Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
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Πέμπτη 25 Μαΐου 2017
Differential Motivations for Pursuing Diagnostic Radiology by Gender
Source:Academic Radiology
Author(s): Lars J. Grimm, Dorothy A. Lowell, Sarah W. Cater, Sora C. Yoon
Rationale and ObjectivesThe purpose of this study is to determine how the motivations to pursue a career in radiology differ by gender. In addition, the influence of medical school radiology education will be assessed.Materials and MethodsRadiology applicants to our institution from the 2015–2016 interview season were offered an online survey in February 2016. Respondents scored the influence of 24 aspects of radiology on their decision to pursue radiology. Comparisons were made between male and female respondents. Respondents were also asked the type of medical school radiology education they received and to score the influence this experience had on their decision to pursue radiology.ResultsThere were 202 total respondents (202/657) including 47 women and 155 men. Compared to men, the following factors had a more negative impact on women: flexible work hours (P = 0.04), work environment (P = 0.04), lifestyle (P = 0.04), impact on patient care (P = 0.05), high current debt load (P = 0.02), gender distribution of the field (P = 0.04), and use of emerging/advanced technology (P = 0.02). In contrast, women felt more favorably about the opportunities for leadership (P = 0.04) and research (P < 0.01).Dedicated radiology exposure was as follows: 20% (n = 20) none, 48% (n = 96) preclinical exposure, 55% (n = 111) elective rotation, and 18% (n = 37) core rotation. More intensive radiology exposure via a core rotation had a significantly positive impact on the decision to pursue radiology (P < 0.01).ConclusionsMale and female radiology applicants are motivated by different aspects of radiology, which may influence residency recruitment practices. In addition, more intensive radiology exposure has a net positive impact on the decision to pursue radiology.
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Synthesis and study of nanostructured Ce-Zr-La-RE-O (RE=Y, Nd and Pr) quaternary solid solutions and their supported three-way catalysts
Publication date: 15 September 2017
Source:Materials & Design, Volume 130
Author(s): Yi Zhou, Jie Deng, Lei Xiong, Jianli Wang, Shandong Yuan, Hailong Zhang, Yaoqiang Chen
In this work, a series of nanostructured Ce-Zr-La-RE-O (RE=Y, Nd and Pr) quaternary solid solutions (CZLY, CZLN and CZLP) were synthesized via simultaneous co-precipitation with the assistance of lauric acid. The corresponding supported Pd-only three-way catalysts (Pd/CZLY, Pd/CZLN and Pd/CZLP) were also prepared by wet-impregnation method. The effects of Y, Nd and Pr on CeO2-ZrO2-La2O3-RE2O3 system and corresponding supported Pd-only three-way catalysts were investigated by X-ray diffraction (XRD), Raman, hydrogen-temperature programmed reduction (H2-TPR), N2 adsorption-desorption and X-ray photoelectron spectroscopy (XPS) characterizations. The results show that all the fresh samples form single phase structure, however, after being thermal aged at 1000°C, CZLN-a exhibits the best thermal stability which presents a remarkably low reduction peak temperature of 395°C and a high surface area of 42.6m2/g. The study of the interactions between Pd metal particles and supports indicates that Pd could selectively adsorb onto the surface Ce sites of different supporting materials by forming different chemical bonds. Pd/CZLN also exhibits superior three-way catalytic activity with respect to others, particularly, the light-off temperatures (T50) of C3H8, CO and NO for Pd/CZLN-a are as low as 339, 175 and 198°C, respectively.
Graphical abstract
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Partitioning and diffusion of transition metal solutes in ternary model Ni-based single crystal superalloys
Publication date: 15 September 2017
Source:Materials & Design, Volume 130
Author(s): Shaohua Liu, Minru Wen, Zi Li, Wenqing Liu, Ping Yan, Chongyu Wang
Partitioning and diffusion of transition metal solutes can significantly affect the coarsening rate of γ′ precipitates in Ni-based single crystal superalloys. Using first-principles density-functional calculations and atom probe tomography, we investigated the partitioning coefficient and diffusion rate of 3d (TiNi), 4d (ZrPd), and 5d (HfPt) transition metal solutes. For ternary model Ni-based single crystal superalloys, the 3d solutes (except Ti) partition to the matrix phase, whereas 4d and 5d solutes (except Ru, Rh, and Ir) prefer γ′ precipitates. The existing atom probe tomography results are consistent with the calculation results. Across the periodic table, middle-row elements have a higher (lower) diffusion activation energy (diffusion rate) than early and late row elements. The band-filling effect that is coupled with electronic structure analysis can explain the parabolic behavior of energetics that involves bond breaking. To minimize the coarsening rate, we have screened alloying elements that both have a low diffusion rate in the γ matrix and partition to the γ′ phase. These alloying elements will suppress the coarsening behavior of the precipitates and are expected to contribute to the stability of precipitates at elevated temperature.
Graphical abstract
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Effects of annealing on microstructure and deformation uniformity of Ti-22Al-24Nb-0.5Mo laser-welded joints
Publication date: 15 September 2017
Source:Materials & Design, Volume 130
Author(s): Xueyan Jiao, Beibei Kong, Wang Tao, Gang Liu, Hanwei Ning
In order to improve the deformation uniformity between base metal and weld zone, the laser-welded joints of Ti-22Al-24Nb-0.5Mo alloy were subjected to different annealing treatments at 980°C, 1030°C and 1080°C, respectively. The microstructure and tensile behavior of the joints under as-welded and annealed conditions were systematically investigated. Results show that the microstructure and mechanical properties of the laser-welded joints are found sensitive to the annealing conditions. During the annealing processes, the static recrystallization of B2 phase occurred in base metal with the phase transformations from O to B2 and α2 to B2. In fusion zone, the α2 phase precipitated within the columnar B2 grains except the annealing at 1080°C. The microstructural inhomogeneity between base metal and weld zone has been effectively reduced by the annealing above 1030°C. Besides, the tensile tests at 970°C reveal that annealing treatment has significantly improved the deformation uniformity in weld joints, for example the maximum deviation rate from average effective strain for the joints annealed at 1030°C was reduced to 0.15. Overall, the annealing process at 1030°C is suggested as the appropriate heat treatment to obtain the uniform deformability in laser-welded joints.
Graphical abstract
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Flu-like illness, fever, malaise and chills, followed by severe nonpleuritic chest pain and shortness of breath
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
Neglected Australian arboviruses: quam gravis?
Source:Microbes and Infection
Author(s): Narayan Gyawali, Richard S. Bradbury, John G. Aaskov, Andrew W. Taylor-Robinson
At least 75 arboviruses have been identified from Australia. Most have a zoonotic transmission cycle, maintained in the environment by cycling between arthropod vectors and susceptible mammalian or avian hosts. The primary arboviruses that cause human disease in Australia are Ross River, Barmah Forest, Murray Valley encephalitis, Kunjin and dengue. Several other arboviruses are associated with human disease but little is known about their clinical course and diagnostic testing is not routinely available. Given the significant prevalence of undifferentiated febrile illness in Australia, investigation of the potential threat to public health presented by these viruses is required.
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Chronicles of a reductase: Biochemistry, genetics and physio-pathological role of GSNOR
Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Salvatore Rizza, Giuseppe Filomeni
S-nitrosylation is a major redox posttranslational modification involved in cell signaling. The steady state concentration of S-nitrosylated proteins depends on the balance between the relative ability to generate nitric oxide (NO) via NO synthase and to reduce nitrosothiols by denitrosylases. Numerous works have been published in last decades regarding the role of NO and S-nitrosylation in the regulation of protein structure and function, and in driving cellular activities in vertebrates. Notwithstanding an increasing number of observations indicates that impairment of denitrosylation equally affects cellular homeostasis, there is still no report providing comprehensive knowledge on the impact that denitrosylation has on maintaining correct physiological processes and organ activities.Among denitrosylases, S-nitrosoglutathione reductase (GSNOR) represents the prototype enzyme to disclose how denitrosylation plays a crucial role in tuning NO-bioactivity and how much it deeply impacts on cell homeostasis and human patho-physiology.In this review we attempt to illustrate the history of GSNOR discovery and provide the evidence so far reported in support of GSNOR implications in development and human disease.
