scholarly journals Facts and Fiction: The Impact of Hypothermia on Molecular Mechanisms following Major Challenge

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Michael Frink ◽  
Sascha Flohé ◽  
Martijn van Griensven ◽  
Philipp Mommsen ◽  
Frank Hildebrand
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Randomized Clinical Trials ◽  
Severe Trauma ◽  
Accidental Hypothermia ◽  
Induced Hypothermia ◽  
Trauma Patients ◽  
Protective Effects ◽  
Elective Cardiac Surgery ◽  
The Impact

Numerous multiple trauma and surgical patients suffer from accidental hypothermia. While induced hypothermia is commonly used in elective cardiac surgery due to its protective effects, accidental hypothermia is associated with increased posttraumatic complications and even mortality in severely injured patients. This paper focuses on protective molecular mechanisms of hypothermia on apoptosis and the posttraumatic immune response. Although information regarding severe trauma is limited, there is evidence that induced hypothermia may have beneficial effects on the posttraumatic immune response as well as apoptosis in animal studies and certain clinical situations. However, more profound knowledge of mechanisms is necessary before randomized clinical trials in trauma patients can be initiated.

The Impact of Ultraviolet Radiation on Barrier Function in Human Skin: Molecular Mechanisms and Topical Therapeutics

2019 ◽  
Vol 25 (40) ◽  
pp. 5503-5511 ◽  
Author(s):  
Abdulaziz Alhasaniah ◽  
Michael J. Sherratt ◽  
Catherine A. O'Neill
Keyword(s):  
Ultraviolet Radiation ◽  
Barrier Function ◽  
Molecular Mechanisms ◽  
Transepidermal Water Loss ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Epidermal Barrier ◽  
Positive Effects ◽  
Terrestrial Mammals ◽  
The Impact

A competent epidermal barrier is crucial for terrestrial mammals. This barrier must keep in water and prevent entry of noxious stimuli. Most importantly, the epidermis must also be a barrier to ultraviolet radiation (UVR) from the sunlight. Currently, the effects of ultraviolet radiation on epidermal barrier function are poorly understood. However, studies in mice and more limited work in humans suggest that the epidermal barrier becomes more permeable, as measured by increased transepidermal water loss, in response UVR, at doses sufficiently high to induce erythema. The mechanisms may include disturbance in the organisation of lipids in the stratum corneum (the outermost layer of the epidermis) and reduction in tight junction function in the granular layer (the first living layer of the skin). By contrast, suberythemal doses of UVR appear to have positive effects on epidermal barrier function. Topical sunscreens have direct and indirect protective effects on the barrier through their ability to block UV and also due to their moisturising or occlusive effects, which trap water in the skin, respectively. Some topical agents such as specific botanical extracts have been shown to prevent the loss of water associated with high doses of UVR. In this review, we discuss the current literature and suggest that the biology of UVR-induced barrier dysfunction, and the use of topical products to protect the barrier, are areas worthy of further investigation.

scholarly journals The Impact of Accidental Hypothermia on Mortality in Trauma Patients Overall and Patients with Traumatic Brain Injury Specifically: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 44 (12) ◽  
pp. 4106-4117
Author(s):  
David Rösli ◽  
Beat Schnüriger ◽  
Daniel Candinas ◽  
Tobias Haltmeier
Keyword(s):  
Systematic Review ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Hospital Mortality ◽  
Meta Analysis ◽  
Accidental Hypothermia ◽  
Trauma Patients ◽  
Qualitative Synthesis ◽  
Pubmed Database ◽  
The Impact

Abstract Background Accidental hypothermia is a known predictor for worse outcomes in trauma patients, but has not been comprehensively assessed in a meta-analysis so far. The aim of this systematic review and meta-analysis was to investigate the impact of accidental hypothermia on mortality in trauma patients overall and patients with traumatic brain injury (TBI) specifically. Methods This is a systematic review and meta-analysis using the Ovid Medline/PubMed database. Scientific articles reporting accidental hypothermia and its impact on outcomes in trauma patients were included in qualitative synthesis. Studies that compared the effect of hypothermia vs. normothermia at hospital admission on in-hospital mortality were included in two meta-analyses on (1) trauma patients overall and (2) patients with TBI specifically. Meta-analysis was performed using a Mantel–Haenszel random-effects model. Results Literature search revealed 264 articles. Of these, 14 studies published 1987–2018 were included in the qualitative synthesis. Seven studies qualified for meta-analysis on trauma patients overall and three studies for meta-analysis on patients with TBI specifically. Accidental hypothermia at admission was associated with significantly higher mortality both in trauma patients overall (OR 5.18 [95% CI 2.61–10.28]) and patients with TBI specifically (OR 2.38 [95% CI 1.53–3.69]). Conclusions In the current meta-analysis, accidental hypothermia was strongly associated with higher in-hospital mortality both in trauma patients overall and patients with TBI specifically. These findings underscore the importance of measures to avoid accidental hypothermia in the prehospital care of trauma patients.

