bluuebunny/crossref_metadata_2025_split huggingface dataset:
Which Technique Is Better for Detection of Right‐to‐Left Shunt in Patients with Patent Foramen Ovale: Comparing Contrast Transthoracic Echocardiography with Contrast Transesophageal Echocardiography
Authors: Li Yue , Ya‐nan Zhai , Li‐qun Wei 
Published: February 2014

BackgroundAt present there is no consensus on which technique is more suitable for the detection of right‐to‐left shunt (RLS) in patients with patent foramen ovale (PFO). The aim of study was to compare the efficacy of contrast transthoracic echocardiography (cTTE) and contrast transesophageal echocardiography (cTEE) in the detection of RLS.MethodsA prospective study was undertaken in 29 patients with PFO. Both cTTE with harmonic imaging modality and cTEE with fundamental imaging modality were performed for all the patients. The severity of RLS were semiquantitatively assessed with a four‐level grade system by scaling the numbers of microbubbles (MBs) in the left atrium after complete opacification of the right atrium within the first 3 cardiac cycles. Level 1 represents no MBs, indicating no RLS. Level 2, ≤10 MBs, indicating mild RLS. Level 3, 11–30 MBs, indicating moderate RLS and Level 4, >30 MBs, indicating severe RLS.ResultsContrast TTE demonstrated significantly higher sensitivity for detection of RLS than cTEE (86% vs. 56%, P < 0.05). For cTTE, there were 4, 1, 5, and 19 cases determined at levels 1, 2, 3, and 4, respectively, whereas for the same group of patients 13, 2, 6, and 7 cases were identified by cTEE at levels 1, 2, 3, and 4, respectively. The severity of RLS detected by cTTE was significantly greater than that by cTEE (P < 0.01).ConclusionsContrast TTE is more efficacious in the detection of RLS than cTEE. The former can be used as an alternative to the latter in clinical practice.
Effectiveness of training senior dental students on oral health care for disabled patients
Authors: Mohebbi S. Z. , Chinipardaz Z. , Batebi A. 
Published: February 2014

AbstractIntroductionStudies in several countries have shown that dental students need an improved educational programme concerning management of disabled patients. We aimed to study the effect of providing a course entitled ‘Oral health care of disabled patients' on knowledge and attitudes of senior dental students at Tehran University.Materials and methodsA total number of 70 students (n = 70) were asked to fill in a questionnaire regarding their background, knowledge and attitudes, before and after the programme. The intervention group of 36 students (n = 36) received a four‐session course consisting of lectures, group discussion, screening and fluoride varnish provision for disabled patients. Statistical analysis was performed using the Mann–Whitney U‐test, the chi‐square test and linear regression modelling.ResultsAmongst all the participants, 36% had previously treated a disabled patient and 58% believed that merely specialists should treat disabled patients. Twenty‐seven percentage of participants believed that hospital is the only proper facility for treating disabled patients. A considerable improvement in both knowledge and attitudes of students was observed following the intervention (P < 0.05).ConclusionsOur findings indicate that a short‐term training programme on oral health care has an immense impact on students' adherence to treating disabled patients. These results provide evidence to support the necessity of enrichment of the dental curriculum regarding oral health care for disabled patients.
The molecular interplay between endocannabinoid and neurotrophin signals in the nervous system and beyond
Authors: Keimpema Erik , Hökfelt Tomas , Harkany Tibor , Doherty Patrick 
Published: February 2014

AbstractNeurotrophins are traditionally known for their roles in neuronal development, function and survival. More recent data has highlighted the importance of neurotrophin signalling in adult signalling contexts, including the regulation of synaptic transmission. In addition, neurotrophin levels are increased in inflammatory and neuropathic pain leading to sensitization to painful stimuli. Endocannabinoid (eCB) signalling was initially studied in the context of synaptic transmission and pain alleviation whilst recently gaining attention due to its involvement in the development of the nervous system. Similar to neurotrophins, eCB levels also rise during pain perception but result in diminished pain sensations. The overlap of cellular functions between neurotrophins and eCB signalling leads to the hypothesis that these signalling systems are positioned to regulate each other and narrow the multitude of actions that both systems can promote to the specific need of the cell. Therefore, in this review, we examine to what extent the involvement of these two signalling systems is co‐ordinated as opposed to being coincidental, and causal to neuronal circuit modifications in pain. Available data point to numerous direct molecular interactions between the neurotrophin and eCB signalling systems in developmental and adult contexts, including receptor‐level interplay, transcriptional control and synergistic regulation of downstream signalling cascades. Although experimental observations specifically in pain circuits are limited, the universality of downstream signalling systems from both neurotrophin and endocannabinoid receptors suggest an interdependent relationship between these two diverse signalling systems.
Neurobiology of pain, interoception and emotional response: lessons from nerve growth factor‐dependent neurons
Authors: Indo Yasuhiro 
Published: February 2014

