 mothers. Thematic analysis was conducted to assess patterns and generate emergent themes.

Results

Four major themes were identified—‘mothers' employment compromises infant feeding and care’, ‘caregivers’ inability to substitute mothers’ care’, ‘compromises related to childcare and feeding outweigh benefits from MGNREGA’ and ‘employment as disempowering’. Mothers felt that the comprises to infant care and feeding due to long hours of work, lack of alternative adequate care arrangements, low wages and delayed payments outweighed the benefits from the scheme.

Conclusions

This study provides an account of the trade-off between mothers’ employment and child care. It provides an understanding of the household power relationships, societal and cultural factors that modulate the effects of mothers’ employment. From the perspective of mothers, it helps to understand the benefits and problems related to providing employment to women with infants in the MGNREGA scheme and make a case to pursue policy changes to improve their working conditions.
Long-term psychological consequences of symptomatic pulmonary embolism: a qualitative study
Authors: Noble Simon , Lewis Rhian , Whithers Jodie , Lewis Sarah , Bennett Paul
Published: April 2014

Objective

To explore the psychological consequences of experiencing symptomatic pulmonary embolism (PE).

Design

Qualitative interview-based study using interpretative phenomenological analysis.

Setting

Outpatients who attended an anticoagulation clinic in a district general hospital.

Participants

Patients attending an anticoagulation clinic following hospital admission for symptomatic PE were approached to participate. A total of 9 (4 women, 5 men) of 11 patients approached agreed to be interviewed. Participants were aged between 26 and 72 years and had previously experienced a PE between 9 and 60 months (median=26 months, mean=24 months).

Intervention

Audiotaped semistructured qualitative interviews were undertaken to explore participants experiences of having a PE and how it had affected their lives since. Data were transcribed and analysed using interpretative phenomenological analysis to identify emergent themes.

Results

Three major themes with associated subthemes were identified. Participants described having a PE as a life-changing experience comprising initial shock, followed by feeling of loss of self, life-changing decisions and behaviour modification. Features of post-traumatic stress disorder (PTSD) were described with flashbacks, hypervigilance and intrusive thoughts being most prevalent. Participants identified several areas of support needed for such patients including easier access to support through information giving and emotional support.

Conclusions

Long-term consequences of venous thromboembolism go beyond the physical alone. Patients describe experiencing symptomatic PE to be a life-changing distressing event leading to behaviour modification and in some PTSD. It is likely that earlier psychological intervention may reduce such long-term sequelae.
Faecal calprotectin for differentiating between irritable bowel syndrome and inflammatory bowel disease: a useful screen in daily gastroenterology practice
Authors: Banerjee Ashwini , Srinivas M , Eyre Richard , Ellis Robert , Waugh Norman , Bardhan K D , Basumani P
Published: April 2014

Objective

To determine the best faecal calprotectin (FCP) cut-off level for differentiating between irritable bowel syndrome (IBS) and organic disease, particularly inflammatory bowel disease (IBD), in patients presenting with chronic diarrhoea.

Design

Retrospective analysis of patients who had colonoscopy, histology and FCP completed within 2 months.

Setting

District general hospital.

Patients

Consecutive new patients with chronic diarrhoea lasting longer than 4 weeks.

Interventions

Patients were seen by a single experienced gastroenterologist and listed for colonoscopy with histology. Laboratory investigations included a single faecal specimen for calprotectin assay (lower limit of detection: 8 µg/g), the results used for information only.

Main outcome measures

Six FCP cut-off levels (range 8–150 µg/g) were compared against the ‘gold standard’ of histology: inflammation ‘present’ or ‘absent’.

Results

Of 119 patients studied, 98 had normal colonoscopy and histology. The sensitivity of FCP to detect IBD at cut-off levels 8, 25 and 50 µg/g was 100% (with corresponding specificity 51%, 51%, 60%). In contrast, the lowest FCP cut-off, 8 µg/g, had 100% sensitivity to detect colonic inflammation, irrespective of cause (with negative predictive value (NPV) 100%). Importantly, 50/119 patients (42%) with FCP <8 µg/g had normal colonoscopy and histology.

Conclusions

Our results suggest that using FCP to screen patients newly referred for chronic diarrhoea could exclude all without IBD and, at a lower cut-off, all without colonic inflammation, thus avoiding the need for colonoscopy. Such a major reduction has implications for resource allocation.
Artificial insemination in dogs and cats 2. Artificial insemination in dogs
Authors: England Gary C. W. , Russo Marco , Freeman Sarah L.
Published: April 2014

An article in the February issue of In Practice discussed the benefits of artificial insemination in dogs and explained how to collect and preserve canine semen (In Practice, February 2014, vol 36, pp 77‐84). This second article discusses the practicalities of performing artificial insemination in dogs, giving advice on keeping the risk of adverse effects to a minimum.
High-sensitivity troponin as an outcome predictor in acute medical admissions
Authors: Courtney Danielle , Conway Richard , Kavanagh John , O'Riordan Deirdre , Silke Bernard
Published: April 2014

Background

Troponin estimation is increasingly performed on emergency medical admissions. We report on a high-sensitivity troponin (hscTn) assay, introduced in January 2011, and its relevance to in-hospital mortality in such patients.

