The redefinition of neuropathic pain as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system," which was suggested by the International Association for the ...Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) in 2008, has been widely accepted. In contrast, the proposed grading system of possible, probable, and definite neuropathic pain from 2008 has been used to a lesser extent. Here, we report a citation analysis of the original NeuPSIG grading paper of 2008, followed by an analysis of its use by an expert panel and recommendations for an improved grading system. As of February, 2015, 608 eligible articles in Scopus cited the paper, 414 of which cited the neuropathic pain definition. Of 220 clinical studies citing the paper, 56 had used the grading system. The percentage using the grading system increased from 5% in 2009 to 30% in 2014. Obstacles to a wider use of the grading system were identified, including (1) questions about the relative significance of confirmatory tests, (2) the role of screening tools, and (3) uncertainties about what is considered a neuroanatomically plausible pain distribution. Here, we present a revised grading system with an adjusted order, better reflecting clinical practice, improvements in the specifications, and a word of caution that even the "definite" level of neuropathic pain does not always indicate causality. In addition, we add a table illustrating the area of pain and sensory abnormalities in common neuropathic pain conditions and propose areas for further research.
Pre-diabetes and diabetes are a global epidemic, and the associated neuropathic complications create a substantial burden on both the afflicted patients and society as a whole. Given the enormity of ...the problem and the lack of effective therapies, there is a pressing need to understand the mechanisms underlying diabetic neuropathy (DN). In this review, we present the structural components of the peripheral nervous system that underlie its susceptibility to metabolic insults and then discuss the pathways that contribute to peripheral nerve injury in DN. We also discuss systems biology insights gleaned from the recent advances in biotechnology and bioinformatics, emerging ideas centered on the axon-Schwann cell relationship and associated bioenergetic crosstalk, and the rapid expansion of our knowledge of the mechanisms contributing to neuropathic pain in diabetes. These recent advances in our understanding of DN pathogenesis are paving the way for critical mechanism-based therapy development.
Nearly a quarter of a billion people worldwide have diabetic neuropathy. However, despite high morbidity, there are no disease-modifying therapies for the disorder. Four international experts review new experimental advances in the field with an eye toward future mechanism-based therapies.
Although drugs are intended to be selective, at least some bind to several physiological targets, explaining side effects and efficacy. Because many drug-target combinations exist, it would be useful ...to explore possible interactions computationally. Here we compared 3,665 US Food and Drug Administration (FDA)-approved and investigational drugs against hundreds of targets, defining each target by its ligands. Chemical similarities between drugs and ligand sets predicted thousands of unanticipated associations. Thirty were tested experimentally, including the antagonism of the beta(1) receptor by the transporter inhibitor Prozac, the inhibition of the 5-hydroxytryptamine (5-HT) transporter by the ion channel drug Vadilex, and antagonism of the histamine H(4) receptor by the enzyme inhibitor Rescriptor. Overall, 23 new drug-target associations were confirmed, five of which were potent (<100 nM). The physiological relevance of one, the drug N,N-dimethyltryptamine (DMT) on serotonergic receptors, was confirmed in a knockout mouse. The chemical similarity approach is systematic and comprehensive, and may suggest side-effects and new indications for many drugs.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
For most optoelectronic applications of graphene, a thorough understanding of the processes that govern energy relaxation of photoexcited carriers is essential. The ultrafast energy relaxation in ...graphene occurs through two competing pathways: carrier–carrier scattering, creating an elevated carrier temperature, and optical phonon emission. At present, it is not clear what determines the dominating relaxation pathway. Here we reach a unifying picture of the ultrafast energy relaxation by investigating the terahertz photoconductivity, while varying the Fermi energy, photon energy and fluence over a wide range. We find that sufficiently low fluence (≲4 μJ/cm2) in conjunction with sufficiently high Fermi energy (≳0.1 eV) gives rise to energy relaxation that is dominated by carrier–carrier scattering, which leads to efficient carrier heating. Upon increasing the fluence or decreasing the Fermi energy, the carrier heating efficiency decreases, presumably due to energy relaxation that becomes increasingly dominated by phonon emission. Carrier heating through carrier–carrier scattering accounts for the negative photoconductivity for doped graphene observed at terahertz frequencies. We present a simple model that reproduces the data for a wide range of Fermi levels and excitation energies and allows us to qualitatively assess how the branching ratio between the two distinct relaxation pathways depends on excitation fluence and Fermi energy.
The conversion of light into free electron-hole pairs constitutes the key process in the fields of photodetection and photovoltaics. The efficiency of this process depends on the competition of ...different relaxation pathways and can be greatly enhanced when photoexcited carriers do not lose energy as heat, but instead transfer their excess energy into the production of additional electron-hole pairs through carrier-carrier scattering processes. Here we use optical pump-terahertz probe measurements to probe different pathways contributing to the ultrafast energy relaxation of photoexcited carriers. Our results indicate that carrier-carrier scattering is highly efficient, prevailing over optical-phonon emission in a wide range of photon wavelengths and leading to the production of secondary hot electrons originating from the conduction band. As hot electrons in graphene can drive currents, multiple hot-carrier generation makes graphene a promising material for highly efficient broadband extraction of light energy into electronic degrees of freedom, enabling high-efficiency optoelectronic applications. PUBLICATION ABSTRACT
Abstract
This review gives first a brief view of the potential availability of sustainable energy. It is clear that over 100 times more solar photovoltaic energy than necessary is readily accessible ...and that practically available wind alone may deliver sufficient energy supply to the world. Due to the intermittency of these sources, effective and inexpensive energy-conversion and storage technology is needed. Motivation for the possible electrolysis application of reversible solid-oxide cells (RSOCs), including a comparison of power-to-fuel/fuel-to-power to other energy-conversion and storage technologies is presented. RSOC electrochemistry and chemistry of H2O, CO2, H2, CO, CnHm (hydrocarbons) and NH3, including thermodynamics and cell performance, are described. The mechanical strength of popular cell supports is outlined, and newly found stronger materials are mentioned. Common cell-degradation mechanisms, including the effect of common impurities in gases and materials (such as S and Si), plus the deleterious effects of carbon deposition in the fuel electrode are described followed by explanations of how to avoid or ease the consequences. Visions of how RSOCs powered by sustainable energy may be applied on a large scale for the transportation sector via power-to-fuel technology and for integration with the electrical grid together with seasonal storage are presented. Finally, a brief comparison of RSOCs to other electrolysis cells and an outlook with examples of actions necessary to commercialize RSOC applications are sketched.