scholarly journals Prediction and evolution of the molecular fitness of SARS-CoV-2 variants: Introducing SpikePro

2021 ◽  
Author(s):  
Fabrizio Pucci ◽  
Marianne Rooman
Keyword(s):  
Immune Response ◽  
Neutralizing Antibodies ◽  
Molecular Mechanisms ◽  
Population Level ◽  
Critical Issue ◽  
Spike Protein ◽  
Human Immune Response ◽  
Human Immune ◽  
The Stability ◽  
The Impact

The understanding of the molecular mechanisms driving the fitness of the SARS-CoV-2 virus and its mutational evolution is still a critical issue. We built a simplified computational model, called SpikePro, to predict the SARS-CoV-2 fitness from the amino acid sequence and structure of the spike protein. It contains three contributions: the viral transmissibility predicted from the stability of the spike protein, the infectivity computed in terms of the affinity of the spike protein for the ACE2 receptor, and the ability of the virus to escape from the human immune response based on the binding affinity of the spike protein for a set of neutralizing antibodies. Our model reproduces well the available experimental, epidemiological and clinical data on the impact of variants on the biophysical characteristics of the virus. For example, it is able to identify circulating viral strains that, by increasing their fitness, recently became dominant at the population level. SpikePro is a useful instrument for the genomic surveillance of the SARS-CoV-2 virus, since it predicts in a fast and accurate way the emergence of new viral strains and their dangerousness. It is freely available in the GitHub repository github.com/3BioCompBio/SpikeProSARS-CoV-2.

scholarly journals Obesity and COVID-19: Molecular Mechanisms Linking Both Pandemics

2020 ◽  
Vol 21 (16) ◽  
pp. 5793 ◽  
Author(s):  
Andreas Ritter ◽  
Nina-Naomi Kreis ◽  
Frank Louwen ◽  
Juping Yuan
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Mesenchymal Stem Cells ◽  
Systemic Inflammation ◽  
Molecular Mechanisms ◽  
Airway Epithelial Cells ◽  
Metabolic Dysfunction ◽  
Health Crisis ◽  
Susceptible Population ◽  
The Impact

The coronavirus disease 2019 COVID-19 pandemic is rapidly spreading worldwide and is becoming a major public health crisis. Increasing evidence demonstrates a strong correlation between obesity and the COVID-19 disease. We have summarized recent studies and addressed the impact of obesity on COVID-19 in terms of hospitalization, severity, mortality, and patient outcome. We discuss the potential molecular mechanisms whereby obesity contributes to the pathogenesis of COVID-19. In addition to obesity-related deregulated immune response, chronic inflammation, endothelium imbalance, metabolic dysfunction, and its associated comorbidities, dysfunctional mesenchymal stem cells/adipose-derived mesenchymal stem cells may also play crucial roles in fueling systemic inflammation contributing to the cytokine storm and promoting pulmonary fibrosis causing lung functional failure, characteristic of severe COVID-19. Moreover, obesity may also compromise motile cilia on airway epithelial cells and impair functioning of the mucociliary escalators, reducing the clearance of severe acute respiratory syndrome coronavirus (SARS-CoV-2). Obese diseased adipose tissues overexpress the receptors and proteases for the SARS-CoV-2 entry, implicating its possible roles as virus reservoir and accelerator reinforcing violent systemic inflammation and immune response. Finally, anti-inflammatory cytokines like anti-interleukin 6 and administration of mesenchymal stromal/stem cells may serve as potential immune modulatory therapies for supportively combating COVID-19. Obesity is conversely related to the development of COVID-19 through numerous molecular mechanisms and individuals with obesity belong to the COVID-19-susceptible population requiring more protective measures.

scholarly journals HTLV-1 ORF-I Encoded Proteins and the Regulation of Host Immune Response: Viral Induced Dysregulation of Intracellular Signaling