Aim

To evaluate the impact of hscTn results on in-hospital mortality and the value of incorporating troponin into a predictive score of in-hospital mortality.

Methods

All patients admitted as general medical emergencies between January 2011 and October 2012 were studied. Patients admitted under other admitting services including cardiology were excluded. We examined outcomes using generalised estimating equations, an extension of generalised linear models that permitted adjustment for correlated observations (readmissions). Margins statistics used adjusted predictions to test for interactions of key predictors while controlling for other variables using computations of the average marginal effect.

Results

A total of 11 132 admission episodes were recorded. The in-hospital mortality for patients with predefined cut-offs was 1.9% when no troponin assay was requested, 5.1% when the troponin result was below the 25 ng/L ‘normal’ cut-off, 9.7% for a troponin result ≥25 and <50 ng/L, 14.5% for a troponin result ≥50 and <100 ng/L, 34.4% for a troponin result ≥100 and <1000 ng/L, and 58.3% for a troponin result >1000 ng/L. The OR for an in-hospital death for troponin-positive patients was 2.02 (95% CI 1.84 to 2.21); when adjusted for other mortality predictors including illness severity, the OR remained significant at 2.83 (95% CI 2.20 to 3.64). The incorporation of troponin into a multivariate logistic predictive algorithm resulted in an area under the receiver operating characteristic curve to predict an in-hospital death of 0.87 (95% CI 0.85 to 0.88).

Conclusions

An increase in troponin carries prognostic information in acutely ill medical patients; the extent of the risk conferred justifies incorporation of this information into predictive algorithms for hospital mortality.
Occurrence and molecular typing of Giardia isolates in pet rabbits, chinchillas, guinea pigs and ferrets collected in Europe during 2006–2012
Authors: Pantchev N. , Broglia A. , Paoletti B. , Vrhovec M. Globokar , Bertram A. , Nöckler K. , Cacciò S. M.
Published: April 2014

A total of 1180 faecal samples (528 from rabbits, 531 from chinchillas and 121 from guinea pigs) collected during 2006–2012 by veterinarians in Germany and in other European countries were submitted to a diagnostic laboratory for Giardia testing by means of coproantigen ELISA. Of these samples, 40 rabbits (7.6 per cent), 326 chinchillas (61.4 per cent) and five guinea pigs (4.1 per cent) were found to be positive. To gain insights into the genetic identity of Giardia in small mammals, ELISA‐positive samples from 23 chinchillas, five ferrets, a rabbit, and a Desmarest's hutia were investigated by PCR and sequencing of fragments of the small subunit ribosomal DNA (ssu), the triose phosphate isomerase (tpi) and the β‐giardin (bg) genes. At the ssu locus, assemblage B was identified in 28 of 30 isolates, whereas assemblage A and D were each detected in one sample. The majority of isolates from chinchillas and those from ferrets had Giardia duodenalis sequences identical to sub‐assemblages AI or BIV, based on either a single locus (tpi or bg) or multiple loci (tpi and bg). As sub‐assemblages AI or BIV are associated with human infection, these results indicate that small mammals can act as reservoirs of cysts potentially infectious to humans.
Microinjection of l-glutamate into the nucleus ambiguus partially inhibits gastric motility through the NMDA receptor – nitric oxide pathway
Authors: Sun Hong-Zhao , Zhao Shu-Zhen , Ai Hong-Bin
Published: April 2014

We have previously reported that both l-glutamate (l-Glu) and nitric oxide (NO) modulate gastric motility in the nucleus ambiguus (NA). The aim of this study is to explore the potential correlation between the l-Glu and NO. A latex balloon connected to a pressure transducer was inserted into the pylorus through the fundus of anesthetized male Wistar rats to continuously record changes in gastric smooth muscle contractile curves. Pretreatment with the NO-synthase inhibitor N-nitro-l-arginine methylester (l-NAME) did not completely abolish the inhibitory effect of l-Glu on gastric motility, but intravenous injection of the ganglionic blocker hexamethonium bromide (Hb) did. By using a specific N-methyl-d-aspartic acid (NMDA) receptor antagonist, we blocked the inhibitory effect of the NO-donor sodium nitroprusside (SNP) on gastric motility. These results suggest that microinjections of l-Glu into the NA inhibits gastric motility by activating the cholinergic preganglionic neurons, partially through the NMDA receptor – NO pathway.
Developmental determinants of cardiac sensitivity to hypoxia
Authors: Ostadal Bohuslav , Ostadalova Ivana , Kolar Frantisek , Sedmera David
Published: April 2014