AbstractAlthough nerve growth factor (NGF) is a well‐known neurotrophic factor, it also acts as a mediator of pain, itch and inflammation. Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive genetic disorder caused by loss‐of‐function mutations inNTRK1, the gene encoding a receptor tyrosine kinase for NGF, TrkA. Mutations inNTRK1cause the selective loss of NGF‐dependent neurons in otherwise intact systems. NGF‐dependent primary afferents are thinly myelinated Aδ or unmyelinated C‐fibers that are dependent on the NGF–TrkA system during development. In CIPA, the lack of pain and the presence of anhidrosis (inability to sweat) are due to the absence of both NGF‐dependent primary afferents and sympathetic postganglionic neurons, respectively. These peripheral neurons form an interface between the nervous system and the ‘body‐proper’ and play essential roles in the interoception and sympathetic regulation of various tissues or organs. Patients with CIPA also show mental retardation and characteristic behaviors and are probably neuron‐deficient within the brain. However, the functions of NGF‐dependent neurons in the brain are controversial, both in animal and in human studies. This review focuses on various brain regions that express TrkAmRNA, based on data from theAllen Human Brain Atlas, and discusses putative neuronal networks related to these brain regions in humans. A better understanding the distribution of NGF‐dependent neurons in the brain will provide a framework for further studies to investigate pain, interoception and emotional responses. Furthermore, strategies targeting the molecular mechanisms through which the NGF–TrkA system functions may provide hope for the development of novel analgesics.
Neurotrophins, endocannabinoids and thermo‐transient receptor potential: a threesome in pain signalling
Authors: Devesa Isabel , Ferrer‐Montiel Antonio 
Published: February 2014

AbstractBecause of the social and economic costs of chronic pain, there is a growing interest in unveiling the cellular and molecular mechanisms underlying it with the aim of developing more effective medications. Pain signalling is a multicomponent process that involves the peripheral and central nervous systems. At the periphery, nociceptor sensitisation by pro‐inflammatory mediators is a primary step in pain transduction. Although pain is multifactorial at cellular and molecular levels, it is widely accepted that neurotrophin (TrkA, p75NTR, Ret and GFRs), cannabinoid (CB1 and CB2), and thermo‐transient receptor potential (TRPs; TRPV1, TRPA1 and TRPM8) receptors play a pivotal role. They form a threesome for which endocannabinoids appear to be a first line of defence against pain, while neurotrophins and thermoTRPs are the major generators of painful signals. However, endocannabinoids may exhibit nociceptive activity while some neurotrophins may display anti‐nociception. Accordingly, a clear‐cut knowledge of the modulation and context‐dependent function of these signalling cascades, along with the molecular and dynamic details of their crosstalk, is critical for understanding and controlling pain transduction. Here, the recent progress in this fascinating topic, as well as the tantalizing questions that remain unanswered, will be discussed. Furthermore, we will underline the need for using a systems biology approach (referred to as systems pain) to uncover the dynamics and interplay of these intricate signalling cascades, taking into consideration the molecular complexity and cellular heterogeneity of nociceptor populations. Nonetheless, the available information confirms that pharmacological modulation of this signalling triad is a highly valuable therapeutic strategy for effectively treating pain syndromes.
Pro‐neurotrophins, sortilin, and nociception
Authors: Lewin Gary R. , Nykjaer Anders 
Published: February 2014

