431 research outputs found

    Concurrent use of prescription drugs and herbal medicinal products in older adults: a systematic review protocol

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    Background: There has been a global increase in the use of herbal medicinal products (HMPs). About a quarter of UK adults use HMPs, bought over the counter by self-prescription and often not disclosed to healthcare professionals. Potential herb-drug interaction is a clinical concern, with older people at greater risk because of co-morbidities and slower clearance of pharmacologically active compounds. While there is a good understanding of general herbal medicine use by older people, less is known about the extent and implications of concurrent use with prescription medicines. The aim of this systematic review is to assess the prevalence, patterns, safety issues and other factors associated with concurrent prescription and herbal medicines use among older adults. Methods/design: Systematic electronic searches of MEDLINE, PsychINFO, Excerpta Medica dataBASE (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), Web of Science and Cochrane from inception till present for studies reporting the concurrent use of prescription medicines with HMPs in older adults (≥65 years). Lateral searching via related citation (PubMed) and checking reference lists of identified studies will be performed. Two reviewers will independently screen studies, extract data and appraise methodological quality using the Joanna Briggs Institute checklist for prevalence data and the Critical Appraisal Skills Programme (CASP) checklist. Qualitative and quantitative studies from all settings will be included. Non-empirical papers, in vitro experiments and animal studies will be excluded. Primary outcomes are prevalence and patterns of concurrent use, number and types of prescription and HMPs and adverse reactions reported. Secondary outcomes are disclosure of HMP use to healthcare professionals and cost of HMPs. A narrative synthesis of included studies will be performed to summarise the evidence. Discussion: This review will synthesise and critically appraise current knowledge on the concurrent use of drugs and HMPs by older adults and thus provide a better understanding of the issue. It will also identify any gaps in knowledge. By establishing safety issues associated with concurrent use, it will also inform strategies that can help practitioners to identify and manage older people at potential risk of herb-drug interactions. Systematic review registration: PROSPERO CRD4201400909

    PTPN11 mutation manifesting as LEOPARD syndrome associated with hypertrophic plexi and neuropathic pain.

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    BACKGROUND: LEOPARD syndrome (LS) belongs to the family of neuro-cardio-facio-cutaneous syndromes, which include Neurofibromatosis-1 (NF1), Noonan syndrome, Costello Syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair and Legius syndrome. These conditions are caused by mutations in genes encoding proteins involved in the RAS-MAPK cellular pathway. Clinical heterogeneity and phenotype overlaps across those different syndromes is already recognized. CASE PRESENTATION: We hereby report a heterozygous de novo mutation in the PTPN11 gene (c.1403C > T) manifesting with a clinical picture of LS during childhood, and later development of neuropathic pain with hypertrophic plexi, which are typically observed in NF1 but have not been reported in LS. CONCLUSION: LS caused by PTPN11 mutations may be associated with hypertrophic roots and plexi. Consequently, clinicians should be aware of the possible development of neuropathic pain and consider specific diagnostic work-up and management

    Towards Learned Emulation of Interannual Water Isotopologue Variations in General Circulation Models

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    Simulating abundances of stable water isotopologues, i.e. molecules differing in their isotopic composition, within climate models allows for comparisons with proxy data and, thus, for testing hypotheses about past climate and validating climate models under varying climatic conditions. However, many models are run without explicitly simulating water isotopologues. We investigate the possibility to replace the explicit physics-based simulation of oxygen isotopic composition in precipitation using machine learning methods. These methods estimate isotopic composition at each time step for given fields of surface temperature and precipitation amount. We implement convolutional neural networks (CNNs) based on the successful UNet architecture and test whether a spherical network architecture outperforms the naive approach of treating Earth's latitude-longitude grid as a flat image. Conducting a case study on a last millennium run with the iHadCM3 climate model, we find that roughly 40\% of the temporal variance in the isotopic composition is explained by the emulations on interannual and monthly timescale, with spatially varying emulation quality. A modified version of the standard UNet architecture for flat images yields results that are equally good as the predictions by the spherical CNN. We test generalization to last millennium runs of other climate models and find that while the tested deep learning methods yield the best results on iHadCM3 data, the performance drops when predicting on other models and is comparable to simple pixel-wise linear regression. An extended choice of predictor variables and improving the robustness of learned climate--oxygen isotope relationships should be explored in future work

    Preconditioning triggered by carbon monoxide (CO) provides neuronal protection following perinatal hypoxia-ischemia