Cardiac sensitivity to oxygen deprivation changes significantly during ontogenetic development. However, the mechanisms for the higher tolerance of the immature heart, possibilities of protection, and the potential impact of perinatal hypoxia on cardiac tolerance to oxygen deprivation in adults have not yet been satisfactorily clarified. The hypoxic tolerance of an isolated rat heart showed a triphasic pattern: significant decrease from postnatal day 1 to 7, followed by increase to the weaning period, and final decline to adulthood. We have observed significant ontogenetic changes in mitochondrial oxidative phosphorylation and mitochondrial membrane potential, as well as in the role of the mitochondrial permeability transition pores in myocardial injury. These results support the hypothesis that cardiac mitochondria are deeply involved in the regulation of cardiac tolerance to oxygen deprivation during ontogenetic development. Ischemic preconditioning failed to increase tolerance to oxygen deprivation in the highly tolerant hearts of newborn rats. Chronic hypoxic exposure during early development may cause in-utero or neonatal programming of several genes that can change the susceptibility of the adult heart to ischemia–reperfusion injury; this effect is sex dependent. These results would have important clinical implications, since cardiac sensitivity in adult patients may be significantly affected by perinatal hypoxia in a sex-dependent manner.
Analytical modelling of a deep tunnel in a viscoplastic rock mass accounting for a simplified life cycle and extension to a particular case of porous media
Authors: Deleruyelle F. , Bui T. A. , Wong H. , Dufour N.
Published: April 2014

An analytical approach to the viscoplastic behaviour of a rock mass around a deep tunnel in different stages of a simplified life cycle is presented. The viscoplasticity is modelled by means of a simple (linear) Norton–Hoff's law. First, the solution for a dry rock mass is presented, then an extension to a particular case of a porous saturated rock mass with a Poisson's ratio of 0.5 is examined. Some numerical examples are carried out to show the consistency and relevance of the solutions. Parametric studies illustrate the influence of key parameters such as rock mass viscosity and time of lining emplacement. This analytical approach constitutes a useful reference to test more complex numerical simulation and makes it possible to obtain practical estimations of the poromechanical behaviour of underground structures.
PACAP-induced ERK activation in HEK cells expressing PAC1 receptors involves both receptor internalization and PKC signaling
Authors: May Victor , Buttolph Thomas R. , Girard Beatrice M. , Clason Todd A. , Parsons Rodney L.
Published: April 2014

The pituitary adenylate cyclase-activating polypeptide (PACAP)-selective PAC1 receptor ( Adcyap1r1) is a G protein-coupled receptor (GPCR) that activates adenylyl cyclase and PLC. Similar to many other GPCRs, our previous studies showed that the PAC1 receptor is internalized after ligand binding to form signaling endosomes, which recruit additional second messenger pathways. Using a human embryonic kidney (HEK 293) PAC1Hop1-EGFP receptor cell line, we have examined how different PAC1 receptor signaling mechanisms contribute to MEK/ERK activation. Unlike PAC1 receptor-stimulated adenylyl cyclase/cAMP production in the plasma membrane, PACAP-mediated ERK phosphorylation was partly dependent on receptor internalization, as determined by treatment with pharmacological inhibitors of endocytosis or temperature reduction, which also suppressed receptor internalization. Stimulation of cAMP generation by forskolin or exposure to the cell-permeable cAMP analogs 8-bromo-cAMP and dibutyryl cAMP had minimal effects on ERK phosphorylation in this system. The ability of reduced temperature (24°C) to consistently suppress ERK activation to a greater extent than the endocytosis inhibitors Pitstop 2 and dynasore indicated that other mechanisms, in addition to PAC1 internalization/endosome activation, were involved. Inhibition of PAC1 receptor-stimulated PLC/diacylglycerol/PKC signaling by bisindoylmaleimide I also attenuated ERK phosphorylation, and direct PKC activation with phorbol ester increased ERK phosphorylation in a temperature-dependent manner. Inhibition of PAC1 receptor endocytosis and PKC activation completely blocked PACAP-stimulated ERK activation. PACAP augmented phosphorylated ERK staining uniformly over the cytoplasm and nucleus, and PKC signaling facilitated nuclear phosphorylated ERK translocation. In sum, our results show that PACAP/PAC1 receptor endocytosis and PLC/diacylglycerol/PKC activation represent two complementary mechanisms contributing to PACAP-induced ERK activation.
Identification and signature profiles for pro-resolving and inflammatory lipid mediators in human tissue
Authors: Colas Romain A. , Shinohara Masakazu , Dalli Jesmond , Chiang Nan , Serhan Charles N.
Published: April 2014