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Carolina Rosadas ◽  
Marzia Puccioni-Sohler
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
T Cell ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
T Cell Proliferation ◽  
Human T Cell ◽  
Encoded Proteins ◽  
Infected Cells ◽  
The Impact

The human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus associated with both proliferative and inflammatory disorders. This virus causes a persistent infection, mainly in CD4+ T lymphocyte. The ability to persist in the host is associated with the virus capacity to evade the immune response and to induce infected T-cell proliferation, once the HTLV-1 maintains the infection mainly by clonal expansion of infected cells. There are several evidences that ORF-I encoded proteins, such as p12 and p8, play an important role in this context. The present study will review the molecular mechanisms that HTLV-1 ORF-I encoded proteins have to induce dysregulation of intracellular signaling, in order to escape from immune response and to increase the infected T-cell proliferation rate. The work will also address the impact of ORF-I mutations on the human host and perspectives in this study field.

scholarly journals Splenectomy is Associated with Altered Leukocyte Kinetics after Severe Trauma

2020 ◽  
Author(s):  
Michel Teuben ◽  
Arne Hollman ◽  
Taco J. Blokhuis ◽  
Roman Pfeifer ◽  
Roy Spijkerman ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Peripheral Blood ◽  
Cellular Immune Response ◽  
Severe Trauma ◽  
Multiple Organ ◽  
Liver Trauma ◽  
Trauma Patients ◽  
Severely Injured ◽  
Cellular Immune

Abstract Background Inadequate activation of the innate immune system after trauma can lead to severe complications such as Acute Respiratory Distress Syndrome and Multiple Organ Dysfunction Syndrome. The spleen is thought to modulate the cellular immune system. Furthermore, splenectomy is associated with improved outcome in severely injured trauma patients. We hypothesized that a splenectomy alters the cellular immune response in polytrauma.Methods All adult patients with an ISS ≥ 16 and suffering from splenic or hepatic injuries were selected from our prospective trauma database. Absolute leukocyte numbers in peripheral blood were measured. White blood cell kinetics during the first 14 days were compared between splenectomized patients, patients treated surgically for liver trauma and nonoperatively treated individuals.Results A total of 129 patients with a mean ISS of 29 were included. Admission characteristics and leukocyte numbers were similar in all groups, except for slightly impaired hemodynamic status in patients with operatively treated liver injuries. On admission, leukocytosis occurred in all groups. During the first 24 hours, leukopenia developed gradually, although significantly faster in the operatively treated patients. Thereafter, leukocyte levels normalized in all nonoperatively treated cases whereas leukocytosis persisted in operatively treated patients. This effect was significantly more prominent in splenectomized patients than all other conditions. Conclusions This study demonstrates that surgery for intra-abdominal injuries is associated with an early drop in leucocyte numbers in peripheral blood. Moreover, splenectomy in severely injured patients is associated with an altered cellular immune response reflected by a persistent state of prominent leukocytosis after trauma.

scholarly journals Peptidoglycan sensing by octopaminergic neurons modulates Drosophila oviposition

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
C Leopold Kurz ◽  
Bernard Charroux ◽  
Delphine Chaduli ◽  
Annelise Viallat-Lieutaud ◽  
Julien Royet
Keyword(s):  
Immune Response ◽  
Bacterial Infection ◽  
Immune Cells ◽  
Behavioral Change ◽  
Behavioral Response ◽  
Molecular Mechanisms ◽  
Egg Laying ◽  
Signaling Cascade ◽  
Host Behavior ◽  
The Impact

As infectious diseases pose a threat to host integrity, eukaryotes have evolved mechanisms to eliminate pathogens. In addition to develop strategies reducing infection, animals can engage in behaviors that lower the impact of the infection. The molecular mechanisms by which microbes impact host behavior are not well understood. We demonstrate that bacterial infection of Drosophila females reduces oviposition and that peptidoglycan, the component that activates Drosophila antibacterial response, is also the elicitor of this behavioral change. We show that peptidoglycan regulates egg-laying rate by activating NF-κB signaling pathway in octopaminergic neurons and that, a dedicated peptidoglycan degrading enzyme acts in these neurons to buffer this behavioral response. This study shows that a unique ligand and signaling cascade are used in immune cells to mount an immune response and in neurons to control fly behavior following infection. This may represent a case of behavioral immunity.

scholarly journals System Genetics Including Causal Inference Identify Immune Targets for Coronary Artery Disease and the Lifespan