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Cyclophosphamide and acrolein induced oxidative stress leading to deterioration of metaphase II mouse oocyte quality
Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Roohi Jeelani, Sana N. Khan, Faten Shaeib, Hamid-Reza Kohan-Ghadr, Sarah R. Aldhaheri, Tohid Najafi, Mili Thakur, Robert Morris, Husam M. Abu-Soud
Cyclophosphamide (CTX) is a chemotherapeutic agent widely used to treat ovarian, breast, and hematological cancers as well as autoimmune disorders. Such chemotherapy is associated with reproductive failure and premature ovarian insufficiency. The mechanism by which CTX and/or its main metabolite, acrolein, affect female fertility remains unclear, but it is thought to be caused by an overproduction of reactive oxygen species (ROS). Here, we investigated the effect of CTX on metaphase II mouse oocytes obtained from treated animals (120mg/kg, 24h of single treatment), and oocytes directly exposed to increasing concentrations of CTX and acrolein (n=480; 0, 5, 10, 25, 50, and 100μM) with and without cumulus cells (CCs) for 45min which correlates to the time of maximum peak plasma concentrations after administration. Oocytes were fixed and subjected to indirect immunofluorescence and were scored based on microtubule spindle structure (MT) and chromosomal alignment (CH). Generation of ROS was evaluated using the Cellular Reactive Oxygen Species Detection Assay Kit. Deterioration of oocyte quality was noted when oocytes were obtained from CTX treated mice along with CTX and acrolein treated oocytes in a dose-dependent manner as shown by an increase in poor scores. Acrolein had an impact at a significantly lower level as compared to CTX, plateau at 10μM versus 50μM, respectively. These variation is are associated with the higher amount of ROS generated with acrolein exposure as compared to CTX (p<0.05). Utilization of antioxidant therapy and acrolein scavengers may mitigate the damaging effects of these compounds and help women undergoing such treatment.
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A Phase II Study of Everolimus Plus Oral Prednisone in Patients with Metastatic Renal Cell Cancer
Lessons Learned.
The combination of everolimus and low-dose prednisone administered daily was hypothesized to prevent noninfectious pneumonitis (NIP) and mucositis, two common adverse events related to everolimus. Although mucositis was detected in only one case, all-grade NIP occurred in four of eight cases (50%), and this was considered enough to stop accrual of the study.
These data suggest the need for careful monitoring of patients receiving everolimus who are treated with corticosteroids.
Background.Everolimus is standard of care in the treatment of patients affected by metastatic renal cell carcinoma (mRCC) that has progressed after at least one previous line of treatment. Stomatitis and noninfectious pneumonitis (NIP) are common adverse events (AEs) in patients treated with everolimus. Prednisone could reduce the incidence of stomatitis, and it is commonly used to treat NIP. We hypothesized that low doses of prednisone could reduce the incidence and/or the severity of everolimus-induced NIP and stomatitis.
Methods.We have conducted an open-label, single-arm, phase II trial of prednisone 5 mg b.i.d. added to everolimus 10 mg/day in patients with mRCC. We planned to evaluate the safety, tolerability, and activity of this combination in mRCC patients. We aimed to reduce incidence of drug discontinuations due to stomatitis or NIP from 25% to 10%.
Results.Three (38%) of the first eight patients enrolled experienced grade ≥2 pneumonitis and stopped treatment. Grade 1 stomatitis occurred in only one patient (13%). Five of eight patients experienced disease progression at the 2-month evaluation. Two patients (25%) were reported free of disease progression at 1 year of treatment.
Conclusion.The incidence of NIP in these patients was considered too high for completing accrual of this study. These results may be of interest for investigating the pathogenesis of NIP and suggest that patients should be carefully followed if treated with chronic corticosteroids while receiving everolimus. The Oncologist 2017;22:1–8
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Alternative Donor Graft Sources for Adults with Hematologic Malignancies: A Donor for All Patients in 2017!
Hematopoietic stem cell transplant (HSCT) is potentially curative for a wide variety of malignant diseases, including acute and leukemias, lymphoma, and myelodysplasia. Choice of a stem cell donor is dependent on donor availability, donor compatibility and health, recipient disease type, and recipient condition. Current sources of stem cell donation for HSCT are matched sibling donors (MSDs), matched unrelated donors (MUDs), 1-antigen mismatched unrelated donors (MMUDs), haploidentical donors (haplo), and umbilical cord blood (UCB) units. Historically, preferred donors for HSCT have been human leukocyte antigen (HLA)-matched sibling donors; however, only about 30% of U.S. patients will have a MSD available. The majority of patients referred for HSCT will require an alternative donor graft: MUD, MMUD, UCB, or haplo. The likelihood of finding a MUD varies depending on the ethnicity of the recipient. White Caucasians of European descent have the greatest chance of finding a MUD. Chances of finding a MUD are significantly less for African-American or Hispanic recipients due to HLA polymorphisms. Therefore, MMUD, UCB, and haplo donor graft sources expand the donor pool for recipients who do not have a MSD or MUD available. Given the variety of different donor stem cell sources available today, nearly every patient who needs an allogeneic HSCT has a potential donor in 2017. All transplant-eligible patients with hematologic malignancies should be evaluated by a transplant center to determine if HSCT is a viable treatment option for their underlying disease process. The Oncologist 2017;22:1–10
Implications for Practice.The goal of this review is to increase the awareness of oncology practitioners to the availability of alternative donor stem cell transplants for patients with hematologic malignancies. Despite new agents, stem cell transplant remains the only curative therapy for many patients with acute and chronic leukemia, myelodysplasia, and lymphoma. Given the variety of different donor stem cell sources available today, nearly every patient who needs an allogeneic stem cell transplant will have a donor.
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Default Rules Are Better Than Active Choosing (Often)
Publication date: Available online 25 May 2017
Source:Trends in Cognitive Sciences
Author(s): Cass R. Sunstein
In recent years, governments have become keenly interested in behavioral science; new findings in psychology and behavioral economics have led to bold initiatives in areas that involve poverty, consumer protection, savings, health, the environment, and much more. Private institutions have used behavioral findings as well. But there is a pervasive and insufficiently explored question: when is it best to ask people to make active choices, and when is it best to use a default rule, which means that people need not make any choice at all? The answer depends on a form of cost–benefit analysis, which means that it is necessary to investigate whether choosing is a burden or a pleasure, whether learning is important, and whether a default rule would satisfy the informed preferences or all of most people.
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How Will We Care for the Mentally Ill?.
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Multimodal Analgesia for Acute Pain.
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Why Sex Education Matters for Adolescents with Autism Spectrum Disorder.
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Canadian Nurses Caught Up in Immigration Policy Confusion.
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Ohio Collaborative Model Proactively Addresses the Looming Nursing Shortage.
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NewsCAP: Diagnostics and treatment options for adult diabetic retinopathy have significantly improved.
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Early Ambulation Is Crucial for Improving Patient Health.
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New Warnings About Protecting Children from Dangerous Substances.
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NewsCAP: In May, the International Council of Nurses awarded the Christiane Reimann Prize to Linda Aiken, PhD, RN, FAAN, FRCN.
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Telemedicine and Telehealth: The Potential to Improve Rural Access to Care.
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New Treatment for Duchenne Muscular Dystrophy.
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New Injectable Drug Treats Moderate-To-Severe Plaque Psoriasis.
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Involvement of hippocampal NMDA receptors in encoding and consolidation, but not retrieval, processes of spontaneous object location memory in rats
Source:Behavioural Brain Research, Volume 331
Author(s): Kazuo Yamada, Misaki Arai, Toshiko Suenaga, Yukio Ichitani
The hippocampus is thought to be involved in object location recognition memory, yet the contribution of hippocampal NMDA receptors to the memory processes, such as encoding, retention and retrieval, is unknown. First, we confirmed that hippocampal infusion of a competitive NMDA receptor antagonist, AP5 (2-amino-5-phosphonopentanoic acid, 20–40nmol), impaired performance of spontaneous object location recognition test but not that of novel object recognition test in Wistar rats. Next, the effects of hippocampal AP5 treatment on each process of object location recognition memory were examined with three different injection times using a 120min delay-interposed test: 15min before the sample phase (Time I), immediately after the sample phase (Time II), and 15min before the test phase (Time III). The blockade of hippocampal NMDA receptors before and immediately after the sample phase, but not before the test phase, markedly impaired performance of object location recognition test, suggesting that hippocampal NMDA receptors play an important role in encoding and consolidation/retention, but not retrieval, of spontaneous object location memory.
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Bombesin administration impairs memory and does not reverse memory deficit caused by sleep deprivation
Source:Behavioural Brain Research, Volume 331
Author(s): L.B.T. Ferreira, S.L.B. Oliveira, J. Raya, L.A. Esumi, D.C. Hipolide
Sleep deprivation impairs performance in emotional memory tasks, however this effect on memory is not completely understood. Possible mechanisms may involve an alteration in neurotransmission systems, as shown by the fact that many drugs that modulate neural pathways can prevent memory impairment by sleep loss. Gastrin releasing peptide (GRP) is a neuropeptide that emerged as a regulatory molecule of emotional memory through the modulation of other neurotransmission systems. Thus, the present study addressed the effect of intraperitoneal (IP) administration of bombesin (BB) (2.5, 5.0 and 10.0μg/kg), a GRP agonist, on the performance of Wistar rats in a multiple trail inhibitory avoidance (MTIA) task, after sleep deprivation, using the modified multiple platforms method (MMPM). Sleep deprived animals exhibited acquisition and retention impairment that was not prevented by BB injection. In addition, non-sleep deprived animals treated with BB before and after the training session, but not before the test, have shown a retention deficit. In summary, BB did not improve the memory impairment by sleep loss and, under normal conditions, produced a memory consolidation deficit.