Resolution of acute inflammation is an active process locally controlled by a novel genus of specialized pro-resolving mediators (SPM) that orchestrate key resolution responses. Hence, it is of general interest to identify individual bioactive mediators and profile their biosynthetic pathways with related isomers as well as their relation(s) to classic eicosanoids in mammalian tissues. Lipid mediator (LM)-SPM levels and signature profiles of their biosynthetic pathways were investigated using liquid chromatography-tandem mass spectrometry (LC-MS-MS)-based LM metabololipidomics. LM and SPM were identified using ≥6 diagnostic ions and chromatographic behavior matching with both authentic and synthetic materials. This approach was validated using the composite reference plasma (SRM1950) of 100 healthy individuals. Using targeted LM metabololipidomics, we profiled LM and SPM pathways in human peripheral blood (plasma and serum) and lymphoid organs. In these, we identified endogenous SPM metabolomes, namely, the potent lipoxins (LX), resolvins (Rv), protectins (PD), and maresins (MaR). These included RvD1, RvD2, RvD3, MaR1, and NPD1/PD1, which were identified in amounts within their bioactive ranges. In plasma and serum, principal component analysis (PCA) identified signature profiles of eicosanoids and SPM clusters. Plasma-SPM increased with omega-3 and acetylsalicylic acid intake that correlated with increased phagocytosis of Escherichia coli in whole blood. These findings demonstrate an approach for identification of SPM pathways (e.g., resolvins, protectins, and maresins) in human blood and lymphoid tissues that were in amounts commensurate with their pro-resolving, organ protective, and tissue regeneration functions. LM metabololipidomics coupled with calibration tissues and physiological changes documented herein provide a tool for functional phenotypic profiling.
Lingual lipase activity in the orosensory detection of fat by humans
Authors: Kulkarni Bhushan V. , Mattes Richard D.
Published: April 2014

Lingual lipase generates nonesterified fatty acids (NEFA) from dietary fats during oral processing by lipolysis. Lingual lipase in rodents has strong lipolytic activity and plays a critical role in oral detection of fats. The functional activity of lingual lipase during oral processing of high-fat foods in humans remains poorly characterized. Five commonly consumed high-fat foods varying in physical states and fatty acid composition (almond, almond butter, olive oil, walnut, and coconut) were masticated by 15 healthy human subjects at the rate of one chew per second with and without lipase inhibitor orlistat. Salivary NEFA concentrations were measured. To determine the role of lingual lipase in oral fat detection, sensory ratings were obtained from the same 15 human subjects for almond butter with and without orlistat. Lingual lipase was active during oral processing of almond and coconut. No activity of lingual lipase was detected during processing of almond butter. There was only weak evidence lingual lipase is a determinant of oral fat detection. Lingual lipase may only contribute to NEFA generation and oral fat detection of fatty foods that require stronger oral processing effort.
HIV-1-Tat excites cardiac parasympathetic neurons of nucleus ambiguus and triggers prolonged bradycardia in conscious rats
Authors: Brailoiu Eugen , Deliu Elena , Sporici Romeo A. , Benamar Khalid , Brailoiu G. Cristina
Published: April 2014

The mechanisms of autonomic imbalance and subsequent cardiovascular manifestations in HIV-1-infected patients are poorly understood. We report here that HIV-1 transactivator of transcription (Tat, fragment 1–86) produced a concentration-dependent increase in cytosolic Ca2+in cardiac-projecting parasympathetic neurons of nucleus ambiguus retrogradely labeled with rhodamine. Using store-specific pharmacological agents, we identified several mechanisms of the Tat-induced Ca2+elevation: 1) lysosomal Ca2+mobilization, 2) Ca2+release via inositol 1,4,5-trisphosphate-sensitive endoplasmic reticulum pools, and 3) Ca2+influx via transient receptor potential vanilloid type 2 (TRPV2) channels. Activation of TRPV2, nonselective cation channels, induced a robust and prolonged neuronal membrane depolarization, thus triggering an additional P/Q-mediated Ca2+entry. In vivo microinjection studies indicate a dose-dependent, prolonged bradycardic effect of Tat administration into the nucleus ambiguus of conscious rats, in which neuronal TRPV2played a major role. Our results support previous studies, indicating that Tat promotes bradycardia and, consequently, may be involved in the QT interval prolongation reported in HIV-infected patients. In the context of an overall HIV-dependent autonomic dysfunction, these Tat-mediated mechanisms may account for the higher prevalence of sudden cardiac death in HIV-1-infected patients compared with general population with similar risk factors. Our results may be particularly relevant in view of the recent findings that significant Tat levels can still be identified in the cerebrospinal fluid of HIV-infected patients with viral load suppression due to efficient antiretroviral therapy.
Interleukin-6 contributes to early fasting-induced free fatty acid mobilization in mice
Authors: Wueest Stephan , Item Flurin , Boyle Christina N. , Jirkof Paulin , Cesarovic Nikola , Ellingsgaard Helga , Böni-Schnetzler Marianne , Timper Katharina , Arras Margarete , Donath Marc Y. , Lutz Thomas A. , Schoenle Eugen J. , Konrad Daniel
Published: April 2014

