Justification for a Nuclear Global Health Workforce: multidisciplinary analysis of risk, survivability & preparedness, with emphasis on the triage management of thermal burns

An assessment of the risks of nuclear conflict and the global preparedness to deal with such a catastrophe. Includes a proposal for triage and management of burn injuries based on a model of what would happen if there was a nuclear attack on Washington DC. Summarises the need for a global nuclear workforce to establish guidelines and strategies to address a nuclear event, the risk of which would appear to be increasingly likely given current world geopolitics

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) in association with an adenocarcinoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disorder and information on this disease is limited, especially with regard to its management and prognosis. It has become generally accepted that DIPNECH is a precursor lesion to pulmonary carcinoid tumors.</p> <p>Case presentation</p> <p>Here we report on a 60-year-old female patient with DIPNECH and an associated pulmonary adenocarcinoma.</p> <p>Conclusion</p> <p>This case contributes to a better understanding of the disorder and its associated pathologies.</p

Odkrycie i zastosowanie pegwisomantu: antagonisty hormonu wzrostu

Growth hormone (GH) is a well established participant in several complex physiological processes including growth, differentiation, and metabolism. Recombinant human GH is a drug that has been approved for use for several clinical conditions where the action of GH is diminished or completely lacking. Thus there is considerable interest in developing novel drugs that modify the function of GH. Only in the last several decades have the detailed structural features of GH along with its interaction with its receptor been elucidated. In this review we summarise the basic structural and functional properties of GH, its receptor and their interaction. In addition, we discuss the discovery and development of an effective GH receptor antagonist, pegvisomant, and summarise potential therapeutic uses of this drug. (Pol J Endocrinol 2007; 58 (4): 322-329)Hormon wzrostu (GH, growth hormone) uczestniczy w wielu fizjologicznych procesach dotyczących wzrastania, różnicowania i metabolizmu. Leczenie rekombinowanym ludzkim GH jest akceptowane w wielu schorzeniach wiążących się z całkowitym brakiem lub zmniejszeniem działania GH. Wynika stąd znaczne zainteresowanie rozwojem nowych leków mogących modyfikować czynność GH. Dopiero niedawno wyjaśniono dokładną strukturę GH i jego interakcje z receptorem. W niniejszej pracy autorzy podsumowują wiedzę dotyczącą podstawowej budowy GH, jego receptora i interakcji między nimi. Ponadto, omówiono odkrycie i rozwój skutecznego antagonisty receptora GH, pegvisomantu i przedstawiono potencjalne możliwości zastosowania terapeutycznego tego leku

Biomarker Testing for People With Advanced Lung Cancer in England

Introduction: Optimal management of people with advanced NSCLC depends on accurate identification of predictive markers. Yet, real-world data in this setting are limited. We describe the impact, timeliness, and outcomes of molecular testing for patients with advanced NSCLC and good performance status in England. // Methods: In collaboration with Public Health England, patients with stages IIIB to IV NSCLC, with an Eastern Cooperative Oncology Group performance status of 0 to 2, in England, between June 2017 and December 2017, were identified. All English hospitals were invited to record information. // Results: A total of 60 of 142 invited hospitals in England participated in this study and submitted data on 1157 patients. During the study period, 83% of patients with advanced adenocarcinoma underwent molecular testing for three recommended predictive biomarkers (EGFR, ALK, and programmed death-ligand 1). A total of 80% of patients with nonsquamous carcinomas on whom biomarker testing was performed had adequate tissue for analysis on initial sampling. First-line treatment with a tyrosine kinase inhibitor was received by 71% of patients with adenocarcinoma and a sensitizing EGFR mutation and by 59% of those with an ALK translocation. Of patients with no driver mutation and a programmed death-ligand 1 expression of greater than or equal to 50%, 47% received immunotherapy. // Conclusions: We present a comprehensive data set for molecular testing in England. Although molecular testing is well established in England, timeliness and uptake of targeted therapies should be improved

Fractional allele loss data indicate distinct genetic populations in the development of non-small-cell lung cancer.