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Prenatal lipopolysaccharide induces hypothalamic dopaminergic hypoactivity and autistic-like behaviors: Repetitive self-grooming and stereotypies
Source:Behavioural Brain Research, Volume 331
Author(s): Thiago B. Kirsten, Maria M. Bernardi
Previous investigations by our group have shown that prenatal exposure to lipopolysaccharide (LPS), which mimics infection by gram-negative bacteria, induces social, cognitive, and communication deficits. For a complete screening of autistic-like behaviors, the objective of this study was to evaluate if our rat model also induces restricted and repetitive stereotyped behaviors. Thus, we studied the self-grooming microstructure. We also studied the neurochemistry of hypothalamus and frontal cortex, which are brain areas related to autism to better understand central mechanisms involved in our model. Prenatal LPS exposure on gestational day 9.5 increased the head washing episodes (frequency and time), as well as the total self-grooming. However, body grooming, paw/leg licking, tail/genital grooming, and circling behavior/tail chasing did not vary significantly among the groups. Moreover, prenatal LPS induced dopaminergic hypoactivity (HVA metabolite and turnover) in the hypothalamus. Therefore, our rat model induced restricted and repetitive stereotyped behaviors and the other main symptoms of autism experimentally studied in rodent models and also found in patients. The hypothalamic dopaminergic impairments seem to be associated with the autistic-like behaviors.
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Two-hit model of schizophrenia induced by neonatal immune activation and peripubertal stress in rats: Study of sex differences and brain oxidative alterations
Source:Behavioural Brain Research, Volume 331
Author(s): Aline Santos Monte, Bruna Stefânia Ferreira Mello, Vládia Célia Moreira Borella, Tatiane da Silva Araujo, Francisco Eliclécio Rodrigues da Silva, Francisca Cléa F de Sousa, Antônio Carlos Pinheiro de Oliveira, Clarissa Severino Gama, Mary V. Seeman, Silvânia Maria Mendes Vasconcelos, David Freitas De Lucena, Danielle Macêdo
Schizophrenia is considered to be a developmental disorder with distinctive sex differences. Aiming to simulate the vulnerability of the third trimester of human pregnancy to the developmental course of schizophrenia, an animal model was developed, using neonatal poly(I:C) as a first-hit, and peripubertal stress as a second-hit, i.e. a two-hit model. Since, to date, there have been no references to sex differences in the two-hit model, our study sought to determine sex influences on the development of behavior and brain oxidative change in adult rats submitted to neonatal exposure to poly(I:C) on postnatal days 5–7 as well as peripubertal unpredictable stress (PUS). Our results showed that adult two-hit rats present sex-specific behavioral alterations, with females showing more pronounced deficits in prepulse inhibition of the startle reflex and hyperlocomotion, while males showing more deficits in social interaction. Male and female animals exhibited similar working memory deficits. The levels of the endogenous antioxidant, reduced glutathione, were decreased in the prefrontal cortex (PFC) of both male and female animals exposed to both poly(I:C) and poly(I:C)+PUS. Only females presented decrements in GSH levels in the striatum. Nitrite levels were increased in the PFC of male and in the striatum of female poly(I:C)+PUS rats. Increased lipid peroxidation was observed in the PFC of females and in the striatum of males and females exposed to poly(I:C) and poly(I:C)+PUS. Thus, the present study presents evidence for sex differences in behavior and oxidative brain change induced by a two-hit model of schizophrenia.
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Comparing the effect of temporal delay on the availability of egocentric and allocentric information in visual search
Source:Behavioural Brain Research, Volume 331
Author(s): Keira Ball, Yan Birch, Alison Lane, Amanda Ellison, Thomas Schenk
Frames of reference play a central role in perceiving an object's location and reaching to pick that object up. It is thought that the ventral stream, believed to subserve vision for perception, utilises allocentric coding, while the dorsal stream, argued to be responsible for vision for action, primarily uses an egocentric reference frame. We have previously shown that egocentric representations can survive a delay; however, it is possible that in comparison to allocentric information, egocentric information decays more rapidly. Here we directly compare the effect of delay on the availability of egocentric and allocentric representations. We used spatial priming in visual search and repeated the location of the target relative to either a landmark in the search array (allocentric condition) or the observer's body (egocentric condition). Three inter-trial intervals created minimum delays between two consecutive trials of 2, 4, or 8seconds. In both conditions, search times to primed locations were faster than search times to un-primed locations. In the egocentric condition the effects were driven by a reduction in search times when egocentric information was repeated, an effect that was observed at all three delays. In the allocentric condition while search times did not change when the allocentric information was repeated, search times to un-primed target locations became slower. We conclude that egocentric representations are not as transient as previously thought but instead this information is still available, and can influence behaviour, after lengthy periods of delay. We also discuss the possible origins of the differences between allocentric and egocentric priming effects.
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Swimming exercise prevents behavioural disturbances induced by an intracerebroventricular injection of amyloid-β1-42 peptide through modulation of cytokine/NF-kappaB pathway and indoleamine-2,3-dioxygenase in mouse brain
Source:Behavioural Brain Research, Volume 331
Author(s): Leandro Cattelan Souza, Cristiano R. Jesse, Lucian Del Fabbro, Marcelo Gomes de Gomes, André Tiago Rossito Goes, Carlos Borges Filho, Cristiane Luchese, Albanin Aparecida Mielniczki Pereira, Silvana Peterini Boeira
Emerging evidence indicates that the activation of indoleamine-2,3-dioxygenase (IDO), a first and rate-limiting enzyme in the kynurenine (KYN) pathway, is involved in amyloid-beta (Aβ1-42)-neurotoxicity and Alzheimer's disease (AD) pathogenesis. Physical exercise has been considered an effective intervention in AD, attenuating or limiting their progression. Nevertheless, the neurobiological mechanisms underlying the neuroprotective effects of exercise have not yet been fully elucidated. In present study, we investigated the protective effect of an 8-week swimming training (ST) exercise on cognitive and non-cognitive functions and its role in modulating biomarkers of KYN pathway, before an intracerebroventricular (i.c.v.) injection of Aβ1-42 (400pmol/animal; 3μl/site) peptide in mice. Our results demonstrated that ST was effective in preventing the following behavioural disturbances caused by Aβ1-42 injection: memory impairment in the object recognition test and depressive/anxiety-like behaviour in the tail suspension test and elevated plus-maze test, respectively. ST abrogated the neuroinflammatory response and neurotrophic deficiency in the prefrontal cortex and hippocampus induced by Aβ1-42. Also, Aβ1-42 increased IDO activity, KYN and tryptophan (TRP) levels and KYN:TRP ratio in the prefrontal cortex and hippocampus − alterations that were blocked by ST. It can be concluded that ST prevented behavioural and neurobiological deficits induced by Aβ1-42, and suggest that these neuroprotective effects are likely to involve the inhibition of inflammation/IDO activation and up-regulation of neurotrophic factors in brain of mice. Thus, it is possible that physical exercise can be used as a non-pharmacological approach to alleviates both cognitive and non-cognitive symptoms of AD.
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The PTZ kindling mouse model of epilepsy exhibits exploratory drive deficits and aberrant activity amongst VTA dopamine neurons in both familiar and novel space
Source:Behavioural Brain Research, Volume 330
Author(s): Mahboubeh Ahmadi, Jean-Philippe Dufour, Erich Seifritz, Javad Mirnajafi-Zadeh, Bechara J. Saab
Recurrent seizures that define epilepsy are often accompanied by psychosocial problems and cognitive deficits with incompletely understood aetiology. We therefore used the pentylenetetrazol (PTZ) kindling model of epilepsy in mice to examine potential seizure-associated neuropathologies, focusing on motivation, memory and novel-environment-induced activation of midbrain dopaminergic neurons. In addition to recurrent seizures, we found that PTZ kindling led to a strong suppression of novelty-driven exploration while largely sparing fear-driven exploration. The deficits in exploratory drive may be relevant for other cognitive impairments since reduced unassisted rearing in a learning arena correlated with poorer spatial memory of object location. Using c-Fos immunofluorescence as a marker of neuronal activity, we observed that dopamine neurons within the ventral tegmental area (VTA) of PTZ kindled mice demonstrate hyperactivity at baseline and hypoactivity in response to a novel environment compared to saline-injected cagemate controls. These data extend previous findings of PTZ kindling-mediated disruptions of hippocampal processes important for novel environment recognition and learning by demonstrating PTZ kindling also induces motivational deficits that are associated with reduced stimulus-evoked activation of VTA dopamine neurons. More broadly, these data help understand the aetiology of complex behavioural changes in the PTZ kindling model, and may assist in the development of superior diagnoses and treatments for epilepsy.