Contracting muscle releases interleukin-6 (IL-6) enabling the metabolic switch from carbohydrate to fat utilization. Similarly, metabolism is switched during transition from fed to fasting state. Herein, we examined a putative role for IL-6 in the metabolic adaptation to normal fasting. In lean C57BL/6J mice, 6 h of food withdrawal increased gene transcription levels of IL-6 in skeletal muscle but not in white adipose tissue. Concomitantly, circulating IL-6 and free fatty acid (FFA) levels were significantly increased, whereas respiratory quotient (RQ) was reduced in 6-h fasted mice. In white adipose tissue, phosphorylation of hormone-sensitive lipase (HSL) was increased on fasting, indicating increased lipolysis. Intriguingly, fasting-induced increase in circulating IL-6 levels and parallel rise in FFA concentration were absent in obese and glucose-intolerant mice. A causative role for IL-6 in the physiological adaptation to fasting was further supported by the fact that fasting-induced increase in circulating FFA levels was significantly blunted in lean IL-6 knockout (KO) and lean C57BL/6J mice treated with neutralizing IL-6 antibody. Consistently, phosphorylation of HSL was significantly reduced in adipose tissue of IL-6-depleted mice. Hence, our findings suggest a novel role for IL-6 in energy supply during early fasting.
Deterioration of kidney function by the (pro)renin receptor blocker handle region peptide in aliskiren-treated diabetic transgenic (mRen2)27 rats
Authors: te Riet Luuk , van den Heuvel Mieke , Peutz-Kootstra Carine J. , van Esch Joep H. M. , van Veghel Richard , Garrelds Ingrid M. , Musterd-Bhaggoe Usha , Bouhuizen Angelique M. , Leijten Frank P. J. , Danser A. H. Jan , Batenburg Wendy W.
Published: April 2014

Dual renin-angiotensin system (RAS) blockade in diabetic nephropathy is no longer feasible because of the profit/side effect imbalance. (Pro)renin receptor [(P)RR] blockade with handle region peptide (HRP) has been reported to exert beneficial effects in various diabetic models in a RAS-independent manner. To what degree (P)RR blockade adds benefits on top of RAS blockade is still unknown. In the present study, we treated diabetic TGR(mREN2)27 rats, a well-established nephropathy model with high prorenin levels [allowing continuous (P)RR stimulation in vivo], with HRP on top of renin inhibition with aliskiren. Aliskiren alone lowered blood pressure and exerted renoprotective effects, as evidenced by reduced glomerulosclerosis, diuresis, proteinuria, albuminuria, and urinary aldosterone levels as well as diminished renal (P)RR and ANG II type 1 receptor expression. It also suppressed plasma and tissue RAS activity and suppressed cardiac atrial natriuretic peptide and brain natriuretic peptide expression. HRP, when given on top of aliskiren, did not alter the effects of renin inhibition on blood pressure, RAS activity, or aldosterone. However, it counteracted the beneficial effects of aliskiren in the kidney, induced hyperkalemia, and increased plasma plasminogen activator-inhibitor 1, renal cyclooxygenase-2, and cardiac collagen content. All these effects have been linked to (P)RR stimulation, suggesting that HRP might, in fact, act as a partial agonist. Therefore, the use of HRP on top of RAS blockade in diabetic nephropathy is not advisable.
Akt and RhoA activation in response to high glucose require caveolin-1 phosphorylation in mesangial cells
Authors: Wu Su-Zhen , Peng Fang-Fang , Li Jia-Lin , Ye Feng , Lei Shao-Qing , Zhang Bai-Fang
Published: April 2014

Glomerular matrix accumulation is a hallmark of diabetic renal disease. Serine/threonine kinase PKC-β1 mediates glucose-induced Akt S473 phosphorylation, RhoA activation, and transforming growth factor (TGF)-β1 upregulation and finally leads to matrix upregulation in mesangial cells (MCs). It has been reported that glucose-induced PKC-β1 activation is dependent on caveolin-1 and the presence of intact caveolae in MCs; however, whether activated PKC-β1 regulates caveolin-1 expression and phosphorylation are unknown. Here, we showed that, although the caveolin-1 protein level had no significant change, the PKC-β-specific inhibitor LY-333531 blocked caveolin-1 Y14 phosphorylation in high glucose (HG)-treated MCs and in the renal cortex of diabetic rats. The Src-specific inhibitor SU-6656 prevented the HG-induced association between PKC-β1 and caveolin-1 and PKC-β1 membrane translocation, whereas PKC-β1 small interfering RNA failed to block Src activation, indicating that Src kinase is upstream of PKC-β1 activation. Although LY-333531 blocked PKC-β1 membrane translocation, it had no effect on the PKC-β1/caveolin-1 association, suggesting that PKC-β1 activation requires the interaction of caveolin-1 and PKC-β1. PKC-β1-mediated Akt S473 phosphorylation, RhoA activation, and fibronectin upregulation in response to HG were prevented by SU-6656 and nonphosphorylatable mutant caveolin-1 Y14A. In conclusion, Src activation by HG mediates the PKC-β1/caveolin-1 association and PKC-β1 activation, which assists in caveolin-1 Y14 phosphorylation by Src kinase. The downstream effects, including Akt S473 phosphorylation, RhoA activation, and fibronectin upregulation, require caveolin-1 Y14 phosphorylation. Caveolin-1 is thus an important mediator of the profibrogenic process in diabetic renal disease.
Development of neural responsivity to vocal sounds in higher level auditory cortex of songbirds
Authors: Miller-Sims Vanessa C. , Bottjer Sarah W.
Published: April 2014