AbstractNerve growth factor (NGF) signaling is important in the development and functional maintenance of nociceptors, but it also plays a central role in initiating and sustaining heat and mechanical hyperalgesia following inflammation. NGF signaling in pain has traditionally been thought of as primarily engaging the classic high‐affinity receptor tyrosine kinase receptor TrkA to initiate sensitization events. However, the discovery that secreted proforms of nerve NGF have biological functions distinct from the processed mature factors raised the possibility that these proneurotrophins (proNTs) may have distinct function in painful conditions. ProNTs engage a novel receptor system that is distinct from that of mature neurotrophins, consisting of sortilin, a type I membrane protein belonging to the VPS10p family, and its co‐receptor, the classic low‐affinity neurotrophin receptor p75NTR. Here, we review how this new receptor system may itself function with or independently of the classic TrkA system in regulating inflammatory or neuropathic pain.
Heterogeneous presynaptic distribution of monoacylglycerol lipase, a multipotent regulator of nociceptive circuits in the mouse spinal cord
Authors: Horváth Eszter , Woodhams Stephen G. , Nyilas Rita , Henstridge Christopher M. , Kano Masanobu , Sakimura Kenji , Watanabe Masahiko , Katona István 
Published: February 2014

AbstractMonoacylglycerol lipase (MGL) is a multifunctional serine hydrolase, which terminates anti‐nociceptive endocannabinoid signaling and promotes pro‐nociceptive prostaglandin signaling. Accordingly, both acute nociception and its sensitization in chronic pain models are prevented by systemic or focal spinal inhibition of MGL activity. Despite its analgesic potential, the neurobiological substrates of beneficial MGL blockade have remained unexplored. Therefore, we examined the regional, cellular and subcellular distribution of MGL in spinal circuits involved in nociceptive processing. All immunohistochemical findings obtained with light, confocal or electron microscopy were validated in MGL‐knockout mice. Immunoperoxidase staining revealed a highly concentrated accumulation of MGL in the dorsal horn, especially in superficial layers. Further electron microscopic analysis uncovered that the majority of MGL‐immunolabeling is found in axon terminals forming either asymmetric glutamatergic or symmetric γ‐aminobutyric acid/glycinergic synapses in laminae I/IIo. In line with this presynaptic localization, analysis of double‐immunofluorescence staining by confocal microscopy showed that MGL colocalizes with neurochemical markers of peptidergic and non‐peptidergic nociceptive terminals, and also with markers of local excitatory or inhibitory interneurons. Interestingly, the ratio of MGL‐immunolabeling was highest in calcitonin gene‐related peptide‐positive peptidergic primary afferents, and the staining intensity of nociceptive terminals was significantly reduced in MGL‐knockout mice. These observations highlight the spinal nociceptor synapse as a potential anatomical site for the analgesic effects of MGL blockade. Moreover, the presence of MGL in additional terminal types raises the possibility that MGL may play distinct regulatory roles in synaptic endocannabinoid or prostaglandin signaling according to its different cellular locations in the dorsal horn pain circuitry.
No more pain upon Gq‐protein‐coupled receptor activation: role of endocannabinoids
Authors: Hu Sherry Shu‐Jung , Ho Yu‐Cheng , Chiou Lih‐Chu 
Published: February 2014

AbstractMarijuana has been used to relieve pain for centuries. The analgesic mechanism of its constituents, the cannabinoids, was only revealed after the discovery of cannabinoid receptors (CB1 and CB2) two decades ago. The subsequent identification of the endocannabinoids, anandamide and 2‐arachidonoylglycerol (2‐AG), and their biosynthetic and degradation enzymes discloses the therapeutic potential of compounds targeting the endocannabinoid system for pain control. Inhibitors of the anandamide and 2‐AG degradation enzymes, fatty acid amide hydrolase and monoacylglycerol lipase, respectively, may be superior to direct cannabinoid receptor ligands as endocannabinoids are synthesized on demand and rapidly degraded, focusing action at generating sites. Recently, a promising strategy for pain relief was revealed in the periaqueductal gray (PAG). It is initiated by Gq‐protein‐coupled receptor (GqPCR) activation of the phospholipase C–diacylglycerol lipase enzymatic cascade, generating 2‐AG that produces inhibition of GABAergic transmission (disinhibition) in the PAG, thereby leading to analgesia. Here, we introduce the antinociceptive properties of exogenous cannabinoids and endocannabinoids, involving their biosynthesis and degradation processes, particularly in the PAG. We also review recent studies disclosing the GqPCR–phospholipase C–diacylglycerol lipase–2‐AG retrograde disinhibition mechanism in the PAG, induced by activating several GqPCRs, including metabotropic glutamatergic (type 5 metabotropic glutamate receptor), muscarinic acetylcholine (M1/M3), and orexin 1 receptors. Disinhibition mediated by type 5 metabotropic glutamate receptor can be initiated by glutamate transporter inhibitors or indirectly by substance P, neurotensin, cholecystokinin and capsaicin. Finally, the putative role of 2‐AG generated after activating the above neurotransmitter receptors in stress‐induced analgesia is discussed.
Do Male Activity Level And Territory Quality Affect Female Association Time in The Brown Anole, Anolis sagrei?
Authors: Flanagan Sarah P. , Bevier Catherine R. 
Published: February 2014