Allelic imbalance or loss of heterozygosity (LOH) has been widely used to assess genetic instability in tumours, and high LOH on chromosome arms 3p, 9p and 17p has been considered to be a common event in non-small-cell lung cancer (NSCLC). We have investigated allelic imbalance in 45 NSCLCs using 92 microsatellite markers on 38 chromosome arms. LOH of 38% was observed on 3p using nine markers, 58% on 9p using 15 markers and 38% on 17p using five markers. Fractional allele loss (FAL) has been calculated for each tumour (FAL is the number of chromosome arms showing LOH/number of informative chromosome arms) and a median FAL value of 0.09 was obtained in the 45 NSCLCs studied. The LOH data were examined on the basis of FAL scores: low FAL (LFAL) (0.00-0.04), medium FAL (MFAL) (0.05-0.13) and high FAL (HFAL) (0.14-0.45) based symmetrically around the median FAL value of 0.09. Tumours with HFAL values showed a very clear polarisation of the LOH data on chromosome arms 3p, 9p and 17p, such that 80% showed loss on 3p, 80% on 9p and 73% on 17p. These incidences of LOH were significantly higher than would be expected, since overall genetic instability in these HFAL tumours ranged from 14% to 45% LOH. Nine of the 14 patients in the LFAL group were found to have no LOH on 3p, 9p or 17p, but five of these had LOH at other sites: i.e. LOH on 5p, 5q, 8p, 13q, 16q and 19q. These results indicate that LFAL patients form a new subset of NSCLC tumours with distinct molecular-initating events, and may represent a discrete genetic population

The Ethical Triage and Management Guidelines of the Entrapped and Mangled Extremity in Resource Scarce Environments: A Systematic Literature Review.

ABSTRACTObjective:A systematic literature review (SLR) was performed to elucidate the current triage and treatment of an entrapped or mangled extremity in resource scarce environments (RSEs).Methods:A lead researcher followed the search strategy following inclusion and exclusion criteria. A first reviewer (FR) was randomly assigned sources. One of the 2 lead researchers was the second reviewer (SR). Each determined the level of evidence (LOE) and quality of evidence (QE) from each source. Any differing opinions between the FR and SR were discussed between them, and if differing opinions remained, then a third reviewer (the other lead researcher) discussed the article until a consensus was reached. The final opinion of each article was entered for analysis.Results:Fifty-eight (58) articles were entered into the final study. There was 1 study determined to be LOE 1, 29 LOE 2, and 28 LOE 3, with 15 determined to achieve QE 1, 37 QE 2, and 6 QE 3.Conclusion:This SLR showed that there is a lack of studies producing strong evidence to support the triage and treatment of the mangled extremity in RSE. Therefore, a Delphi process is suggested to adapt and modify current civilian and military triage and treatment guidelines to the RSE

Age-Related Changes in the Natural Killer Cell Response to Seasonal Influenza Vaccination Are Not Influenced by a Synbiotic: a Randomised Controlled Trial

Natural killer (NK) cells are an important component of the immune response to influenza infection, but are subject to alteration during aging, which may play a role in impaired response to infection and vaccination in older people. Enhancement of NK cell activity could, therefore, present a means to improve the immune response to vaccination in older subjects, and pre- and probiotics offer an opportunity to modulate antiviral defenses via alteration of the gut microbiota. This study investigated the effect of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52486, combined with a prebiotic, gluco-oligosaccharide (B. longum + Gl-OS), on the NK cell response to seasonal influenza vaccination in young and older subjects in a double-blind, randomized controlled trial. There were significant effects of aging on NK cell phenotype, the most notable of which were an increase in CD56dim cells, mainly reflected in the CD16+ subset, a decrease in CD56bright cells, mainly reflected in the CD16− subset, and greater expression of the immunosenescence marker, CD57, on NK cell subsets. However, these changes only partially translated to differences in NK cell activity, observed as trends toward reduced NK cell activity in older subjects when analyzed on a per cell basis. Influenza vaccination increased the proportion of CD56bright cells and decreased the proportion of CD56dim cells, in young, but not older subjects. Although NK cell activity in response to vaccination was not significantly different between the young and older subjects, low post-vaccination NK cell activity was associated with poor seroconversion in only the older subjects. There was no influence of the synbiotic on NK cell phenotype or activity, either before or after influenza vaccination. In conclusion, aging is associated with marked alteration of the phenotype of the NK cell population and there was evidence of an impaired NK cell response to influenza vaccination in older subjects. The effects of aging on NK cell phenotype and activity could not be offset by B. longum + Gl-OS