Like humans, songbirds learn vocal sounds from “tutors” during a sensitive period of development. Vocal learning in songbirds therefore provides a powerful model system for investigating neural mechanisms by which memories of learned vocal sounds are stored. This study examined whether NCM (caudo-medial nidopallium), a region of higher level auditory cortex in songbirds, serves as a locus where a neural memory of tutor sounds is acquired during early stages of vocal learning. NCM neurons respond well to complex auditory stimuli, and evoked activity in many NCM neurons habituates such that the response to a stimulus that is heard repeatedly decreases to approximately one-half its original level (stimulus-specific adaptation). The rate of neural habituation serves as an index of familiarity, being low for familiar sounds, but high for novel sounds. We found that response strength across different song stimuli was higher in NCM neurons of adult zebra finches than in juveniles, and that only adult NCM responded selectively to tutor song. The rate of habituation across both tutor song and novel conspecific songs was lower in adult than in juvenile NCM, indicating higher familiarity and a more persistent response to song stimuli in adults. In juvenile birds that have memorized tutor vocal sounds, neural habituation was higher for tutor song than for a familiar conspecific song. This unexpected result suggests that the response to tutor song in NCM at this age may be subject to top-down influences that maintain the tutor song as a salient stimulus, despite its high level of familiarity.
Metallothionein Induction in the Coelomic Fluid of the EarthwormLumbricus terrestrisfollowing Heavy Metal Exposure: A Short Report
Authors: Calisi A. , Lionetto M. G. , De Lorenzis E. , Leomanni A. , Schettino T.
Published: April 2014

Earthworms are useful bioindicator organisms for soil biomonitoring. Recently the use of pollution biomarkers in earthworms has been increasingly investigated for soil monitoring and assessment. Earthworm coelomic fluid is particularly interesting from a toxicological perspective, because it is responsible for pollutant disposition and tissue distribution to the whole organism. The aim of the present work was to study the effect of heavy metal exposure on metallothionein (Mt) induction in the coelomic fluid ofLumbricus terrestrisin view of future use as sensitive biomarker suitable for application to metal polluted soil monitoring and assessment.L. terrestriscoelomic fluid showed a detectable Mt concentration of about4.0±0.6 μg/mL (mean ± SEM,n=10) in basal physiological condition. When the animals were exposed to CuSO4or CdCl2or to a mixture of the two metals in OECD soils for 72 h, the Mt specific concentration significantly (P<0.001) increased. The Mt response in the coelomic fluid perfectly reflected the commonly used Mt response in the whole organism when the two responses were compared on the same specimens. These findings indicate the suitability of Mt determination inL. terrestriscoelomic fluid as a sensitive biomarker for application to metal polluted soil monitoring and assessment.
Resistance Training and Testosterone Levels in Male Patients with Chronic Kidney Disease Undergoing Dialysis
Authors: Molsted Stig , Andersen Jesper L. , Eidemak Inge , Harrison Adrian P. , Jørgensen Niels
Published: April 2014

Background.We investigated serum testosterone and insulin-like growth factor 1 (IGF-1) levels’ associations with muscle fibre size and resistance training in male dialysis patients.Methods.Male patients were included in a 16-week control period followed by 16 weeks of resistance training thrice weekly. Blood samples were obtained to analyse testosterone, luteinizing hormone (LH), IGF-1, and IGF-binding protein 3. Muscle fibres’ size was analysed in biopsies fromm. vastus lateralis.Results.The patients’ testosterone levels were within the normal range at baseline (n=20) (19.5 (8.2–52.1) nmol/L versus 17.6 (16.1–18.0), resp.) whereas LH levels were higher (13.0 (5.5–82.8) U/L versus 4.3 (3.3–4.6),P<0.001, resp.). IGF-1 and IGF-binding protein 3 levels were higher in the patients compared with reference values (203 (59–590) ng/mL versus 151 (128–276),P=0.014, and 5045 (3370–9370) ng/mL versus 3244 (3020–3983),P<0.001, resp.). All hormone levels and muscle fibre size (n=12) remained stable throughout the study. Age-adjusted IGF-1 was associated with type 1 and 2 fibre sizes (P<0.05).Conclusion.Patients’ total testosterone values were normal due to markedly increased LH values, which suggest a compensated primary insufficiency of the testosterone producing Leydig cell. Even though testosterone values were normal, resistance training was not associated with muscle hypertrophy. This trial is registered withISRCTN72099857.
Phylogenetic Analysis of Entomoparasitic Nematodes, Potential Control Agents of Flea Populations in Natural Foci of Plague
Authors: Koshel E. I. , Aleshin V. V. , Eroshenko G. A. , Kutyrev V. V.
Published: April 2014

