bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vivo Imaging of NF-κB Activity, Pain Sensitivity, and Serum Cytokines in a Rodent Model of Neuropathy
Authors: Setton Lori A , Kraus Virginia B , Bowles Robby D. 
Published: May 2014

Herniation of the intervertebral disc may be associated with a painful neuropathy (sciatica) or motor weakness that is partly mediated by inflammatory cell infiltration and proinflammatory cytokine expression. Much of the cytokine-mediated signaling and inflammatory events falls downstream of activation of the transcription factor, NF- κB. We have previously demonstrated an ability to visualize NF- κB activity in a transgenic NF-κB luciferase reporter mouse, following induction of arthritis in the knee joint.1 The temporal and spatial pattern of NF-κB-luc correlated with development of painful sensitivities in the arthritis model suggesting an ability to use in vivo imaging to rapidly screen progression of pathology and therapeutic interventions. Here, we investigate the temporal and spatial development of NF-κB activity in the NF-κB-luc reporter mouse following induction of peripheral nerve injury (sciatic nerve constriction) and test for relationships amongst pain-related sensitivities, serum levels of NF-κB-related cytokines, and regional measures of NF-κB activity. Our work in this model system revealed that NF-κB B activity following nerve injury is elevated in the region of the affected nerve, with luciferase production specifically from the sciatic nerve and the surrounding musculature. Temporal elevations in NF-κB activity were noted beginning at 3 days after surgery, and correlated with mechanical (von Frey testing, Spearman ρ-0.84) and thermal (hyperalgesia at paw, Spearman ρ -0.80) sensitivity in a distinctly nonlinear fashion. NF- κB activity also correlated with serum interleukin 6 levels (Spearman ρ 0.75), but not with other measured cytokines. Delivery of the NF- κB specific inhibitor, NEMO-binding domain peptide NBD, was able to reduce NF- κB-luc signal, restore thermal sensitivity to sham levels, and restore mechanical sensitivity to near sham levels. These findings are important for demonstrating a direct link between the NF- κB-luc signal and pain-related measures. Together this work suggests that longitudinal and spatially resolved in vivo imaging can be useful to characterize cytokine-related sensitivities in neuropathy, with implications for radiculopathy associated with intervertebral disc herniation. Disclosure of Interest None declared Reference Bowles RD, Mata BA, Bell RD, et al. In vivo luminescent imaging of NF-κB activity and serum cytokine levels predict pain sensitivities in a rodent model of osteoarthritis. Arthritis Rheum 2013; November 18 (Epub ahead of print); doi: 10.1002/art.38279
Roles of Biomaterials in Cell-based Therapies for Disc Degeneration
Authors: Chan Barbara 
Published: May 2014

Degenerative disc disease poses an increasing threat to our quality of life as we age. Existing treatments have limitations. New treatment modalities using biological approaches are appealing. While cells including mesenchymal stem cells (MSC) are proving themselves potential candidates for treating disc degeneration, biomaterials are demonstrating their important roles in supporting and potentiating such therapies. During intradiscal injection, the vast majority of cells leaked out via back flow from the injection portal, reducing the efficacy of treatment. Recent evidence even suggests that annulus puncture is associated with cell leakage and contributes to osteophyte formation, leading to an undesirable side-effect of MSC-based therapy. This suggests the significance of developing appropriate cell carriers and effective approaches to prevent leakage and associated osteophyte formation before MSC-based therapies can be applied in a clinical setting. Using a collagen microencapsulation platform, we fabricated collagen microspheres entrapping MSCs, supporting their survival, proliferation, differentiation and matrix remodeling. Using a rabbit disc degeneration model, we showed that, comparing with delivering MSC in saline, delivering MSC in collagen microspheres significantly reduced the risk of osteophyte formation. Using a photochemical crosslinking technology, we further fabricated an injectable collagen-based annulus plug to block the injection portal during intradiscal delivery. Ex vivo studies showed that the plug survived physiologically relevant loadings and significantly reduced leakage and enhanced retention of the injected materials. In vivo rabbit disc degeneration model showed that the plug significantly reduced osteophyte formation, suggesting the potential of the annulus plug as an adjunct or annulus closure device for intradisc delivery of cells and materials. Apart from facilitating cell delivery as shown in the above mentioned example, biomaterials play important roles in immobilizing soluble signals such as growth factors, providing structural and mechanical support to cells and tissues, presenting microenvironmental clues or niches, and acting as the template for functional remodeling of cells and tissues. Detailed discussion and examples on these functions of biomaterials will be given in this study. Disclosure of Interest None declared
LINK between Degeneration and Regeneration of Human Intervertebral Discs
Authors: Mwale Fackson , Gawri Rahul , Ouellet Jean , Önnerfjord Patrik , Alkhatib Bashar , Steffen Thomas , Heinegård Dick , Roughley Peter , Antoniou John , Haglund Lisbet 
Published: May 2014