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Neuroprotective effects of ceftriaxone treatment on cognitive and neuronal deficits in a rat model of accelerated senescence
Source:Behavioural Brain Research, Volume 330
Author(s): Maria A. Tikhonova, Shih-Chun Ho, Anna A. Akopyan, Nataliya G. Kolosova, Jun-Cheng Weng, Wan-Yun Meng, Chih-Li Lin, Tamara G. Amstislavskaya, Ying-Jui Ho
Rats of OXYS strain are characterized by genetically defined accelerated senescence. Ceftriaxone (CEF) exerts neuroprotective effects by decreasing the excitotoxicity and activation of antioxidant system. Here, we studied the effects of CEF (50 or 100mg/kg/day, i.p., 36 days) on cognitive and neuronal deficits in 5-month-old OXYS rats. Chronic CEF administration in a dose of 100mg/kg partially inhibited impairments of movement and restored the deficit in the novel object recognition in OXYS rats. Neuromorphologically, control OXYS rats exhibited a lowered neuronal density in the hippocampal CA1 area and there was a tendency to decrease in the substantia nigra pars compacta compared to Wistar controls. Both doses of CEF increased the density of pyramidal neurons in the CA1 area in OXYS rats. Control OXYS rats demonstrated a tendency to lower tyrosine hydroxylase (TH) immunoreactivity in the striatum compared with Wistar rats, while CEF treatment at a dose of 50mg/kg significantly augmented this parameter. In control OXYS rats, the levels of neurogenesis in the subgranular zone of the dentate gyrus of the hippocampus were significantly higher than in Wistar rats indicating compensatory processes that probably prevented the further induction of neurogenesis by CEF. Restoration of the recognition function and neuronal density in the CA1 area in OXYS rats after CEF treatment might be related to activation of the mechanisms that provide survival of newborn and mature neurons. The data suggested CEF as a promising pharmacological tool for the prevention of cognitive decline at accelerated aging.
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Voluntary wheel running ameliorates depression-like behaviors and brain blood oxygen level-dependent signals in chronic unpredictable mild stress mice
Publication date: 14 July 2017
Source:Behavioural Brain Research, Volume 330
Author(s): Peng Huang, Zhaoyang Dong, Weiliang Huang, Chuying Zhou, Weichao Zhong, Peiqian Hu, Ge Wen, Xuegang Sun, Heyu Hua, Huihui Cao, Lei Gao, Zhiping Lv
BackgroundPhysical exercise has been long recognized for its therapeutic effects on depressive disorders, but the underlying mechanisms remain largely unknown. In the study, we investigated whether the physical exercise by voluntary wheel running (VWR) alters depression-like behaviors and its impact on brain blood oxygen level-dependent (BOLD) signals in mice.MethodsAdult male C57BL/6 mice were assigned to one of the following groups; (1) no exercise control (noEx), housed in a standard cage; (2) exercise (Ex), 2h/day in a running wheel apparatus; (3) chronic unpredictable mild stress (CUMS), which was imitating adult stress; and (4) CUMS+Ex. The differences in functional brain changes were determined by BOLD functional magnetic resonance imaging (fMRI).ResultsThe results showed that VWR exercise significantly reversed the CUMS-induced behavioral abnormalities. Base on the fMRI amplitude of low-frequency fluctuation (ALFF) analysis, we found that VWR exercise could restore the CUMS-induced excessive BOLD activation in parts of limbic system, such as cortex, hippocampus and corpus callosum. Furthermore, CUMS-induced BOLD suppressive regions were also partially attenuated by VWR exercise, such as amygdala, cerebellum anterior lobe, thalamus, midbrain, and pontine. Most of these regions are involved in mood-regulating circuit, suggesting dysfunction of the circuit in CUMS model of depression, and VWR exercise could adjust the mood-regulating circuit.ConclusionsThese results suggested that VWR exercise ameliorated depression-like behaviors and brain BOLD signals in CUMS induced depression mice.
Graphical abstract
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Acute low-level alcohol consumption reduces phase locking of event-related oscillations in rodents
Source:Behavioural Brain Research, Volume 330
Author(s): Leslie R. Amodeo, Derek N. Wills, Cindy L. Ehlers
Event-related oscillations (EROs) are rhythmic changes that are evoked by a sensory and/or cognitive stimulus that can influence the dynamics of the EEG. EROs are defined by the decomposition of the EEG signal into magnitude (energy) and phase information and can be elicited in both humans and animals. EROs have been linked to several relevant genes associated with ethanol dependence phenotypes in humans and are altered in selectively bred alcohol-preferring rats. However, pharmacological studies are only beginning to emerge investigating the impact low intoxicating doses of ethanol can have on event-related neural oscillations. The main goal of this study was to investigate the effects of low levels of voluntary consumption of ethanol, in rats, on phase locking of EROs in order to give further insight into the acute intoxicating effects of ethanol on the brain. To this end, we allow rats to self-administer unsweetened 20% ethanol over 15 intermittent sessions. This method results in a stable low-dose consumption of ethanol. Using an auditory event-related potential "oddball" paradigm, we investigated the effects of alcohol on the phase variability of EROs from electrodes implanted into the frontal cortex, dorsal hippocampus, and amygdala. We found that intermittent ethanol self-administration was sufficient to produce a significant reduction in overall intraregional synchrony across all targeted regions. These data suggest that phase locking of EROs within brain regions known to be impacted by alcohol may represent a sensitive biomarker of low levels of alcohol intoxication.
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A new method for the localization of the innervation zone based on monopolar surface-detected potentials
Publication date: Available online 25 May 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Javier Rodriguez-Falces
In monopolar electrode configuration, the shape of the motor unit potential (MUP) undergoes essential morphologic changes with increasing distance from the innervation zone. In particular, the rising phase of the MUP slows down and becomes longer as the electrode is moved further from the innervation zone. Based on this, it is hypothesized that the maximum slope of the rising phase of a monopolar MUP (SlopeMAX) would reach its highest value at the innervation zone. Herein, we sought to determine whether the location of the innervation zone coincides with the position in the muscle of the monopolar MUP with highest SlopeMAX and whether new criteria for the localization of the innervation region can be proposed based on the SlopeMAX of monopolar potentials. Multichannel surface (13×5 electrode array) and intramuscular (wire electrodes inserted with needles of lengths 15 and 25 mm) EMG signals were concurrently recorded in monopolar configuration from the biceps brachii muscle of 10 healthy subjects. The spatial distribution of monopolar and bipolar MUPs along the fibers' direction were obtained by spike-triggered averaging of the surface EMG. We found that the monopolar MUP with steepest rising phase (i.e., highest SlopeMAX) was located either just above or at half of the inter-electrode distance from the innervation zone. High levels of agreement (94-98%) were found between the position of the innervation zone assessed with the SlopeMAX criteria of monopolar potentials and the position identified using the phase reversal criteria of bipolar potentials. The present results legitimize the use of compound muscle action potentials (M waves) to localize the innervation zone: this location would correspond to the electrode position which yielded the monopolar M wave with highest SlopeMAX.
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Editorial Board and Contents
Publication date: June 2017
Source:Trends in Immunology, Volume 38, Issue 6
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Lipopolysaccharide Detection across the Kingdoms of Life
Publication date: Available online 24 May 2017
Source:Trends in Immunology
Author(s): Jonathan C. Kagan
Studies in recent years have uncovered a diverse set of eukaryotic receptors that recognize lipopolysaccharide (LPS), the major outer-membrane component of Gram-negative bacteria. Indeed, Toll-like receptors, G-protein-coupled receptors, integrins, receptor-like kinases, and caspases have emerged as important LPS-interacting proteins. In this review, the mammalian receptors that detect LPS are described. I highlight how no host protein is involved in all LPS responses, but a single lipid (phosphatidylinositol-4,5-bisphosphate) regulates many LPS responses, including endocytosis, phagocytosis, inflammation, and pyroptosis. I further describe LPS response systems that operate specifically in plants, and discuss potentially new LPS response systems that await discovery. This diversity of receptors for a single microbial product underscores the importance of host–microbe interactions in multiple kingdoms of life.
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Bilateral Optic Disc Pits With Posterior Pituitary Ectopia.
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Author’s Reply: A Systematic Review of Complications Associated with Direct Implants vs. Tissue Expanders Following Wise Pattern Skin-Sparing Mastectomy
We would like to thank the authors who read with and subsequently provided a reply to our original article entitled: "A Systematic Review of Complications Associated with Direct Implants vs. Tissue Expanders Following Wise Pattern Skin-Sparing Mastectomy."1,2 Firstly, regarding our methodology, the author's put forth the notion that numbers 20 and 21 of the PRISMA guidelines were not followed correctly, as we did not provide confidence intervals or I2 values for the included studies. According to an erratum published on the PRISMA website (http://ift.tt/2rVS4D4), "The published PRISMA checklists contain an error in the wording for Item 21.