2021 ◽  
Author(s):  
Valentin Bon-Baret ◽  
Arnaud Chignon ◽  
Marie-Chloé Boulanger ◽  
Zhonglin Li ◽  
Deborah Argaud ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Immune Response ◽  
Coronary Artery ◽  
Single Cell ◽  
Randomized Clinical Trials ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Artery Disease ◽  
Cell Expression ◽  
The Impact

Background - Randomized clinical trials indicate that the immune response plays a significant role in coronary artery disease (CAD), a disorder impacting the lifespan potential. However, the identification of targets critical to the immune response in atheroma is still hampered by a lack of solid inference. Methods - Herein, we implemented a system genetics approach to identify causally associated immune targets implicated in atheroma. We leveraged genome-wide association studies to perform mapping and Mendelian Randomization (MR) to assess causal associations between gene expression in blood cells with CAD and the lifespan. Expressed genes (eGenes) were prioritized in network and in single-cell expression derived from plaque immune cells. Results - Among 840 CAD-associated blood eGenes, 37 were predicted causally associated with CAD and 6 were also associated with the parental lifespan in MR. In multivariable MR, the impact of eGenes on the lifespan potential was mediated by the CAD risk. Predicted causal eGenes were central in network. FLT1 and CCR5 were identified as targets of approved drugs, whereas 22 eGenes were deemed tractable for the development of small molecules and/or antibodies. Analyses of plaque immune single-cell expression identified predicted causal eGenes enriched in macrophages ( GPX1 , C4orf3 ) and involved in ligand receptor interactions ( CCR5 ). Conclusions - We identified 37 blood eGenes predicted causally associated with CAD. The predicted expression for 6 eGenes impacted the lifespan potential through the risk of CAD. Prioritization based on network, annotations and single cell expression identified targets deemed tractable for the development of drugs and for drug repurposing.

scholarly journals The impact of blood type O on mortality of severe trauma patients: a retrospective observational study

Critical Care ◽  
2018 ◽  
Vol 22 (1) ◽  
Author(s):  
Wataru Takayama ◽  
Akira Endo ◽  
Hazuki Koguchi ◽  
Momoko Sugimoto ◽  
Kiyoshi Murata ◽  
...  
Keyword(s):  
Observational Study ◽  
Severe Trauma ◽  
Blood Type ◽  
Retrospective Observational Study ◽  
Trauma Patients ◽  
The Impact

scholarly journals Prevalence and outcome of abdominal vascular injury in severe trauma patients based on a TraumaRegister DGU international registry analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammad Esmaeil Barbati ◽  
Frank Hildebrand ◽  
Hagen Andruszkow ◽  
Rolf Lefering ◽  
Michael J. Jacobs ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Vascular Injury ◽  
Arterial Injury ◽  
Severe Trauma ◽  
Trauma Patients ◽  
Vascular Injuries ◽  
Comparable Rate ◽  
Venous Injury ◽  
The Impact ◽  
Abdominal Vascular Injuries

AbstractThis study details the etiology, frequency and effect of abdominal vascular injuries in patients after polytrauma based on a large registry of trauma patients. The impact of arterial, venous and mixed vascular injuries on patients’ outcome was of interest, as in particular the relevance of venous vessel injury may be underestimated and not adequately assessed in literature so far. All patients of TraumaRegister DGU with the following criteria were included: online documentation of european trauma centers, age 16–85 years, presence of abdominal vascular injury and Abbreviated Injury Scale (AIS) ≥ 3. Patients were divided in three groups of: arterial injury only, venous injury only, mixed arterial and venous injuries. Reporting in this study adheres to the STROBE criteria. A total of 2949 patients were included. All types of abdominal vessel injuries were more prevalent in patients with abdominal trauma followed by thoracic trauma. Rate of patients with shock upon admission were the same in patients with arterial injury alone (n = 606, 33%) and venous injury alone (n = 95, 32%). Venous trauma showed higher odds ratio for in-hospital mortality (OR: 1.48; 95% CI 1.10–1.98, p = 0.010). Abdominal arterial and venous injury in patients suffering from severe trauma were associated with a comparable rate of hemodynamic instability at the time of admission. 24 h as well as in-hospital mortality rate were similar in in patients with venous injury and arterial injury. Stable patients suspected of abdominal vascular injuries should be further investigated to exclude or localize the possible subtle venous injury.

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