Back pain affects a large portion of the population across all ages and intervertebral disc (IVD) degeneration is its most implicated common cause. Presently, there are no established treatments to prevent, stop, or even retard disc degeneration, and surgery is often the offered option. Previous studies have shown that Link N can act as a growth factor and stimulate the synthesis of proteoglycans and collagens in bovine IVD in vitro and in intact human IVDs ex vivo, as well as increase disc height in a rabbit model of disc degeneration. However, the sequences in Link N involved in modulating cellular activity are not well understood. To determine if disc cells can proteolytically process Link N, human disc cells in monolayer were exposed to native Link N over a 48-hour period and mass spectrometric analysis revealed that a peptide spanning residues 1 to 8 was generated in the presence of AF cells but not NP cells. Link N 1-8 significantly induced proteoglycan production in the presence of IL-1β in both NP and AF cells, confirming that the biological effect is maintained in the first eight amino acids of the peptide and indicating that the effect is sustained in an inflammatory environment. Thus Link N 1-8 could be a promising candidate for biologically induced disc repair, and the identification of such a stable specific peptide may facilitate the design of compounds to promote disc repair and provide alternatives to surgical intervention for early stage disc degeneration. Acknowledgments The authors thank Ms. Areej Khabut for her assistance with mass spectrometry. This work would not have been possible without funding from the Faculty of Medicine McGill University, AO Spine, North American Spine Society and Canadian Institutes of Health Research. We also thank Transplant Quebec for coordinating the retrieval of human lumbar spines through their organ donation program. Lastly, we thank The Crafoord Foundation and the Inga-Britt & Arne Lundberg Foundation for funding the mass spectrometers used in this study. Disclosure of Interest None declared
Pulsed Electromagnetic Field Stimulation of Intervertebral Disc Cells
Authors: Ferguson Stephen J. , Franco-Obregón Alfredo , Wuertz Karin 
Published: May 2014

Pulsed electromagnetic field (PEMF) stimulation has been proposed for the noninvasive treatment of a variety of musculoskeletal disorders. PEMF is most commonly applied in the treatment of fracture nonunions or delayed fusion. PEMF stimulation devices are FDA approved as a complimentary therapy and there is clinical evidence of effectiveness for bone stimulation. More recently, potential therapeutic effects of PEMF on muscle and cartilage have been reported, with also an increasing interest in the application for the treatment of disc disorders. We have studied the influence of PEMFs in the mT range on isolated intervertebral disc cells in both 2D monolayer and 3D cell culture models, exploring the influence of parameters such as field strength, pulsing frequency, and daily exposure. Depending on the nature of the PEMF stimulation, we have demonstrated a mild anabolic effect, mostly of mitogenic nature, and also the potential to decrease the expression of catabolic enzymes, including matrix metalloproteinases and aggrecanases. A full and detailed understanding of the pathway(s) by which PEMFs influence cellular metabolism remains the topic of current investigations. Information on the optimal strategy for PEMF stimulation of the IVD is scarce. BMP-2 has been shown to mediate the response of disc cells to PEMF, suggesting a potential benefit of combined therapy. However, in vitro studies have also highlighted the highly variable nature of the response of disc cells to PEMF stimulation. Further work is required to elucidate the optimal parameters for PEMF therapy, to validate the process in vivo before translating the process to clinical practice. Disclosure of Interest None declared
Connectivity and critical current density of in-situ processed MgB2 superconductors: Effect of excess Mg and non-carbon based additives
Authors: Bhadauria P. P. S. , Gupta Anurag , Kishan Hari , Narlikar A. V. 
Published: May 2014