Impact of ageing and a synbiotic on the immune response to seasonal influenza vaccination; a randomised controlled trial

Background & aims Ageing increases risk of respiratory infections and impairs the response to influenza vaccination. Pre- and pro-biotics offer an opportunity to modulate anti-viral defenses and the response to vaccination via alteration of the gut microbiota. This study investigated the effect of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52486, combined with a prebiotic, gluco-oligosaccharide, on the B and T cell response to seasonal influenza vaccination in young and older subjects . Methods In a double-blind, randomized controlled trial, 58 young (18–35 y) and 54 older (60–85 y) subjects were supplemented with the synbiotic for 8 weeks. At 4 weeks they were administered with a seasonal influenza vaccine. B and T cell phenotype and responsiveness to in vitro re-stimulation with the vaccine were assessed at baseline, 4, 6 and 8 weeks. Results B and T cell profiles differed markedly between young and older subjects. Vaccination increased numbers of memory, IgA+ memory, IgG+ memory and total IgG+ B cells in young subjects, but failed to do so in older subjects and did not significantly alter T cell subsets. Seroconversion to the H1N1 subunit in the older subjects was associated with higher post-vaccination numbers of plasma B cells, but seroconversion was less consistently associated with T cell phenotype. B and T cell subsets from both young and older subjects demonstrated a strong antigen-specific recall challenge, and although not influenced by age, responsiveness to the recall challenge was associated with seroconversion. In older subjects, CMV seropositivity was associated with a significantly lower recall response to the vaccine, but the synbiotic did not affect the responsiveness of B or T cells to re-stimulation with influenza vaccine. Conclusions Antigen-specific B and T cell activation following an in vitro recall challenge with the influenza vaccine was influenced by CMV seropositivity, but not by a synbiotic

Impact of ageing and a synbiotic on the immune response to seasonal influenza vaccination; a randomised controlled trial

Background & Aims Ageing increases risk of respiratory infections and impairs the response to influenza vaccination. Pre- and probiotics offer an opportunity to modulate anti-viral defenses and the response to vaccination via alteration of the gut microbiota. This study investigated the effect of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52486, combined with a prebiotic, gluco-oligosaccharide, on the B and T cell response to seasonal influenza vaccination in young and older subjects. Methods In a double-blind, randomized controlled trial, 58 young (18-35y) and 54 older (60-85y) subjects were supplemented with the synbiotic for 8 weeks. At 4 weeks they were administered with a seasonal influenza vaccine. B and T cell phenotype and responsiveness to in vitro re-stimulation with the vaccine were assessed at baseline, 4, 6 and 8 weeks. Results B and T cell profiles differed markedly between young and older subjects. Vaccination increased numbers of memory, IgA+ memory, IgG+ memory and total IgG+ B cells in young subjects, but failed to do so in older subjects and did not significantly alter T cell subsets. Seroconversion to the H1N1 subunit in the older subjects was associated with higher post-vaccination numbers of plasma B cells, but seroconversion was less consistently associated with T cell phenotype. B and T cell subsets from both young and older subjects demonstrated a strong antigen-specific recall challenge, and although not influenced by age, responsiveness to the recall challenge was associated with seroconversion. In older subjects, CMV seropositivity was associated with a significantly lower recall response to the vaccine, but the synbiotic did not affect the responsiveness of B or T cells to re-stimulation with influenza vaccine. Conclusions Antigen-specific B and T cell activation following an in vitro recall challenge with the influenza vaccine was influenced by CMV seropositivity, but not by a synbiotic