82-fold and 280.83-fold that of the control. However, the expression of Bscasp-9 in the peripheral blood was upregulated only 8.33-fold higher than that in the control group. These results indicate that Bscasp-1, Bscasp-8 and Bscasp-9 are likely involved in response to viral and bacterial infection. © 2020 John Wiley & Sons Ltd.Post-earthquake fires are high-consequence events with extensive damage potential. They are also low-frequency events, so their nature remains underinvestigated. One difficulty in modeling post-earthquake ignition probabilities is reducing the model uncertainty attributed to the scarce source data. The data scarcity problem has been resolved by pooling the data indiscriminately collected from multiple earthquakes. However, this approach neglects the inter-earthquake heterogeneity in the regional and seasonal characteristics, which is indispensable for risk assessment of future post-earthquake fires. Thus, the present study analyzes the post-earthquake ignition probabilities of five major earthquakes in Japan from 1995 to 2016 (1995 Kobe, 2003 Tokachi-oki, 2004 Niigata-Chuetsu, 2011 Tohoku, and 2016 Kumamoto earthquakes) by a hierarchical Bayesian approach. As the ignition causes of earthquakes share a certain commonality, common prior distributions were assigned to the parameters, and samples were drawn from 0 Society for Risk Analysis.BACKGROUND In the absence of low-titer group O whole blood, conventional components are often transfused to hemorrhaging trauma patients in a ratio designed to replicate whole blood. However, there is still confusion surrounding how conventional components should be used to support traumatically injured bleeding patients, particularly concerning how platelets should be counted in a ratio-based approach and when the resuscitation can switch from a ratio-based to a laboratory-guided approach. CASE REPORT A traumatically injured patient, who was resuscitated with 10 units of red blood cells (RBCs), 6 units of plasma, 2 units of apheresis platelets, and 5 pools of cryoprecipitate is described. After hemostasis was achieved, and in the setting of an international normalized ratio of 1.2, the clinical team requested 4 additional units of plasma because "the patient was not resuscitated with a 11 ratio of RBCs to plasma." This case illustrates that misconceptions surrounding resuscitation with conventional components may lead to unnecessary transfusions in patients with normal laboratory values who have achieved hemostasis. CONCLUSIONS This report provides clarification as to how conventional components can be used for trauma resuscitation and why there is no need to transfuse additional plasma-containing components to achieve a desired ratio when the patient is no longer bleeding and laboratory values are within normal limits. Furthermore, each dose of platelets is suspended in roughly the equivalent of 1 additional unit of plasma that should also be considered in the cumulative dose of plasma administered when using a ratio-based approach. © 2020 AABB.The imperative to legitimise qualitative research approaches is not new. Indeed, in the 1960's Glaser and Strauss published their book on grounded theory 'to help provide a defense' for researchers engaging in 'creative' qualitative studies.1, p 7 Similarly, in this issue, Andreassen et al.2 bring the notion of focused ethnography to the medical education field as an applied research approach that provides a flexible way to research complexities inherent in the field. https://www.selleckchem.com/products/abt-199.html As they do so, they aim to clarify 'methodological confusion' around the different types of ethnographic approaches, and foster 'methodological clarity in future medical education research'. This article is protected by copyright. All rights reserved.The outbreak of a novel coronavirus (SARS-CoV-2) since December 2019 in Wuhan, the major transportation hub in central China, became an emergency of major international concern. While several etiological studies have begun to reveal the specific biological features of this virus, the epidemic characteristics need to be elucidated. Notably, a long incubation time was reported to be associated with SARS-CoV-2 infection, leading to adjustments in screening and control policies. To avoid the risk of virus spread, all potentially exposed subjects are required to be isolated for 14 days, which is the longest predicted incubation time. However, based on our analysis of a larger dataset available so far, we find there is no observable difference