AbstractFemale mate preference is an important component of sexual selection because some male traits, such as physiology and proficiency in acquiring resources, are indicators of male quality. In lizards, the importance of female choice remains unclear as results reported from previous experiments are contradictory. Here, we investigated the influence of male activity level, its associated physiology, and territory quality on female preference, estimated as association time, for male brown anoles, Anolis sagrei. Male A. sagrei were first rated for endurance then used in mismatched‐pair female association trials. Preference was scored as the time a female spent near a male relative to the amount of time she was in his half of the trial arena, and both male and female behaviors were recorded. Levels of blood glucose were measured in males before and after the endurance tests, and before and after the association trials. Levels of stored glycogen were measured in leg muscle and liver samples collected from males after an association trial. A path analysis indicates that final blood glucose levels affect male activity and that female preference is influenced by male activity. In a second experiment, females were given a choice between a male in a territory supplemented with plants and a size‐matched male in a bare territory. Male activity levels were recorded when both males interacted with the female. In those cases, females spent more time with the more active of the two males, regardless of territory quality. Combined, these results suggest that female A. sagrei exhibit preference for male activity regardless of territory quality.
Anticoagulants for secondary prevention after acute myocardial infarction: lessons from the past decade
Authors: Atar Dan , Bode Christoph , Stuerzenbecher André , Verheugt Freek W. A. 
Published: February 2014

AbstractThe impact of an acute coronary syndrome (ACS) event, such as an acute myocardial infarction (MI), is not limited to the acute management phase; patients face an elevated risk of residual atherothrombotic events that commonly requires chronic management for months or even years. Significant advances have been made in both the acute and chronic management of patients with acuteMIover the past decade, resulting in improved prognoses. One of the hallmarks of modern treatment strategies is more aggressive antiplatelet treatment regimens. However, the risks of furtherACSevents, stroke and premature death remain elevated in these patients, and addressing this residual risk is challenging owing to interpatient variability, differences in management strategies between centres and countries, incomplete understanding of the specific pathophysiology of post‐ACSthrombosis and limitations of current therapeutic approaches. The recent approval inEurope of the direct oral anticoagulant rivaroxaban for use in this setting in combination with clopidogrel and acetylsalicylic acid offers another strategy to consider in the management of these patients, and clinical strategies in this area continue to evolve. In this review, we chart the progress made over the past decade in reducing the burden of secondary thromboembolic events after acuteMIand discuss the current position of and future perspectives on the inclusion of oral anticoagulants into care pathways in this setting.
Predictions of climate change infer increased environmental harshness and altered connectivity in a cluster of temporary pools
Authors: Tuytens Karen , Vanschoenwinkel Bram , Waterkeyn Aline , Brendonck Luc 
Published: February 2014

Summary

Future moderate changes in evaporation and precipitation regimes could have pronounced effects on zooplankton populations in small and temporary aquatic habitats, by causing higher salinity and a shorter wet phase and by reducing passive dispersal via hydrological connections between pools and increasing it by exposing propagules to the wind.

Using a hydrological model, we simulated various climate change scenarios in a natural cluster of temporary rock pools in South Africa.