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    Perinatal hypoxia-ischemia is a major cause of acute mortality in newborns and cognitive and motor impairments in children. Cerebral hypoxia-ischemia leads to excitotoxicity and necrotic and apoptotic cell death, in which mitochondria play a major role. Increased resistance against major damage can be achieved by preconditioning triggered by subtle insults. CO, a toxic molecule that is also generated endogenously, may have a role in preconditioning as low doses can protect against inflammation and apoptosis. In this study, the role of CO-induced preconditioning on neurons was addressed in vitro and in vivo. The effect of 1 h of CO treatment on neuronal death (plasmatic membrane permeabilization and chromatin condensation) and bcl-2 expression was studied in cerebellar granule cells undergoing to glutamate-induced apoptosis. CO's role was studied in vivo in the Rice-Vannucci model of neonatal hypoxia-ischemia (common carotid artery ligature +75 min at 8% oxygen). Apoptotic cells, assessed by Nissl staining were counted with a stereological approach and cleaved caspase 3-positive profiles in the hippocampus were assessed. Apoptotic hallmarks were analyzed in hippocampal extracts by Western Blot. CO inhibited excitotoxicity-induced cell death and increased Bcl-2 mRNA in primary cultures of neurons. In vivo, CO prevented hypoxia-ischemia induced apoptosis in the hippocampus, limited cytochrome c released from mitochondria and reduced activation of caspase-3. Still, Bcl-2 protein levels were higher in hippocampus of CO pre-treated rat pups. Our results show that CO preconditioning elicits a molecular cascade that limits neuronal apoptosis. This could represent an innovative therapeutic strategy for high-risk cerebral hypoxia-ischemia patients, in particular neonates

    Inequality and violent crime: evidence from data on robbery and violent theft

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    This article argues that the link between income inequality and violent property crime might be spurious, complementing a similar argument in prior analysis by the author on the determinants of homicide. In contrast, Fajnzylber, Lederman & Loayza (1998; 2002a, b) provide seemingly strong and robust evidence that inequality causes a higher rate of both homicide and robbery/violent theft even after controlling for country-specific fixed effects. Our results suggest that inequality is not a statistically significant determinant, unless either country-specific effects are not controlled for or the sample is artificially restricted to a small number of countries. The reason why the link between inequality and violent property crime might be spurious is that income inequality is likely to be strongly correlated with country-specific fixed effects such as cultural differences. A high degree of inequality might be socially undesirable for any number of reasons, but that it causes violent crime is far from proven

    A comparison of plot-based satellite and Earth system model estimates of tropical forest net primary production

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    Net primary production (NPP) by plants represents the largest annual flux of carbon dioxide (CO2) from the atmosphere to the terrestrial biosphere, playing a critical role in the global carbon (C) cycle and the Earth’s climate. Rates of NPP in tropical forests are thought to be among the highest on Earth, but debates about the magnitude, patterns, and controls of NPP in the tropics highlight uncertainty in our understanding of how tropical forests may respond to environmental change. Here, we compared tropical NPP estimates generated using three common approaches: (1) field-based methods scaled from plot-level measurements of plant biomass, (2) radiation-based methods that model NPP from satellite-derived radiation absorption by plants, (3) and biogeochemical model-based methods. For undisturbed tropical forests as a whole, the three methods produced similar NPP estimates (i.e. about 10 Pg C yr1). However, the three different approaches produced vastly different patterns of NPP both in space and through time, suggesting that our understanding of tropical NPP is poor and that our ability to predict the response of NPP in the tropics to environmental change is limited. To address this shortcoming, we suggest the development of an expanded, high-density, permanent network of sites where NPP is continuously evaluated using multiple approaches. Well-designed NPP megatransects that include a high-density plot network would significantly increase the accuracy and certainty in the observed rates and patterns of tropical NPP and improve the reliability of Earth system models used to predict NPP–carbon cycle–climate interactions into the futur

    Neuro-axonal injury in COVID-19: the role of systemic inflammation and SARS-CoV-2 specific immune response

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    Background: In coronavirus disease-2019 (COVID-19) patients, there is increasing evidence of neuronal injury by the means of elevated serum neurofilament light chain (sNfL) levels. However, the role of systemic inflammation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific immune response with regard to neuronal injury has not yet been investigated. Methods: In a prospective cohort study, we recruited patients with mild–moderate (n = 39) and severe (n = 14) COVID-19 and measured sNfL levels, cytokine concentrations, SARS-CoV-2-specific antibodies including neutralizing antibody titers, and cell-mediated immune responses at enrollment and at 28(±7) days. We explored the association of neuro-axonal injury as by the means of sNfL measurements with disease severity, cytokine levels, and virus-specific immune responses. Results: sNfL levels, as an indicator for neuronal injury, were higher at enrollment and increased during follow-up in severely ill patients, whereas during mild–moderate COVID-19, sNfL levels remained unchanged. Severe COVID-19 was associated with increased concentrations of cytokines assessed [interleukin (IL)-6, IL-8, interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α)], higher anti-spike IgG and anti-nucleocapsid IgG concentrations, and increased neutralizing antibody titers compared with mild–moderate disease. Patients with more severe disease had higher counts of defined SARS-CoV-2-specific T cells. Increases in sNfL concentrations from baseline to day 28(±7) positively correlated with anti-spike protein IgG antibody levels and with titers of neutralizing antibodies. Conclusion: Severe COVID-19 is associated with increased serum concentration of cytokines and subsequent neuronal injury as reflected by increased levels of sNfL. Patients with more severe disease developed higher neutralizing antibody titers and higher counts of SARS-CoV-2-specific T cells during the course of COVID-19 disease. Mounting a pronounced virus-specific humoral and cell-mediated immune response upon SARS-CoV-2 infection did not protect from neuro-axonal damage as by the means of sNfL levels
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