between the incubation time for SARS-CoV-2, severe acute respiratory syndrome coronavirus (SARS-CoV), and middle east respiratory syndrome coronavirus (MERS-CoV), highlighting the need for larger and well-annotated datasets. © 2020 Wiley Periodicals, Inc.Spinal muscular atrophy (SMA) is a severe autosomal recessive motor neuron disease caused by the loss of SMN1, which encodes a protein essential for motor neuron survival. SMA patients have one or more copies of an alternate SMN gene, SMN2, which is nearly identical to SMN1. SMN2 differs at a single nucleotide from SMN1 which results in the skipping of exon 7 in the mRNA and produces an unstable protein (SMNΔ7). Therapeutic approaches that have been undertaken include (1) replacement of SMN1 by gene delivery mediated by adeno-associated virus serotype 9 (AAV9) (Zolgensma), (2) correction of the aberrant SMN2 splicing using an antisense oligonucleotide (ASO) or small molecule (nusinersin, risdiplam), and (3) increased expression of SMN2 mediated by histone deacetylase (HDAC) inhibitors. Two of these three approaches have given rise to successful treatments for SMA, but they are very expensive, and their long-term safety is not well known. In addition, the ability of ASOs and viral vectors to reach their targets in the CNS with peripheral administration is limited. Small molecules may cross the brain-blood barrier when orally delivered and can be discontinued if needed to mitigate adverse effects. This Editorial highlights this study by Pagliarni et al. in which they used combined treatment of cell models of SMA with an ASO and an orally delivered HDAC inhibitor (panobinostat) to overcome the limitations of a single-therapeutic approach. Panobinostat enhanced the expression of SMN2, increasing the amount of SMN2 mRNA available for splicing correction mediated by the ASO. In addition, panobinostat increased exon 7 retention in the SMN2 mRNA. This combinatorial treatment might allow lower or less frequent ASO doses, reducing the need for repeated intrathecal administration. The combined effects of panobinostat and nusinersen can now be tested in SMA animal models to determine whether this approach will be translatable to patients. © 2020 International Society for Neurochemistry.
82-fold and 280.83-fold that of the control. However, the expression of Bscasp-9 in the peripheral blood was upregulated only 8.33-fold higher than that in the control group. These results indicate that Bscasp-1, Bscasp-8 and Bscasp-9 are likely involved in response to viral and bacterial infection. © 2020 John Wiley & Sons Ltd.Post-earthquake fires are high-consequence events with extensive damage potential. They are also low-frequency events, so their nature remains underinvestigated. One difficulty in modeling post-earthquake ignition probabilities is reducing the model uncertainty attributed to the scarce source data. The data scarcity problem has been resolved by pooling the data indiscriminately collected from multiple earthquakes. However, this approach neglects the inter-earthquake heterogeneity in the regional and seasonal characteristics, which is indispensable for risk assessment of future post-earthquake fires. Thus, the present study analyzes the post-earthquake ignition probabilities of five major earthquakes in Japan from 1995 to 2016 (1995 Kobe, 2003 Tokachi-oki, 2004 Niigata-Chuetsu, 2011 Tohoku, and 2016 Kumamoto earthquakes) by a hierarchical Bayesian approach. As the ignition causes of earthquakes share a certain commonality, common prior distributions were assigned to the parameters, and samples were drawn from 0 Society for Risk Analysis.BACKGROUND In the absence of low-titer group O whole blood, conventional components are often transfused to hemorrhaging trauma patients in a ratio designed to replicate whole blood. However, there is still confusion surrounding how conventional components should be used to support traumatically injured bleeding patients, particularly concerning how platelets should be counted in a ratio-based approach and when the resuscitation can switch from a ratio-based to a laboratory-guided approach. CASE REPORT A traumatically injured patient, who was resuscitated with 10 units of red blood cells (RBCs), 6 units of plasma, 2 units of apheresis platelets, and 5 pools of cryoprecipitate is described. After hemostasis was achieved, and in the setting of an international normalized ratio of 1.2, the clinical team requested 4 additional units of plasma because "the patient was not resuscitated with a 11 ratio of RBCs to plasma." This