The unstructured-mesh SWAN spectral wave model and the ADCIRC shallow-water circulation model have been integrated into a tightly-coupled SWAN
+
ADCIRC model. The model components are applied to an ...identical, unstructured mesh; share parallel computing infrastructure; and run sequentially in time. Wind speeds, water levels, currents and radiation stress gradients are vertex-based, and therefore can be passed through memory or cache to each model component. Parallel simulations based on domain decomposition utilize identical sub-meshes, and the communication is highly localized. Inter-model communication is intra-core, while intra-model communication is inter-core but is local and efficient because it is solely on adjacent sub-mesh edges. The resulting integrated SWAN
+
ADCIRC system is highly scalable and allows for localized increases in resolution without the complexity or cost of nested meshes or global interpolation between heterogeneous meshes. Hurricane waves and storm surge are validated for Hurricanes Katrina and Rita, demonstrating the importance of inclusion of the wave-circulation interactions, and efficient performance is demonstrated to 3062 computational cores.
Norway has the largest salmon-farming industry in the world, an industry that is still growing, and in recent years production of marine species like Atlantic cod has also increased. At the same ...time, Norway has the world's largest wild stock of Atlantic salmon and has fjord systems and ocean areas rich in wild marine fish species which form the basis of a large fishing industry. As the aquaculture industry grows and diversifies, there is concern about the potential effects of pathogens spreading from farmed fish to wild populations. The overall health situation in Norwegian aquaculture is good, but some pathogens are not controlled effectively. In particular, salmon lice produced in farms may cause problems for wild salmonids and other parasites may be abundant too. Also, viral diseases in Atlantic salmon and bacterial diseases in Atlantic cod give rise to several disease outbreaks annually. The open design of most aquaculture systems allows the transmission of pathogens from the environment or from wild fish to the farmed fish. The objective of this review is to provide an overview of current knowledge of disease interaction and pathogen exchange between farmed and wild fish populations, with emphasis on Norwegian condition. In addition, the paper contains an evaluation of research methods that would be useful in expanding knowledge of pathogen exchange between wild and farmed fish, and in surveys of diseases in wild fish populations. The impact of pathogen transfer from farmed fish to economically important wild fish populations is assessed together with risk analysis considering possible consequences of pathogen exchange between farmed and wild fish. Finally, the review contains suggestions for future research that will increase the knowledge in the field.
Abstract
STUDY QUESTION
Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by ...nuchal translucency thickness and pregnancy loss?
SUMMARY ANSWER
Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester.
WHAT IS KNOWN ALREADY
Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies.
STUDY DESIGN, SIZE, DURATION
Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent.
MAIN RESULTS AND THE ROLE OF CHANCE
Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08–24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies.
LIMITATIONS, REASONS FOR CAUTION
These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection.
WIDER IMPLICATION OF THE FINDINGS
Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection.
STUDY FUNDING/COMPETING INTEREST(S)
Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet’s research fund. H.S.N. has received speaker’s fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker’s fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest.
TRIAL REGISTRATION NUMBER
N/A
Background
Cholangiocarcinoma (CCA) is associated with poor survival and therapeutic nihilism. To date, there has not been an examination of the surgical management of CCA at a population level.
...Methods
Using the Surveillance, Epidemiology and End Results (SEER) database, we identified all patients with intrahepatic CCA diagnosed between 1988 and 2003. Tumors categorized as a single, unilobar lesion with no evidence of vascular invasion were defined as localized. It was then determined whether patients received cancer directed surgery (CDS). Multivariable logistic regression was used to evaluate factors associated with CDS in patients with localized disease. The influence of CDS on overall survival (OS) was evaluated using Kaplan–Meier curves and Cox proportional hazards modeling.
Results
Only 446 (12%) of 3,756 patients with intrahepatic CCA underwent CDS. On multivariable analysis, non-Klatskin tumor (
p
< 0.01) and younger age (
p
= 0.02) was associated with CDS. Localized disease was strongly associated with CDS (
p
< 0.01); however, only 91 (37%) of these 248 patients underwent CDS. Of patients with localized disease, those who had CDS had significantly better survival than those who did not (
p
< 0.01), with median overall survival (OS) of 44 months versus 8 months, and five-year OS of 42% versus 4%, respectively.
Conclusions
Patients with localized CCA who are selected for CDS are strongly associated with improved survival, with rates approaching that found in single institution studies. However, many patients with localized tumors do not receive potentially curative cancer-directed surgery. Further study is warranted to address the barriers to the delivery of appropriate care to these patients.
PDF