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Revisiting the value of competition assays in folate receptor-mediated drug delivery
Publication date: September 2017
Source:Biomaterials, Volume 138
Author(s): Steven K. Jones, Anwesha Sarkar, Daniel P. Feldmann, Peter Hoffmann, Olivia M. Merkel
Polymeric nanoparticles have been studied for gene and drug delivery. These nanoparticles can be modified to utilize a targeted delivery approach to selectively deliver their payload to specific cells, while avoiding unwanted delivery to healthy cells. One commonly over-expressed receptor which can be targeted by ligand-conjugated nanoparticles is the folate receptor alpha (FRα). The ability to target FRα remains a promising concept, and therefore, understanding the binding dynamics of the receptor with the ligand of the nanoparticle therapeutic can provide valuable insight. This manuscript focuses on the interaction between self-assembled nanoparticles decorated with a folic acid (FA) ligand and FRα. The nanoparticles consist of micelles formed with a FA conjugated triblock copolymer (PEI-g-PCL-b-PEG-FA) which condensed siRNA to form micelleplexes. By combining biological and biophysical approaches, this manuscript explores the binding kinetics and force of the targeted siRNA containing nanoparticles to FRα in comparison with free FA. We demonstrate via flow cytometry and atomic force microscopy that multivalent micelleplexes bind to FRα with a higher binding probability and binding force than monovalent FA. Furthermore, we revisited why competitive inhibition studies of binding of multivalent nanoparticles to their respective receptor are often reported in literature to be inconclusive evidence of effective receptor targeting. In conclusion, the results presented in this paper suggest that multivalent targeted nanoparticles display strong receptor binding that a monovalent ligand may not be able to compete with under in vitro conditions and that high concentrations of competing monovalent ligands can lead to measurement artifacts.
Graphical abstract
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Catalase-loaded cisplatin-prodrug-constructed liposomes to overcome tumor hypoxia for enhanced chemo-radiotherapy of cancer
Source:Biomaterials, Volume 138
Author(s): Rui Zhang, Xuejiao Song, Chao Liang, Xuan Yi, Guosheng Song, Yu Chao, Yu Yang, Kai Yang, Liangzhu Feng, Zhuang Liu
Aiming at improved therapeutic efficacies, the combination of chemotherapy and radiotherapy (chemo-radiotherapy) has been widely studied and applied in clinic. However, the hostile characteristics of tumor microenvironment such as hypoxia often limit the efficacies in both types of cancer therapies. Herein, catalase (CAT), an antioxidant enzyme, is encapsulated inside liposomes constituted by cisplatin (IV)-prodrug-conjugated phospholipid, forming CAT@Pt (IV)-liposome for enhanced chemo-radiotherapy of cancer. After being loaded inside liposomes, CAT within CAT@Pt (IV)-liposome shows retained and well-protected enzyme activity, and is able to trigger decomposition of H2O2 produced by tumor cells, so as to produce additional oxygen for hypoxia relief. As the result, treatment of CAT@Pt (IV)-liposome induces the highest level of DNA damage in cancer cells after X-ray radiation compared to the control groups. In vivo tumor treatment further demonstrates a remarkably improved therapeutic outcome in chemo-radiotherapy with such CAT@Pt (IV)-liposome nanoparticles. Hence, an exquisite type of liposome-based nanoparticles is developed in this work by integrating cisplatin-based chemotherapy and catalase-induced tumor hypoxia relief together for combined chemo-radiotherapy with great synergistic efficacy, promising for clinical translation in cancer treatment.
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Linear polysialoside outperforms dendritic analogs for inhibition of influenza virus infection in vitro and in vivo
Publication date: September 2017
Source:Biomaterials, Volume 138
Author(s): Sumati Bhatia, Daniel Lauster, Markus Bardua, Kai Ludwig, Stefano Angioletti-Uberti, Nicole Popp, Ute Hoffmann, Florian Paulus, Matthias Budt, Marlena Stadtmüller, Thorsten Wolff, Alf Hamann, Christoph Böttcher, Andreas Herrmann, Rainer Haag
Inhibition of influenza A virus infection by multivalent sialic acid inhibitors preventing viral hemagglutinin binding to host cells of the respiratory tract is a promising strategy. However, optimal geometry and optimal ligand presentation on multivalent scaffolds for efficient inhibition both in vitro and in vivo application are still unclear. Here, by comparing linear and dendritic polyglycerol sialosides (LPGSA and dPGSA) we identified architectural requirements and optimal ligand densities for an efficient multivalent inhibitor of influenza virus A/X31/1 (H3N2). Due to its large volume, the LPGSA at optimal ligand density sterically shielded the virus significantly better than the dendritic analog. A statistical mechanics model rationalizes the relevance of ligand density, morphology, and the size of multivalent scaffolds for the potential to inhibit virus-cell binding. Optimized LPGSA inhibited virus infection at IC50 in the low nanomolar nanoparticle concentration range and also showed potent antiviral activity against two avian influenza strains A/Mallard/439/2004 (H3N2) and A/turkey/Italy/472/1999 (H7N1) post infection. In vivo application of inhibitors clearly confirmed the higher inhibition potential of linear multivalent scaffolds to prevent infection. The optimized LPGSA did not show any acute toxicity, and was much more potent than the neuraminidase inhibitor oseltamivir carboxylate in vivo. Combined application of the LPGSA and oseltamivir carboxylate revealed a synergistic inhibitory effect and successfully prevented influenza virus infection in mice.
Graphical abstract
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Intracellular delivery of oligonucleotides in Helicobacter pylori by fusogenic liposomes in the presence of gastric mucus
Source:Biomaterials, Volume 138
Author(s): Rita S. Santos, George R. Dakwar, Elisa Zagato, Toon Brans, Céu Figueiredo, Koen Raemdonck, Nuno F. Azevedo, Stefaan C. De Smedt, Kevin Braeckmans
The rising antimicrobial resistance contributes to 25000 annual deaths in Europe. This threat to the public health can only be tackled if novel antimicrobials are developed, combined with a more precise use of the currently available antibiotics through the implementation of fast, specific, diagnostic methods. Nucleic acid mimics (NAMs) that are able to hybridize intracellular bacterial RNA have the potential to become such a new class of antimicrobials and additionally could serve as specific detection probes. However, an essential requirement is that these NAMs should be delivered into the bacterial cytoplasm, which is a particular challenge given the fact that they are charged macromolecules.We consider these delivery challenges in relation to the gastric pathogen Helicobacter pylori, the most frequent chronic infection worldwide. In particular, we evaluate if cationic fusogenic liposomes are suitable carriers to deliver NAMs across the gastric mucus barrier and the bacterial envelope. Our study shows that DOTAP-DOPE liposomes post-PEGylated with DSPE-PEG (DSPE Lpx) can indeed successfully deliver NAMs into Helicobacter pylori, while offering protection to the NAMs from binding and inactivation in gastric mucus isolated from pigs. DSPE Lpx thus offer exciting new possibilities for in vivo diagnosis and treatment of Helicobacter pylori infections.
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Nutrition Across the Lifespan for Healthy Aging: Proceedings of a Workshop.
In September 2016, the National Academies of Sciences, Engineering, and Medicine convened a workshop to examine trends and patterns in aging and factors related to healthy aging in the United States, with a focus on nutrition, and how nutrition can sustain and promote healthy aging, not just in late adulthood, but beginning in pregnancy and early childhood and extending throughout the lifespan. Participants discussed the role of nutrition in the aging process at various stages in life, changes in organ systems over the lifespan and changes that occur with age related to cognitive, brain, and mental health, and explored opportunities to move forward in promoting healthy aging in the United States. This publication summarizes the presentations and discussions from the workshop.
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First Aid Training May Improve First Aid Skills [Internet].
Each year approximately half a million people in Norway suffer injury caused by accidents, violence or self inflicted injury and about 3,000 experience out of hospital cardiac arrest. Surveys have indicated that many Norwegians have limited first aid skills. The Norwegian Ministry of Health and Care Services have commissioned an overview of the effect of first aid training.
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Efficacy and Cost-Effectiveness of Alendronate for the Prevention of Fractures in Postmenopausal Women in Norway [Internet].
Background: The Norwegian guidelines for prevention and treatment of osteoporosis and osteoporosis-related fractures recommend treatment with bisphosphonates for women with T-score less than -1.6 and previous fractures and also for women with T-score less than or equal to -2.5 without previous fracture. Only women with T-score equal to or less than -2.5 who have previous fractures will have their drug expenses reimbursed.
http://ift.tt/2qUlfrM
Evaluation of 32 Priority Guidelines – a System-Wide Intervention on Waiting Time Reduction for Elective Treatment in the Norwegian Specialist Health Service [Internet].
Different measures to reduce waiting time for elective treatment in the Norwegian specialist health service have been in place. In the period from 2008 to 2010 the Norwegian directorate for health introduced 32 priority guidelines to give guided priority to either an outpatient consultation or treatment for 398 conditions, and a specified maximum waiting time. The priority guidelines were developed by 32 national grops of experts under the supervision of the Norwegian Directorate for Health.
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Autologous Hematopoietic Stemcell Transplantation for Multiple Sclerosis [Internet].