case illustrates that misconceptions surrounding resuscitation with conventional components may lead to unnecessary transfusions in patients with normal laboratory values who have achieved hemostasis. CONCLUSIONS This report provides clarification as to how conventional components can be used for trauma resuscitation and why there is no need to transfuse additional plasma-containing components to achieve a desired ratio when the patient is no longer bleeding and laboratory values are within normal limits. Furthermore, each dose of platelets is suspended in roughly the equivalent of 1 additional unit of plasma that should also be considered in the cumulative dose of plasma administered when using a ratio-based approach. © 2020 AABB.The imperative to legitimise qualitative research approaches is not new. Indeed, in the 1960's Glaser and Strauss published their book on grounded theory 'to help provide a defense' for researchers engaging in 'creative' qualitative studies.1, p 7 Similarly, in this issue, Andreassen et al.2 bring the notion of focused ethnography to the medical education field as an applied research approach that provides a flexible way to research complexities inherent in the field. https://www.selleckchem.com/products/abt-199.html As they do so, they aim to clarify 'methodological confusion' around the different types of ethnographic approaches, and foster 'methodological clarity in future medical education research'. This article is protected by copyright. All rights reserved.The outbreak of a novel coronavirus (SARS-CoV-2) since December 2019 in Wuhan, the major transportation hub in central China, became an emergency of major international concern. While several etiological studies have begun to reveal the specific biological features of this virus, the epidemic characteristics need to be elucidated. Notably, a long incubation time was reported to be associated with SARS-CoV-2 infection, leading to adjustments in screening and control policies. To avoid the risk of virus spread, all potentially exposed subjects are required to be isolated for 14 days, which is the longest predicted incubation time. However, based on our analysis of a larger dataset available so far, we find there is no observable difference between the incubation time for SARS-CoV-2, severe acute respiratory syndrome coronavirus (SARS-CoV), and middle east respiratory syndrome coronavirus (MERS-CoV), highlighting the need for larger and well-annotated datasets. © 2020 Wiley Periodicals, Inc.Spinal muscular atrophy (SMA) is a severe autosomal recessive motor neuron disease caused by the loss of SMN1, which encodes a protein essential for motor neuron survival. SMA patients have one or more copies of an alternate SMN gene, SMN2, which is nearly identical to SMN1. SMN2 differs at a single nucleotide from SMN1 which results in the skipping of exon 7 in the mRNA and produces an unstable protein (SMNΔ7). Therapeutic approaches that have been undertaken include (1) replacement of SMN1 by gene delivery mediated by adeno-associated virus serotype 9 (AAV9) (Zolgensma), (2) correction of the aberrant SMN2 splicing using an antisense oligonucleotide (ASO) or small molecule (nusinersin, risdiplam), and (3) increased expression of SMN2 mediated by histone deacetylase (HDAC) inhibitors. Two of these three approaches have given rise to successful treatments for SMA, but they are very expensive, and their long-term safety is not well known. In addition, the ability of ASOs and viral vectors to reach their targets in the CNS with peripheral administration is limited. Small molecules may cross the brain-blood barrier when orally delivered and can be discontinued if needed to mitigate adverse effects. This Editorial highlights this study by Pagliarni et al. in which they used combined treatment of cell models of SMA with an ASO and an orally delivered HDAC inhibitor (panobinostat) to overcome the limitations of a single-therapeutic approach. Panobinostat enhanced the expression of SMN2, increasing the amount of SMN2 mRNA available for splicing correction mediated by the ASO. In addition, panobinostat increased exon 7 retention in the SMN2 mRNA. This combinatorial treatment might allow lower or less frequent ASO doses, reducing the need for repeated intrathecal administration. The combined effects of panobinostat and nusinersen can now be tested in SMA animal models to determine whether this approach will be translatable to patients. © 2020 International Society for Neurochemistry.
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