In a sequel to our previous paper (J. Appl. Phys. 113, 036908 (2013)), where we reported comprehensive analysis of inter-grain connectivity (AF), pinning, percolation threshold (Pc), and anisotropy (γ) in a series of ex-situ processed MgB2, we address the same issues in in-situ processed samples. MgB2 samples with stoichiometric composition, excess Mg (5 wt. %) and further 3 wt. % addition of various non-carbon based additives like nano-Ag, nano-Ni, and YBCO are synthesised by the in-situ route. Detailed investigations of X-ray diffraction, magnetization (M), and resistivity (ρ) as a function of temperature (T) and field (B) in the range 5–300 K and 0–8 T are carried out in all the samples. The resistive superconducting onset Tcon ∼ 38.6 ± 0.3 K and offset (where ρ goes to zero) Tc0 ∼ 38.1 ± 0.3 K of the samples stay nearly unchanged. The inter-grain connectivity (AF) of the samples varies between 11%–20%. All the additives result in a critical current density (Jc) higher than the stoichiometric MgB2 sample, where the highest values (e.g., Jc(1 T, 5 K) ∼ 1.2 × 109 A/m2) are observed for the sample with 5 wt. % excess Mg. The major findings based on quantitative analysis of ρ (T, B) and Jc (B, T) data in all the samples are: (1) along with previously studied ex-situ samples, the Jc(AF) shows a significant increase at AF ∼ 7%; (2) the irreversibility lines lie lower than the characteristic Tc0(B) lines in the B-T phase diagram; (3) a universal core pinning (δl- and/or δTc- type) mechanism is revealed in the entire T range 5–30 K; and (4) typical values of Pc ∼ 0.57 ± 0.04 is indicative of weak link networks.
Tracking of intertissue migration reveals the origins of tumor-infiltrating monocytes
Authors: Shand Francis H. W. , Ueha Satoshi , Otsuji Mikiya , Koid Suang Suang , Shichino Shigeyuki , Tsukui Tatsuya , Kosugi-Kanaya Mizuha , Abe Jun , Tomura Michio , Ziogas James , Matsushima Kouji 
Published: May 2014

Significance
Solid tumors contain large numbers of immune cells, including monocytes and monocyte-derived macrophages that promote tumor progression. During tumor development, monocytes accumulate in the spleen. However, the influence of spleen cells on tumor growth remains controversial. Here, we used novel methods for tracking intertissue migration and monitoring hematopoiesis to show that during tumor development the bone marrow dramatically accelerates production of monocytes, rapidly transferring many of these newly formed cells to a reservoir in the spleen. However, these spleen monocytes are less able than their bone marrow counterparts to enter the tumor and make only a minor contribution to the tumor-infiltrating monocyte population. These findings clarify the roles of the spleen and bone marrow in cancer development.
Prescribing mobility scooters in Australia: Occupational therapists' narratives
Authors: Maywald Anita , Stanley Mandy 
Published: May 2014

Background/aimIn order for older people to remain active and engaged as they age they need to be mobile in the community. One way of maintaining community mobility is through the use of a mobility scooter. Occupational therapists are key health professionals involved with assessing for mobility scooters yet minimal research exists into the experience. This study sought to explore occupational therapists' experiences of assessing for mobility scooters to older people in Australia.MethodsA qualitative study was undertaken in which narratives were solicited from 18 occupational therapists involved in scooter assessment to people aged 65 or over. Interview data were analysed following narrative analysis guidelines.ResultsAnalysis revealed six predominant narratives ranging from two success stories to the narrative of disempowerment and stories of negotiating risk. Experienced therapists had more resources and skills to draw on to manage the complexity of prescription and negotiation of risk.ConclusionsFindings from this study suggest that novices or those new to mobility scooter prescription need to access supervision and support to improve the chances of having a successful outcome. Further exploration of how therapists manage situations of vulnerability and risk is warranted to prevent burnout for therapists and reduce the likelihood of restricting clients' occupational potential. Continuing professional development activities are also recommended.
Oestrogen compromises the facilitatory effect of chronic nicotine on adenosine A2B receptor–K+ channel‐mediated renal vasodilation
Authors: El‐Mas Mahmoud M , El‐Gowilly Sahar M , Elsalakawy Lamia K , El‐Gowelli Hanan M 
Published: May 2014