In our simulations, a shift towards a drier climate was associated with reduced permanence and increased conductivity, resulting in a lower percentage of inundations sufficient for the hatching, growth and reproduction of aquatic organisms (up to a 21% decline for a fairy shrimp). Connections between pools by overflowing occurred less frequently (by up to 28%). However, more frequent desiccation events (by up to 15%) led to increased exposure of dormant propagules to wind, possibly promoting dispersal within the pool cluster but also leading to losses from the propagule bank.

Our results suggest that environmental change might not only affect local (within‐pool) selection pressures but also regional dynamics in rock pool metapopulations and communities.
PPARγ gene polymorphism, C‐reactive protein level, BMI and periodontitis in post‐menopausal Japanese women
Authors: Wang Yangming , Sugita Noriko , Yoshihara Akihiro , Iwasaki Masanori , Miyazaki Hideo , Nakamura Kazutoshi , Yoshie Hiromasa 
Published: February 2014

BackgroundSeveral studies have reported inconsistent results regarding the association between the PPARγPro12Ala polymorphism and obesity. Obese individuals had higher C‐reactive protein (CRP) levels compared with those of normal weight, and PPARγ activation could significantly reduce serum high‐sensitive CRP level. We have previously suggested that the Pro12Ala polymorphism represents a susceptibility factor for periodontitis, which is a known risk factor for increased CRP level.ObjectivesThe aim was to investigate associations between PPARγ gene polymorphism, serum CRP level, BMI and/or periodontitis among post‐menopausal Japanese women.Materials and methodsThe final sample in this study comprised 359 post‐menopausal Japanese women. Periodontal parameters, including PD, CAL and BOP, were measured per tooth. PPARγPro12Ala genotype was determined by PCR‐RFLP. Hs‐CRP value was measured by a latex nephelometry assay.ResultsNo significant differences in age, BMI or periodontal parameters were found between the genotypes. The percentages of sites with PD ≥ 4 mm were significantly higher among the hsCRP ≥ 1 mg/l group than the hsCRP < 1 mg/l group (p = 0.003). Positive correlations were found between serum hsCRP levels and the percentages of sites with PD ≥ 4 mm (p = 0.043) in PPARγ Ala allele carriers, and BMI (p = 0.033) in non‐carriers. After adjustment for model covariates, BMI was significantly associated with serum hsCRP level.ConclusionThe PPARγPro12Ala polymorphism was not independently associated with periodontitis, serum CRP level or BMI in post‐menopausal Japanese women. However, serum hsCRP level correlated with periodontitis in Ala allele carriers, and with BMI in non‐carriers.
Review of findings in prophylactic gynaecological specimens in Lynch syndrome with literature review and recommendations for grossing
Authors: Downes Michelle R , Allo Ghassan , McCluggage W Glenn , Sy Keiyan , Ferguson Sarah E , Aronson Melyssa , Pollett Aaron , Gallinger Steve , Bilbily Elaine , Shaw Pat , Clarke Blaise A 
Published: February 2014

AimsProphylactic hysterectomy with bilateral salpingo‐oophorectomy is being increasingly undertaken in patients with Lynch syndrome (LS). The pathological features in such specimens are not well described and, unlike the SEE‐FIM protocol for salpingo‐oophorectomy specimens in BRCA1/2 mutation carriers and the gastrectomy grossing protocols for patients with CDH1 (E‐cadherin) mutations, guidelines have not been devised for the grossing of prophylactic gynaecological specimens from LS patients. We aimed to review the pathological findings in a series of prophylactic gynaecological specimens from LS patients and develop guidelines for the grossing of these specimens.Methods and resultsWe reviewed the pathological findings in 25 prophylactic gynaecological specimens from LS patients and audited the grossing protocols in different centres across Ontario, Canada. We found a 32% incidence of endometrial carcinoma or a precursor lesion; the two endometrial cancers identified were low‐grade, low‐stage endometrioid adenocarcinomas. To address the absence of guidelines for pathological examination, we undertook a literature review of gynaecological malignancies and incidental findings in prophylactic specimens in LS patients.ConclusionWe provide recommendations regarding the grossing of such specimens which includes in‐toto examination of the lower uterine segment, endometrium, ovaries and fallopian tubes with representative sampling of the cervix.