Autologous hematopoietic stem cell transplantation is a treatment that has been suggested for a small group of patients with relapsing remitting multiple sclerosis where available medication has limited effect or causes serious side effects. In this Health Technology Assessment we have summarized and evaluated research of efficacy, safety, economic evaluations and ethical considerations related to autologous stem cell transplantation for multiple sclerosis. We did not identify any controlled study, with the exception of one very small randomized controlled trial with limited relevance. The other studies were one registry study and 21 smaller case series, of which eight mainly comprised relapsing-remitting multiple sclerosis. We assessed the quality of the evidence as low for mortality at 100 days, and very low for all other outcomes. There is considerable uncertainty linked to the results. We found that:
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Treatment of Persons who Suffer from Both an Eating Disorder and Diabetes [Internet].
This systematic review addresses treatment of persons who suffer from both an eating disorder and diabetes. Relevant interventions include structured treatment with a focus on control of blood sugar and regular meals, and/or in combination with psychological treatment.
http://ift.tt/2qphSFA
Evidence Summaries: New Medicines – Integrated Process Statement [Internet].
This integrated process statement has been produced to explain how 'Evidence summaries: new medicines' (ESNMs) are developed. It provides an overview of the key process principles and describes all stages of the development of ESNMs. These procedures are designed to ensure that a robust, quality-assured, commentary is developed for the NHS in an open, transparent and timely way, with appropriate input from key groups.
http://ift.tt/2qUlenI
A Health Technology Assessment of the New Drugs for Inoperable or Metastatic Malignant Melanoma Patients [Internet].
In this health technology assessment we have compared the relative effectiveness and cost-effectiveness of seven new drugs used for the treatment of advanced malignant melanoma patients in the Norwegian setting. The drugs are: cobimetinib, dabrafenib, ipilimumab, nivolumab, pembrolizumab, trametinib and vemurafenib.
http://ift.tt/2qp4Rfr
RGO/Au NPs/N-doped CNTs supported on nickel foam as an anode for enzymatic biofuel cells
Publication date: 15 November 2017
Source:Biosensors and Bioelectronics, Volume 97
Author(s): He Zhang, Lingling Zhang, Yujie Han, You Yu, Miao Xu, Xueping Zhang, Liang Huang, Shaojun Dong
In this study, three-dimensional reduced graphene oxide/Au NPs/nitrogen-doped carbon nanotubes (RGO/Au NPs/N-doped CNTs) assembly supported on nickel foam was utilized as an anode for enzymatic biofuel cells (EBFCs). 3D RGO/Au NPs was obtained by electrodepositing reduced graphene oxide on nickel foam (Ni foam), while Au NPs were co-deposited during the process. Afterwards, nitrogen doped CNTs (N-CNTs) were allowed to grow seamlessly on the surfaces of 3D RGO/Au NPs via a simple chemical vapor deposition (CVD) process. In this nanostructure, Au NPs co-deposition and nitrogen doping offer more active sites for bioelectrocatalysis. Additionally, N-CNTs were demonstrated providing high specific surface area for enzyme immobilization and facilitating the electron transfer between glucose oxidase (GOx) and electrode. The resulting bioanode achieved efficient glucose oxidation with high current densities of 7.02mAcm−2 (0.3V vs. Ag/AgCl). Coupling with a Pt cathode, the fabricated glucose/air biofuel cell exhibited an open-circuit potential of 0.32V and generated a maximum power density 235µWcm−2 at 0.15V. This novel electrode substrate achieved high performance in current density at bioelectrochemical systems and could be useful for further exploiting the application of three dimensional carbon-based nanomaterials in EBFCs.
Graphical abstract
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Clinical Features and Treatment of Dermatofibrosarcoma Protuberans Affecting the Vulva: A Literature Review
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Safety of Cochlear Implants in Electrosurgery: A Systematic Review of the Literature
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Novel Approach to Treating Androgenetic Alopecia in Females With Photobiomodulation (Low-Level Laser Therapy)
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Comparison of the American Joint Committee on Cancer Seventh Edition and Brigham and Women's Hospital Cutaneous Squamous Cell Carcinoma Tumor Staging in Immunosuppressed Patients
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Locally Recurrent Lentigo Maligna and Lentigo Maligna Melanoma: Characteristics and Time to Recurrence After Surgery
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Frequency of Subungual Melanoma in Longitudinal Melanonychia: A Single-Center Experience
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Tumor Margin Assessment With Loupe Magnification Enables Greater Histological Clearance of Facial Basal Cell Carcinomas Compared With Clinical Examination Alone
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Scrotal Melanoma: A Systematic Review of Presentation, Treatment, and Outcomes
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Solitary Large Keratoacanthomas of the Head and Neck: An Observational Study
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Color Doppler Ultrasound Assessment of Activity in Keloids
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Autologous Pure Platelet-Rich Plasma Dermal Injections for Facial Skin Rejuvenation: Clinical, Instrumental, and Flow Cytometry Assessment
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New Classification System for Tear Trough Deformity
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The protective effect of quercetin on cyclophosphamide-Induced lung toxicity in rats
Publication date: August 2017
Source:Biomedicine & Pharmacotherapy, Volume 92
Author(s): Emin Şengül, Volkan Gelen, Semin Gedikli, Seçkin Özkanlar, Cihan Gür, Fikret Çelebi, Ali Çınar
Cyclophosphamide (CYP) is an anticancer agent widely used in chemotherapy. It has been suggested that CYP causes toxicity in many organs, including the lungs and testes. Many studies have indicated that some antioxidants have possible protective effects against CYP's side effects. This study aimed to investigate the protective effect of quercetin (QUE) on CYP-induced lung toxicity in rats using histologic and biochemical methods.In the study, 50 male Sprague-Dawley rats weighing 220–250g were used. There were 4 experimental groups and 1 control group. Group I is the control group, which was given only intragastric (i.g.) solvent (corn oil) for 7days. Group II was given i.g. corn oil for 7days as a placebo, and a single dose of intraperitoneal (i.p.) CYP (200mg/kg) was given on day 7. Groups III and IV, respectively, were given QUE in doses of 50 and 100mg/kg, dissolved in corn oil, and administered i.g. for 7days. In addition, a single dose of CYP (200mg/kg, i.p.) was administered on the 7th day of study. In Group V, a 100mg/kg dose of QUE was given to rats i.g. for 7days. On the 8th day of the experiment, all groups of rats' blood and lung tissue samples were collected for analysis of oxidative stress parameters and histopathological examinations.In the biochemical result (although oxidative parameters were increased in favor of tissue damage) QUE administration revealed attenuated CYP toxicity in the rats 'lungs. In histologic analysis, QUE prevented the CYP-mediated tissue damage and the increase in mast-cell densities in the rats' lung tissues.The results of the present study have revealed that QUE provides a possible protective effect by inhibiting ROS and mast cell degranulation in induced lung damage.
Graphical abstract
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Justicia spicigera Schltdl. and kaempferitrin as potential anticonvulsant natural products
Publication date: August 2017
Source:Biomedicine & Pharmacotherapy, Volume 92
Author(s): Ma. Eva González-Trujano, Fabiola Domínguez, Gimena Pérez-Ortega, Miguel Aguillón, David Martínez-Vargas, Salvador Almazán-Alvarado, Adrián Martínez
Justicia spicigera Schltdl. is a vegetal species traditionally used to control epilepsy, but scientific evidence is required to reinforce this activity. The aim of the study was to evaluate the anticonvulsant-like activity of J. spicigera aqueous extract (JsAE) and a bioactive compound. JsAE was assessed in a dose-response manner (30, 100 and 1000mg/kg, i.p.) using the pentylenetetrazol (PTZ)-induced seizures and maximal electroshock seizure (MES) test in mice in comparison to ethosuximide (ETX, reference drug 100mg/kg, i.p.) or phenytoin (25mg/kg, i.p.), respectively. Then a significant dosage (1000mg/kg, i.p.) was chosen to examine electrographic activity (EEG) in rats. Treatment groups were compared to the vehicle and ETX in the convulsive behavior alone or simultaneous to EEG after PTZ-induced seizures (80 or 35mg/kg, i.p., mice or rats). Kaempferitrin (a flavonoid of JsAE) and ETX were administered via intracerebroventricular (i.c.v, 4th ventricle, 1μg/μL) and tested in the presence of PTZ in rats. Results confirmed that JsAE delayed the onset of seizures and reduced frequency of tonic convulsion and mortality in mice. JsAE or kaempferitrin also decreased the EEG spikes frequency and amplitude in a similar manner than EXT in rats. In conclusion, these preliminary data give evidence of the potential of J. spicigera as possible anticonvulsant as recommended in folk medicine for treating epilepsy, where kaempferitrin is suggested as a partial responsible bioactive compound.
