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1.
Ir J Med Sci ; 189(4): 1435-1443, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32185749

ABSTRACT

BACKGROUND: Falling from a height of under 2 m (low fall) is the most common mechanism of injury causing major trauma in Ireland. This presentation encompasses a wide patient cohort, from paediatric sport injuries to elderly falls. AIMS: Our aim is to characterise major trauma resulting from a low fall, and its various sub-populations, to identify preventative strategies and care pathways to improve outcomes for patients. METHODS: The Trauma Audit and Research Network (TARN) which is used to provide Major Trauma Audit was used to retrospectively identify patients presenting to the Cork University Hospital Emergency Department with trauma resulting from a low fall from January 2015 to June 2018. RESULTS: The database returned 1066 qualifying cases (49.3% of cases in the time period), with a mean age of 67.3 years (SD = 21) and a median age of 71.3 years (IQR = 23); 44% were male. 'Mechanical falls' accounted for n = 513 (48%) of low-fall injuries, followed by 'stationary falls' n = 265 (25%). Injuries occurred most often at home n = 515 (48%), followed by public places n = 208 (19.5%). The most severely injured body region was the limbs n = 526 (49.3%), followed by the head n = 253 (23.7%). A number of patients with Glasgow Outcome Scores of 4 (moderate disability) and 5 (good recovery) were n = 488 (45.8%) and n = 390 (36.6%). CONCLUSIONS: Low falls occur in patients over 55 years of age; many do not return to independent living. Wait times to initial assessment, length of hospital stay and mortality increase with age. Mechanical falls at home are the most common cause of low-fall major trauma.


Subject(s)
Accidental Falls/statistics & numerical data , Wounds and Injuries/etiology , Adolescent , Adult , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
2.
ISME J ; 11(1): 15-30, 2017 01.
Article in English | MEDLINE | ID: mdl-27648810

ABSTRACT

Dysbiosis resulting in gut-microbiome alterations with reduced butyrate production are thought to disrupt intestinal immune homeostasis and promote complex immune disorders. However, whether and how dysbiosis develops before the onset of overt pathology remains poorly defined. Interleukin-15 (IL-15) is upregulated in distressed tissue and its overexpression is thought to predispose susceptible individuals to and have a role in the pathogenesis of celiac disease and inflammatory bowel disease (IBD). Although the immunological roles of IL-15 have been largely studied, its potential impact on the microbiota remains unexplored. Analysis of 16S ribosomal RNA-based inventories of bacterial communities in mice overexpressing IL-15 in the intestinal epithelium (villin-IL-15 transgenic (v-IL-15tg) mice) shows distinct changes in the composition of the intestinal bacteria. Although some alterations are specific to individual intestinal compartments, others are found across the ileum, cecum and feces. In particular, IL-15 overexpression restructures the composition of the microbiota with a decrease in butyrate-producing bacteria that is associated with a reduction in luminal butyrate levels across all intestinal compartments. Fecal microbiota transplant experiments of wild-type and v-IL-15tg microbiota into germ-free mice further indicate that diminishing butyrate concentration observed in the intestinal lumen of v-IL-15tg mice is the result of intrinsic alterations in the microbiota induced by IL-15. This reconfiguration of the microbiota is associated with increased susceptibility to dextran sodium sulfate-induced colitis. Altogether, this study reveals that IL-15 impacts butyrate-producing bacteria and lowers butyrate levels in the absence of overt pathology, which represent events that precede and promote intestinal inflammatory diseases.


Subject(s)
Bacteria/metabolism , Butyrates/metabolism , Colitis/metabolism , Dysbiosis/microbiology , Gastrointestinal Microbiome , Interleukin-15/metabolism , Intestines/microbiology , Animals , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Colitis/genetics , Colitis/microbiology , Colitis/therapy , Disease Susceptibility , Dysbiosis/genetics , Dysbiosis/metabolism , Fecal Microbiota Transplantation , Feces/microbiology , Female , Germ-Free Life , Humans , Interleukin-15/genetics , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Male , Mice , Mice, Inbred C57BL
3.
J Exp Med ; 212(10): 1487-95, 2015 Sep 21.
Article in English | MEDLINE | ID: mdl-26304964

ABSTRACT

Eicosanoids are inflammatory mediators that play a key but incompletely understood role in linking the innate and adaptive immune systems. Here, we show that cytotoxic effector T cells (CTLs) are capable of both producing and responding to cysteinyl leukotrienes (CystLTs), allowing for the killing of target cells in a T cell receptor-independent manner. This process is dependent on the natural killer receptor NKG2D and exposure to IL-15, a cytokine induced in distressed tissues. IL-15 and NKG2D signaling drives the up-regulation of key enzymes implicated in the synthesis of CystLTs, as well as the expression of CystLT receptors, suggesting a positive feedback loop. Finally, although the CystLT pathway has been previously linked to various allergic disorders, we provide unexpected evidence for its involvement in the pathogenesis of celiac disease (CD), a T helper 1 cell-mediated enteropathy induced by gluten. These findings provide new insights into the cytolytic signaling pathway of NKG2D and the pathogenesis of organ-specific immune disorders. Furthermore, they suggest that the blockade of CystLT receptors may represent a potent therapeutic target for CD or potentially other autoimmune disorders in which NKG2D has been implicated.


Subject(s)
Celiac Disease/immunology , Cysteine/metabolism , Interleukin-15/immunology , Leukotrienes/metabolism , NK Cell Lectin-Like Receptor Subfamily K/immunology , T-Lymphocytes, Cytotoxic/immunology , Adult , Arachidonate 5-Lipoxygenase/genetics , Arachidonate 5-Lipoxygenase/metabolism , Case-Control Studies , Celiac Disease/physiopathology , Cells, Cultured , Cysteine/immunology , Female , Humans , Interleukin-15/metabolism , Leukotrienes/immunology , Male , NK Cell Lectin-Like Receptor Subfamily K/metabolism , Receptors, Leukotriene/genetics , Receptors, Leukotriene/metabolism , Th1 Cells/immunology , Th1 Cells/metabolism , Up-Regulation
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