Entomoparasitic nematodes are natural control agents for many insect pests, including fleas that transmitYersinia pestis, a causative agent of plague, in the natural foci of this extremely dangerous zoonosis. We examined the flea samples from the Volga-Ural natural focus of plague for their infestation with nematodes. Among the six flea species feeding on different rodent hosts (Citellus pygmaeus,Microtus socialis, andAllactaga major), the rate of infestation varied from 0 to 21%. The propagation rate of parasitic nematodes in the haemocoel of infected fleas was very high; in some cases, we observed up to 1,000 juveniles per flea specimen. Our study of morphology, life cycle, and rDNA sequences of these parasites revealed that they belong to three distinct species differing in the host specificity. On SSU and LSU rRNA phylogenies, these species representing three genera (Rubzovinema,Psyllotylenchus, andSpilotylenchus), constitute a monophyletic group close to Allantonema and Parasitylenchus, the type genera of the families Allantonematidae and Parasitylenchidae (Nematoda: Tylenchida). We discuss the SSU-ITS1-5.8S-LSU rDNA phylogeny of the Tylenchida with a special emphasis on the suborder Hexatylina.
Relation of Asymmetric Dimethylarginine Levels to Macrovascular Disease and Inflammation Markers in Type 2 Diabetic Patients
Authors: Celik Mustafa , Cerrah Serkan , Arabul Mahmut , Akalin Aysen
Published: April 2014

Aim. We aimed to determine the relation of asymmetric dimethyl arginine (ADMA) levels to atherosclerotic vascular disease and inflammation markers in type 2 diabetes.Methods. We recruited 50 type 2 diabetic patients with atherosclerosis, 50 type 2 diabetic patients without atherosclerosis, and 31 healthy control patients into our study. We obtained fasting serum and plasma samples and measured HbA1c, fasting blood glucose, C-peptide, creatinine, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, hsCRP, fibrinogen, erythrocyte sedimentation rate, total homocysteine, and ADMA levels. In addition, all of the patients were evaluated for carotid artery intima media thickness by ultrasound. We evaluated ADMA levels in healthy controls, diabetic patients with macrovascular complications, and diabetic patients without macrovascular complications and evaluated the relationship between ADMA levels and total homocysteine, inflammation markers, and macrovascular disease.Results. Mean ADMA values in non-MVD and control groups were significantly lower than in MVD group (0.39±0.16,0.32±0.13,0.52±0.23,P<0.05, resp.). These three variables (carotid intima-media thickness, inflammatory markers, and ADMA levels) were significantly higher in diabetes group than control (P<0.05).Conclusion. There is a relationship between ADMA and macrovascular disease in type 2 diabetes, but further studies are needed to understand whether increased ADMA levels are a cause of macrovascular disease or a result of macrovascular disease.
Theory Analysis of Left-Handed Grünwald-Letnikov Formula with0<α<1to Detect and Locate Singularities
Authors: Hu Shaoxiang , Liang Ping
Published: April 2014

We study fractional-order derivatives of left-handed Grünwald-Letnikov formula with0<α<1to detect and locate singularities in theory. The widely used four types of ideal singularities are analyzed by deducing their fractional derivative formula. The local extrema of fractional derivatives are used to locate the singularities. Theory analysis indicates that fractional-order derivatives of left-handed Grünwald-Letnikov formula with0<α<1can detect and locate four types of ideal singularities correctly, which shows better performance than classical 1-order derivatives in theory.
Correction of Channel Imbalance for MIMO SAR Using Stepped-Frequency Chirps
Authors: Luo Xiulian , Deng Yunkai , Wang Robert , Guo Lei , Wang Mingjiang
Published: April 2014

To simultaneously achieve two-dimensional high resolution and wide swath in synthetic aperture radar (SAR), azimuth MIMO structure combined with stepped-frequency chirp signals was developed via splitting the antenna intoNsubapertures. During transmitting each subaperture transmits a chirp pulse at a different carrier frequency, while during receiving every subaperture receives theNscattered pulses at the same time. Separating theNscattered pulses received by each subaperture and downlinking them to the ground yieldN2different signal paths. Due to the dedicated network in the SAR system, the channel imbalance is inevitable. To correct the channel imbalance, this paper presents an external calibration method, where the channel characteristics are estimated from the peak value of a strong point target for each channel. Simulation and real raw data experiments are performed to validate the proposed method.
Moisture Diffusivity and Shrinkage of Fruit and Cladode of Opuntia ficus-indica during Infrared Drying
Authors: Touil Amira , Chemkhi Saber , Zagrouba Fethi
Published: April 2014

Drying behaviour of prickly pear cladodes and fruits was studied with an Infrared dryer. The volume shrinkage for Opuntia ficus-indica products is calculated and a linear relation was established to describe the experimental variation of shrinkage of the product versus its moisture content. Effective diffusion coefficient of moisture transfer was determined using the Fick law at three drying temperatures (40, 50, and 60°C). Shrinkage was also included into the diffusion model for the determination of the effective diffusion coefficient. The obtained results of the effective moisture diffusivity, for the cladode and the fruit, were evaluated in the range of 1.77 × 10−10–5.07 × 10−10 m2/s and 2.53 × 10−10–7.6 × 10−10 m2/s, respectively. The values of the activation energies for cladode and fruit were estimated to be 45.39 and 47.79 kJ/mol, respectively. However, these values of moisture diffusivity were estimated independently of the evolution of moisture content during drying process. Therefore, a correlation (full quadratic equation) for moisture diffusivity as a function of moisture content and temperature was developed. The parameters are obtained by a multilinear regression method. This equation was found satisfactory to describe the diffusivity evolution function of moisture content and temperature with correlation coefficients of 91.5 and 95%.
Characterization of Imidazoline Receptors in Blood Vessels for the Development of Antihypertensive Agents
Authors: Chen Mei-Fen , Tsai Jo-Ting , Chen Li-Jen , Wu Tung-Pi , Yang Jia-Jang , Yin Li-Te , Yang Yu-lin , Chiang Tai-An , Lu Han-Lin , Wu Ming-Chang
Published: April 2014