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Cytotoxicity of temozolomide on human glioblastoma cells is enhanced by the concomitant exposure to an extremely low-frequency electromagnetic field (100Hz, 100G)
Publication date: August 2017
Source:Biomedicine & Pharmacotherapy, Volume 92
Author(s): Zeinab Akbarnejad, Hossein Eskandary, Luciana Dini, Cristian Vergallo, Seyed Noureddin Nematollahi-Mahani, Alireza Farsinejad, Maryam Fekri Soofi Abadi, Meysam Ahmadi
Glioblastoma multiforme (GBM) is the most malignant brain cancer that causes high mortality in humans. It responds poorly to the most common cancer treatments, such as surgery, chemo- and radiation therapy. Temozolomide (TMZ) is an alkylating agent that has been widely used to treat GBM; resistance to this drug is often found. One unexplored possibility for overcoming this resistance is a treatment based on concomitant exposure to electromagnetic fields (EMF) and TMZ. Indeed, many evidences show that EMF affects cancer cells and drug performance. In this study, we evaluated the potential synergistic effect of 100μM TMZ and EMF (100Hz, 100G) on two human glioma cells line, i.e., U87 and T98G above single treatments, TMZ or EMF. Co-treatment synergistically enhanced apoptosis in U87 and T98G cells, by increasing the expression of P53, Bax, and Caspase-3 and decreasing that of Bcl-2 and Cyclin-D1. We also observed an increase in reactive oxygen species (ROS) production and the overexpression of the heme oxygenase-1 (HO-1) gene in comparison to controls. In conclusion, since EMF enhanced the apoptotic effect of TMZ, possibly through a redox regulation mechanism, the TMZ/EMF combination may be effective for glioma cancer treating. Further studies are needed to reveal the action mechanism of this possible novel therapeutic approach.
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Molecular assessment of protective effect of Vitex negundo in ISO induced myocardial infarction in rats
Publication date: August 2017
Source:Biomedicine & Pharmacotherapy, Volume 92
Author(s): Maruthi Prasad E., Ramgopal Mopuri, Madhusudana Pulaganti, Mohammed Abdul Kareem, Md. Shahidul Islam, Dase Gowda K.R, Mackraj Irene, Yingli Lu, Lakshmi Devi Kodidhela
Myocardial infarction (MI) is the one of the major causes of death worldwide, however the molecular mechanisms hidden under this disease conditions remain unknown. This demands serious attention to unravel the molecular mechanisms to identify the therapeutic strategies either to prevent or to control MI. Ayurveda is becoming one of the best alternatives for the modern medicines. On the other hand, Vitex negundo is one of the medicinally important plants used for various diseases and to date, its cardioprotective role is not fully elucidated. In the present study, we made an attempt to understand the cardiac signaling cascade of Akt1 and NF-κB in isoproterenol (ISO)-induced MI, and targeting these signaling molecules by using V. negundo leaf ethanolic extract (VNE). Our findings demonstrate that VNE significantly protects the ISO-induced MI by regulating NF-κB and Akt1experssion in rats.
Graphical abstract
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Omentin-1 prevents cartilage matrix destruction by regulating matrix metalloproteinases
Publication date: August 2017
Source:Biomedicine & Pharmacotherapy, Volume 92
Author(s): Zhigang Li, Baoyi Liu, Dewei Zhao, BenJie Wang, Yupeng Liu, Yao Zhang, Borui Li, Fengde Tian
Matrix metalloproteinases (MMPs) play a crucial role in the degradation of the extracellular matrix and pathological progression of osteoarthritis (OA). Omentin-1 is a newly identified anti-inflammatory adipokine. Little information regarding the protective effects of omentin-1 in OA has been reported before. In the current study, our results indicated that omentin-1 suppressed expression of MMP-1, MMP-3, and MMP-13 induced by the proinflammatory cytokine interleukin-1β (IL-1β) at both the mRNA and protein levels in human chondrocytes. Importantly, administration of omentin-1 abolished IL-1β-induced degradation of type II collagen (Col II) and aggrecan, the two major extracellular matrix components in articular cartilage, in a dose-dependent manner. Mechanistically, omentin-1 ameliorated the expression of interferon regulatory factor 1 (IRF-1) by blocking the JAK-2/STAT3 pathway. Our results indicate that omentin-1 may have a potential chondroprotective therapeutic capacity.
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Barriers and Attitudes to Research Among Residents in Plastic and Reconstructive Surgery: A National Multicenter Cross-Sectional Study
Publication date: Available online 24 May 2017
Source:Journal of Surgical Education
Author(s): The Canadian Plastic Surgery Research, Sarah Al Youha, Becher Alhalabi, Jill Stone, Helene Retrouvey, Osama Samargandi, Johnny Ionut Efanov, Michael Stein, Alexander Morzycki, Haley Augustine, Emilie Bougie, Diana Song, Hollie Power, Julian Diaz-Abele, Caitlin Symonette, Marie Noland, Chris Coroneos, Sophocles Voineskos, Joshua Vorstenbosch, Toni Zhong, Michael Bezuhly, Jason G. Williams
ObjectiveResearch sets the foundation for developing plastic surgeons who think critically and approach clinical practice with an inquisitive mind. The objective of this study was to characterize current attitudes and perceived barriers towards conducting research during residency.DesignA validated 36-item questionnaire was developed by a national task-force of Canadian plastic surgery trainees. The survey was distributed to all 13 plastic surgery programs in Canada. Data was collected for a period of 2 months in the form of multiple choice, Likert scales and short answers.ResultsThe response rate was 64% (95/149) with representation from all 13 plastic surgery programs across Canada. The top three perceived barriers to conducting research were lack of time (83%), insufficient access to research supervisors and mentors (42%) and the research ethics process (38%). More than 70% of residents were interested in conducting research during residency and 74% of programs have a research requirement integrated into their curriculum. Despite this, less than half of residents (47%) believed that their program fosters a culture that promotes research. This was attributed to multiple factors, including a lack of internal research funding (78%), limited access to a research methods or clinical trials unit (78%), and insufficient research training (68%). University research ranking had no correlation with residents' scholarly output or their perceptions towards research barriers.ConclusionCanadian Plastic Surgery residents identified several important factors considered to be barriers to research. Programs can use these findings to address barriers and improve the integration of research throughout residency training.
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Determining the Effect of External Stressors on Laparoscopic Skills and Performance Between Obstetrics and Gynecology Residents
Publication date: Available online 25 May 2017
Source:Journal of Surgical Education
Author(s): Gaby N. Moawad, Paul Tyan, Dipti Kumar, Jill Krapf, Cherie Marfori, Elias D. Abi Khalil, James Robinson
Study ObjectiveTo evaluate the effect of stress on laparoscopic skills between obstetrics and gynecology residents.DesignObservational prospective cohort study.Design ClassificationProspective cohort.SettingUrban teaching university hospital.Participants (Patients)Thirty-one obstetrics and gynecology residents, postgraduate years 1 to 4.InterventionWe assessed 4 basic laparoscopic skills at 2 sessions. The first session was the baseline; 6 months later the same skills were assessed under audiovisual stressors. We compared the effect of stress on accuracy and efficiency between the 2 sessions.Measurements and Main ResultsA linear model was used to analyze time. Under stress, residents were more efficient in 3 of the 4 modules. Ring transfer (hand-eye coordination and bimanual dexterity), p = 0.0304. Ring of fire (bimanual dexterity and measure of depth perception), p = 0.0024 and dissection glove (respect of delicate tissue planes), p = 0.0002. Poisson regression was used to analyze the total number of penalties. Residents were more likely to acquire penalties under stress. Ring transfer, p = 0.0184 and cobra (hand-to-hand coordination), p = 0.0487 yielded a statistically significant increase in penalties in the presence of stressors. Dissection glove p = 0.0605 yielded a nonsignificant increase in penalties.ConclusionOur work confirmed that while under stress residents were more efficient, this translated into their ability to complete tasks faster in all the tested skills. Efficiency, however, came at the expense of accuracy.
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Verification of brain ring enhancing lesions by advanced MR techniques
Publication date: Available online 25 May 2017
Source:Alexandria Journal of Medicine
Author(s): Momena Essam Elsadway, Heba Ibrahim Ali
PurposeTo evaluate the role of MR Spectroscopy in verification and differentiation of different brain ring enhancing lesions, for better diagnostic purpose and management outcome.Patients and methods25 patients were included in this study, 15 of them were males and 10 were females, with age ranging between 21 and 75 (mean 46±14). All patients were presented with variable symptoms, some of them have known primary disease entity and others presented with headache, visual disorders or disturbed level of consciousness. MRI was done to all the patients including conventional and contrast sequences, as well as MR Spectroscopy. Some did MR perfusion and DTI in order to further characterize their nature.Histopathological findings and results of clinical follow up were our reference standard.ResultsAmong the 25 patients, MR Spectroscopy was able to specify 22 lesions (88%), DTI was performed in 13 out of 25 lesions and MR perfusion was performed in 8 out of 25 lesions.ConclusionsCharacterization of ring enhancing lesions of the brain has increased accuracy by applying advanced MRI techniques. In this study, MR Spectroscopy combined with DTI and MR perfusion sequences in some cases improved verification of different ring enhancing brain lesions.