SummaryWe have shown previously that the renal vasodilatory action of the adenosine analogue 5′‐N‐ethylcarboxamidoadenosine (NECA) in female rats is mediated via preferential activation of adenosine A2B receptor (A2BR)–K+ channel signalling. In the present study, we tested the hypothesis that the renal vasodilatory effect of NECA and its A2BR/K+ channel specificities are altered by chronic nicotine administration. The oestrogenic modulation of the nicotine–NECA renovascular interaction was also evaluated by determining the effect of ovariectomy (OVX) and oestrogen replacement (OVXE2) on the evoked responses. In isolated phenylephrine‐preconstricted perfused kidneys obtained from sham‐operated rats, vasodilation in response to cumulative bolus injections of NECA (1.6–50 nmol) or papaverine (1–243 nmol) were not affected by nicotine (1–8 mg/kg per day, i.p., 2 weeks). However, vasodilator responses to NECA, but not papaverine, were reduced in kidneys of OVX rats and restored to near‐sham values after E2 replacement. Further, nicotine increased NECA‐induced vasodilation in perfused kidneys from OVX rats, but failed to do so in OVXE2 preparations. The enhanced NECA responsiveness in nicotine‐treated OVX preparations was abolished after infusion (into isolated kidneys) of 10 μmol/L alloxazine (A2BR antagonist) or BaCl2 plus glibenclamide (blockers of inward rectifier and ATP‐sensitive K+ channels, respectively). Vasodilator responses to 0.05–1.6 μmol minoxidil (a K+ channel opener) were increased by nicotine in OVX, but not OVXE2, preparations and this increase was abolished after infusion of BaCl2 + glibenclamide. Together, the data suggest that chronic nicotine enhances A2BR/K+ channel‐mediated renal vasodilation in oestrogen‐depleted rats.
Vildagliptin added to sulfonylurea improves glycemic control without hypoglycemia and weight gain in Chinese patients with type 2 diabetes mellitus 中国2型糖尿病患者使用磺脲类药物联合维格列汀可改善血糖控制且无低血糖及体重增加
Authors: Yang Wenying , Xing Xiaoping , Lv Xiaofeng , Li Yiming , Ma Jianhua , Yuan Guoyue , Sun Feifei , Wang Wei , Woloschak Michael , Lukashevich Valentina , Kozlovski Plamen , Kothny Wolfgang ,   all investigators
Published: May 2014

AbstractObjectiveThe aim of the present study was to assess the efficacy and safety of vildagliptin as add‐on to sulfonylurea therapy in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on sulfonylurea monotherapy.MethodsThe 24‐week randomized double‐blind placebo‐controlled study compared vildagliptin 50 mg, q.d., with placebo as add‐on to glimepiride in T2DM patients who were inadequately controlled (HbA1c 7.5%–11.0% [58–97 mmol/mol]) on a stable dose of sulfonylurea for ≥12 weeks before study entry.ResultsIn all, 279 patients were randomized to receive either vildagliptin (n = 143) or placebo (n = 136). At baseline, overall mean age was 58.5 years, body weight 68.1 kg, duration of diabetes 6.9 years and daily glimepiride dose 3.3 mg. After 24 weeks, the adjusted mean change (AMΔ) in HbA1c was −0.7% (−8 mmol/mol; baseline 8.6%, 70 mmol/mol) in the vildagliptin group and −0.2% (−2 mmol/mol; baseline 8.7%, 72 mmol/mol) in the placebo group, with a treatment difference of −0.5% (−5 mmol/mol; P < 0.001). The between‐group difference in AMΔ in fasting plasma glucose was −0.4 mmol/L (P = 0.160). There was a slight, but not significant, decrease in body weight in both groups. No hypoglycemic events were reported in either group, including those patients reaching HbA1c <7.0%. Patients in the vildagliptin and placebo groups reported low and comparable incidences of adverse events (14.0% vs 17.8%) and serious adverse events (0.7% in each group).ConclusionVildagliptin 50 mg, q.d., added to sulfonylurea monotherapy is effective in Chinese patients with T2DM, without increasing the risk of hypoglycemia and weight gain.
Who under‐reports their alcohol consumption in telephone surveys and by how much? An application of the ‘yesterday method’ in a national Canadian substance use survey
Authors: Stockwell Tim , Zhao Jinhui , Macdonald Scott 
Published: May 2014