It has been indicated that activation of peripheral imidazoline I2-receptor (I-2R) may reduce the blood pressure in spontaneously hypertensive rats (SHRs). Also, guanidinium derivatives show the ability to activate imidazoline receptors. Thus, it is of special interest to characterize the I-2R using guanidinium derivatives in blood vessels for development of antihypertensive agent(s). Six guanidinium derivatives including agmatine, amiloride, aminoguanidine, allantoin, canavanine, and metformin were applied in this study. Western blot analysis was used for detecting the expression of imidazoline receptor in tissues of Wistar rats. The isometric tension of aortic rings isolated from male rats was also estimated. The expression of imidazoline receptor on rat aorta was identified. However, guanidinium derivatives for detection of aortic relaxation were not observed except agmatine and amiloride which induced a marked relaxation in isolated aortic rings precontracted with phenylephrine or KCl. Both relaxations induced by agmatine and amiloride were attenuated by glibenclamide at concentration enough to block ATP-sensitive potassium (KATP) channels. Meanwhile, only agmatine-induced relaxation was abolished by BU224, a selective antagonist of imidazoline I2-receptors. Taken together, we suggest that agmatine can induce vascular relaxation through activation of peripheral imidazoline I2-receptor to openKATPchannels. Thus, agmatine-like compound has the potential to develop as a new therapeutic agent for hypertension in the future.
Oleoylethanolamide: A Novel Potential Pharmacological Alternative to Cannabinoid Antagonists for the Control of Appetite
Authors: Romano Adele , Coccurello Roberto , Giacovazzo Giacomo , Bedse Gaurav , Moles Anna , Gaetani Silvana
Published: April 2014

The initial pharmaceutical interest for the endocannabinoid system as a target for antiobesity therapies has been restricted by the severe adverse effects of the CB1 antagonist rimonabant. This study points at oleoylethanolamide (OEA), a monounsaturated analogue, and functional antagonist of anandamide, as a potential and safer antiobesity alternative to CB1 antagonism. Mice treated with equal doses (5 or 10 mg/kg, i.p.) of OEA or rimonabant were analyzed for the progressive expression of spontaneous behaviors (eating, grooming, rearing, locomotion, and resting) occurring during the development of satiety, according to the paradigm called behavioral satiety sequence (BSS). Both drugs reduced food (wet mash) intake to a similar extent. OEA treatment decreased eating activity within the first 30 min and caused a temporary increase of resting time that was not accompanied by any decline of horizontal, vertical and total motor activity. Besides decreasing eating activity, rimonabant caused a marked increase of the time spent grooming and decreased horizontal motor activity, alterations that might be indicative of aversive nonmotivational effects on feeding. These results support the idea that OEA suppresses appetite by stimulating satiety and that its profile of action might be predictive of safer effects in humans as a novel antiobesity treatment.
Privacy-Preserving Discovery of Topic-Based Events from Social Sensor Signals: An Experimental Study on Twitter
Authors: Nguyen Duc T. , Jung Jai E.
Published: April 2014

Social network services (e.g., Twitter and Facebook) can be regarded as social sensors which can capture a number of events in the society. Particularly, in terms of time and space, various smart devices have improved the accessibility to the social network services. In this paper, we present a social software platform to detect a number of meaningful events from information diffusion patterns on such social network services. The most important feature is to process the social sensor signal for understanding social events and to support users to share relevant information along the social links. The platform has been applied to fetch and cluster tweets from Twitter into relevant categories to reveal hot topics.
Analyzing Black Hole Super-Radiance Emission of Particles/Energy from a Black Hole as a Gedankenexperiment to Get Bounds on the Mass of a Graviton
Authors: Beckwith A.
Published: April 2014

Use of super-radiance in BH physics, sodE/dt<0specifies conditions for a mass of a graviton being less than or equal to 1065grams, allows for determing what role additional dimensions may play in removing the datum that massive gravitons lead to 3/4th the bending of light past the planet Mercury. The present document makes a given differentiation between super-radiance in the case of conventional BHs and Braneworld BH super-radiance, which may delineate whether Braneworlds contribute to an admissible massive graviton in terms of removing the usual problem of the 3/4th the bending of light past the planet Mercury which is normally associated with massive gravitons. This leads to a fork in the road between two alternatives with the possibility of needing a multiverse containment of BH structure or embracing what Hawkings wrote up recently, namely, a redo of the event horizon hypothesis as we know it.