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Prevalence of Exercise Addiction Symptomology and Disordered Eating in Australian Students Studying Nutrition and Dietetics
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Tetyana Rocks, Fiona Pelly, Gary Slater, Lisa Anne Martin
BackgroundPrevious research has reported the existence of disordered eating in students studying nutrition and dietetics. However, the occurrence of exercise addiction, previously linked to disordered eating, is poorly understood in this group.ObjectiveThe main objective of this study was to explore the prevalence of self-reported symptoms of exercise addiction and the association with disordered eating in a sample of students studying nutrition and dietetics. A secondary objective was to compare the prevalence of exercise addiction to students enrolled in another health-related degree.DesignWe conducted a cross-sectional study in 165 undergraduate students.Participants/settingParticipants were students of both sexes enrolled in nutrition and dietetics and occupational therapy degree programs at an Australian university in August 2013.Main outcome measuresParticipants completed four validated questionnaires for assessment of exercise- and eating-related attitudes and behaviors measuring scores for exercise addiction, weekly volume of physical activity (PA), eating disorder symptoms, and cognitive restraint. Stretch stature and body mass were measured and body composition was assessed using dual energy x-ray absorptiometry.Statistical analyses performedIndependent t test, Mann-Whitney U test, and χ2 test were completed to compare groups of students based on sex, degree, or eating attitudes. Spearman's correlation was performed to explore associations between continuous variables (exercise addiction scores, PA volume, and scores for eating attitudes and cognitive restraint).ResultsApproximately 23% of nutrition and dietetics students were found to be at risk of exercise addiction (20% females and 35% males; P=0.205), while the majority demonstrated some symptoms of exercise addiction. A similar proportion of at risk individuals was found in the female occupational therapy group (19%; P=1.000). In females (nutrition and dietetics and occupational therapy combined), the exercise addiction scores were associated with three other outcome measures: PA volume (rs=0.41; P<0.001), eating attitudes scores (rs=0.24; P=0.008), and cognitive restraint (rs=0.32; P<0.001). Comparative analysis indicated that female students with high cognitive restraint had greater exercise addiction scores than those with low cognitive restraint (20.3 [4.8] compared to 17.8 [4.2]; P=0.003).ConclusionsResults suggest high prevalence of exercise addiction in this sample of undergraduate health-related degree students and its link to amount of PA and disordered eating in females. Future research should include larger samples of both sexes to build the existing understanding on these maladaptive behaviors.
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The essential oil from the twigs of Cinnamomum cassia Presl inhibits oxytocin-induced uterine contraction in vitro and in vivo
Publication date: 12 July 2017
Source:Journal of Ethnopharmacology, Volume 206
Author(s): Lan Sun, Li-Na Liu, Jia-Chun Li, Yao-Zhong Lv, Shao-Bo Zong, Jun Zhou, Zheng-Zhong Wang, Jun-Ping Kou, Wei Xiao
Ethnopharmacological relevanceThe twigs and bark of Cinnamomum cassia Presl (Lauraceae) are widely used in traditional Chinese medicine in the treatment of tumor, abdominal pain, dysmenorrhea, digestive system disease and inflammatory diseases. The aim of this study was to determine the inhibitory effect of the essential oil from the twigs of Cinnamomum cassia Presl (EOCC) on uterine contraction in vitro and in vivo.Materials and methodsThe Institute of Cancer Research (ICR) mouse uterine contraction was induced by oxytocin (OT) exposure following estradiol benzoate pretreatment. Mice were given the EOCC (60, 30, and 15mg/kg) by gavage. The level of prostaglandin F2α (PGF2α) in uterine tissue were determined according to specification of enzyme linked immunosorbent assay (ELISA) kit. Uterine tissue was collected for histopathological analysis (H&E). Myosin light chain 20 (MLC20), phosphorylation of myosin light chain 20 (p-MLC20) and cyclooxygenase-2 (COX-2) proteins in uterine tissue were assessed by Western Blot. Mouse isolated uterus strips were mounted in tissue organ baths containing Locke's solution. The contractile responses were recorded with Power Lab recording system. The effect of the EOCC on uterine contraction induced by OT, PGF2α, and acetylcholine (Ach) was observed. Myometrial cells were exposed to OT (7μM) to induce Ca2+ release, and the effect of the EOCC (100, 50, and 25μg/ml) on intracellular Ca2+ was analysed with fluorometry imaging.ResultsIn vivo study demonstrated that the EOCC significantly reduced OT-induced writhing responses with a maximal inhibition of 66.5%. It also decreased the level of PGF2α in OT-induced mice uterine tissue. Moreover, Western blot analysis showed that COX-2 and p-MLC20 expressions in uterine tissue of dysmenorrhea mice were significantly reduced. EOCC inhibited spontaneous uterus contractions in a dose-dependent manner, and the concentration of the EOCC giving 50% of maximal contraction (IC50) value was 61.3μg/ml. The IC50 values of the EOCC on OT, PGF2α, and Ach-induced contractions were 113.0μg/ml, 94.7μg/ml, and 61.5μg/ml, respectively. Further in vitro studies indicated that the EOCC could restrain intracellular Ca2+ levels in favour of uterine relaxation.ConclusionBoth in vivo and in vitro results suggest that the EOCC possesses significant spasmolytic effect on uterine contraction. Thus, the EOCC yields a possible therapeutic choice for the prevention and treatment of primary dysmenorrhea.
Graphical abstract
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Interprofessional education in pediatrics − child protection and family services as a teaching example
Publication date: Available online 25 May 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Christine Straub, Marcus Krüger, Sebastian Bode
Interprofessional collaboration between different professional groups in the health care system is essential to efficient and effective patient care. Especially in pediatrics, in the field of child protection, and family services it is mandatory to involve experts from different health-care professions to optimize support for children and their families. Interprofessional education in medical schools and specifically in pediatrics is rare in Germany, but is called for by the German National Competence Based Catalogue of Learning Objectives for Undergraduate Medical Education (NKLM).We developed an interprofessional course aimed at bringing medical students together with students of psychology, social work, clinical education, and educational science to learn from, about and with each other in the context of child protection and family services. This offers opportunities for all participants to understand profession-specific competencies, roles, attitudes, and limits of their professional roles. The course is led by an interprofessional teaching tandem (social scientist & physician); further input is provided by other health and social care professionals. After the students get a brief overview about the requirements for a successful interprofessional cooperation they solve case studies in interprofessional teams with online support by the teaching tandem. We assess the feasibility and acceptability of this interprofessional course and describe challenges encountered when conducting this kind of learning concept for health care professions.All conducted courses over five consecutive terms were evaluated with an arithmetic mean of AM=1.32 on a 6-point scale (1="excellent", 6="insufficient"), the teaching tandem was evaluated with AM=1.1. All participants (N=85 complete evaluations) voted for the course to be continued in the following terms. Especially the opportunity to discuss cases with students from different degree programs was highly valued as were interprofessional discussions and more in-depth understanding of other professions' competencies and roles.
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Platelet-released growth factors induce psoriasin in keratinocytes: Implications for the cutaneous barrier
Publication date: Available online 25 May 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Andreas Bayer, Justus Lammel, Sebastian Lippross, Tim Klüter, Peter Behrendt, Mersedeh Tohidnezhad, Thomas Pufe, Jochen Cremer, Holger Jahr, Franziska Rademacher, Regine Gläser, Jürgen Harder
Millions of patients around the world suffer minor or major extremity amputation due to progressive wound healing complications of chronic or infected wounds, the therapy of which remains a challenge. One emerging therapeutic option for the treatment of these complicated wounds is the local application of an autologous thrombocytes concentrate lysate (e.g. platelet-released growth factors ((PRGF)) or Vivostat PRF®) that contains a multitude of chemokines, cytokines and growth factors and is therefore supposed to stimulate the complex wound healing process. Although PRGF and Vivostat PRF® are already used successfully to support healing of chronic, hard-to-heal and infected wounds the underlying molecular mechanisms are not well understood.Psoriasin, also termed S100A7, is a multifunctional antimicrobial protein expressed in keratinocytes and is involved in various processes such as wound-healing, angiogenesis, innate immunity and immune-modulation. In this study, we investigated the influence of PRGF on psoriasin expression in human primary keratinocytes in vitro and the influence of Vivostat PRF® on psoriasin expression in experimentally generated skin wounds in vivo.PRGF treatment of primary keratinocytes caused a significant concentration- and time- dependent increase of psoriasin gene and protein expression in vitro that were partially mediated by the epidermal growth factor receptor (EGFR) and the interleukin-6 receptor (IL-6R). In accordance with these cell culture data, Vivostat PRF® induced a significant psoriasin gene and protein expression when applied to artificially generated skin wounds in vivo. The observed psoriasin induction in keratinocytes may contribute to the wound healing-promoting effects of therapeutically used thrombocyte concentrate lysates.
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