AbstractBackground and AimsAdjustments for under‐reporting in alcohol surveys have been used in epidemiological and policy studies which assume that all drinkers underestimate their consumption equally. This study aims to describe a method of estimating how under‐reporting of alcohol consumption might vary by age, gender and consumption level.MethodThe Canadian Alcohol and Drug Use Monitoring Survey (CADUMS) 2008–10 (n = 43 371) asks about beverage‐specific ‘yesterday’ consumption (BSY) and quantity–frequency (QF). Observed drinking frequencies for different age and gender groups were calculated from BSY and used to correct values of F in QF. Beverage‐specific correction factors for quantity (Q) were calculated by comparing consumption estimated from BSY with sales data.ResultsDrinking frequency was underestimated by males (Z = 24.62, P < 0.001) and females (Z = 17.46, P < 0.001) in the QF as assessed by comparing with frequency and quantity of yesterday drinking. Spirits consumption was underestimated by 65.94% compared with sales data, wine by 38.35% and beer by 49.02%. After adjusting Q and F values accordingly, regression analysis found alcohol consumption to be underestimated significantly more by younger drinkers (e.g. 82.9 ± 1.19% for underage drinkers versus 70.38 ± 1.54% for those 65+, P < 0.001) and by low‐risk more than high‐risk drinkers (76.25 ± 0.34% versus 49.22 ± 3.01%, P < 0.001). Under‐reporting did not differ by gender.ConclusionsAlcohol consumption surveys can use the beverage‐specific ‘yesterday method’ to correct for under‐reporting of consumption among subgroups. Alcohol consumption among Canadians appears to be under‐reported to an equal degree by men and women. Younger drinkers under‐report alcohol consumption to a greater degree than do older drinkers, while low‐risk drinkers underestimate more than do medium and high‐risk drinkers.
The importance of underground shelter resources for reptiles in dryland landscapes: A woma python case study
Authors: Bruton Melissa J. , McAlpine Clive A. , Smith Andrew G. , Franklin Craig E. 
Published: May 2014

AbstractFor effective fauna conservation and management, ecologists are required to identify the resources that are critical for species to survive, and consider how these are distributed across landscapes. The critical resources usually considered are food and water, but the availability of appropriate shelter resources can be a key driver of habitat suitability for terrestrial reptiles and amphibians. Reptiles are important components of dryland ecosystems, yet we have little understanding about how anthropogenic disturbances affect the availability of shelter resources and reptile survival in drylands. In this study, we used VHF radio‐tracking to assess the importance of shelter resources in determining the habitat use patterns of a Near‐Threatened reptile species, the woma (Aspidites ramsayi; Pythonidae), in modified and intact dryland landscapes of Queensland, Australia. We compared the structural and thermal attributes of locations that were used, with those that were available. Using an information‐theoretic approach, we found that the occurrence of womas was strongly associated with the presence of ground burrows, which are excellent thermal insulators. No other shelter type was capable of buffering our study species from sub‐zero temperatures during winter, although summer temperatures of >40°C were buffered by hollow logs and piles of woody debris. Habitat use patterns were influenced more by the occurrence of underground shelters than by habitat type. Clearing status per se (cleared, regrowth or intact) had minimal influence on occurrence. Thermally buffered underground shelters are a vital resource for our focal species, and the availability of this shelter resource drives habitat suitability in modified dryland landscapes. Due to the key trophic role of reptiles in dryland ecosystems, and the excellent thermal buffering capacity of underground shelters, we propose that ground burrows may be potentially considered as keystone structures in drylands, and require a similar level of protection to ‘habitat’ or ‘legacy’ trees in forested ecosystems.
General anaesthetics and the developing brain: an overview
Authors: Sinner B. , Becke K. , Engelhard K. 
Published: May 2014

SummaryVarious experimental studies in animals have shown that general anaesthetics are potentially toxic to the developing brain. By inducing apoptosis or interfering with neurogenesis, anaesthetic exposure during a critical period of neuronal development can have significant impact on neurocognitive function later in life. It remains controversial whether these experimental results can be transferred to human beings and this is under intensive scientific evaluation. To gain more insight into possible neurotoxic effects on the human brain of infants and small children, a number of retrospective studies have been performed. At present, there is no clear evidence that exposure to anaesthesia up to the age of 3–4 years is associated with neurocognitive or behavioural deficits. Currently, the PANDA, MASK and GAS studies are underway to explore this relationship. Anaesthesia is not an end in itself, but necessary to facilitate surgical procedures. There is evidence that maintaining physiological conditions is important for the overall outcome following anaesthesia and surgery. Until proven otherwise, it can be recommended to keep anaesthesia and surgery as short as possible, to use short‐acting drugs and/or a combination of general anaesthesia and multimodal pain therapy including systemic analgesics, and local or regional anaesthesia, to reduce the overall drug dosage.