Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 121
Filter
1.
J Hosp Infect ; 141: 152-166, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37696473

ABSTRACT

BACKGROUND: Hospital-acquired infections (HAIs) and infectious agents exhibiting antimicrobial resistance (AMR) are challenges globally. Environmental patient-facing wastewater apparatus including handwashing sinks, showers and toilets are increasingly identified as sources of infectious agents and AMR genes. AIM: To provide large-scale metagenomics analysis of wastewater systems in a large teaching hospital in the Republic of Ireland experiencing multi-drug-resistant HAI outbreaks. METHODS: Wastewater pipe sections (N=20) were removed immediately prior to refurbishment of a medical ward where HAIs had been endemic. These comprised toilet U-bends, and sink and shower drains. Following DNA extraction, each pipe section underwent metagenomic analysis. FINDINGS: Diverse taxonomic and resistome profiles were observed, with members of phyla Proteobacteria and Actinobacteria dominating (38.23 ± 5.68% and 15.78 ± 3.53%, respectively). Genomes of five clinical isolates were analysed. These AMR bacterial isolates were from patients >48 h post-admission to the ward. Genomic analysis determined that the isolates bore a high number of antimicrobial resistance genes (ARGs). CONCLUSION: Comparison of resistome profiles of isolates and wastewater metagenomes revealed high degrees of similarity, with many identical ARGs shared, suggesting probable acquisition post-admission. The highest numbers of ARGs observed were those encoding resistance to clinically significant and commonly used antibiotic classes. Average nucleotide identity analysis confirmed the presence of highly similar or identical genomes in clinical isolates and wastewater pipes. These unique large-scale analyses reinforce the need for regular cleaning and decontamination of patient-facing hospital wastewater pipes and effective infection control policies to prevent transmission of nosocomial infection and emergence of AMR within potential wastewater reservoirs.


Subject(s)
Biological Products , Cross Infection , Microbiota , Humans , Wastewater , Microbiota/genetics , Hospitals, Teaching , Anti-Bacterial Agents , Cross Infection/epidemiology , Genes, Bacterial
2.
J Hosp Infect ; 106(3): 522-535, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32800825

ABSTRACT

Breast cancer is the second most prevalent form of cancer in women worldwide, with surgery remaining the standard treatment. The adverse impact of the surgery remains controversial. It has been suggested that systemic factors during the postoperative period may increase the risk of recurrence, specifically surgical site infection (SSI). The aim of this review was to critically appraise current published literature regarding the influence of SSIs, after primary breast cancer surgery, on breast cancer recurrence, and to delve into potential links between these. This systematic review adopted two approaches: to identify the incidence rates and risk factors related to SSI after primary breast cancer surgery; and, secondly, to examine breast cancer recurrence following SSI occurrence. Ninety-nine studies with 484,605 patients were eligible in the SSI-focused searches, and 53 studies with 17,569 patients for recurrence-focused. There was a 13.07% mean incidence of SSI. Six-hundred and thirty-eight Gram-positive and 442 Gram-negative isolates were identified, with methicillin-susceptible Staphylococcus aureus and Escherichia coli most commonly identified. There were 2077 cases of recurrence (11.8%), with 563 cases of local recurrence, 1186 cases of distant and 25 cases which recurred both locally and distantly. Five studies investigated the association between SSI and breast cancer recurrence with three concluding that an association did exist. In conclusion, there is association between SSI and adverse cancer outcomes, but the cellular link between them remains elusive. Confounding factors of retrospective study design, surgery type and SSI definition make results challenging to compare and interpret. A standardized prospective study with appropriate statistical power is justified.


Subject(s)
Bacteria/isolation & purification , Breast Neoplasms/microbiology , Breast Neoplasms/surgery , Neoplasm Recurrence, Local/microbiology , Surgical Wound Infection/complications , Antibiotic Prophylaxis , Bacteria/classification , Female , Humans , Incidence , Prospective Studies , Retrospective Studies , Risk Factors , Surgical Wound Infection/microbiology
3.
Ann Biomed Eng ; 48(2): 582-594, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31555984

ABSTRACT

Wall shear stress (WSS) is an important stimulus in vascular remodelling and vascular lesion development. The current methods to assess and predict the risk associated with specific unsteady WSS consider the WSS mean values or the presence of reverse phases described by the oscillatory shear index. Recent evidence has shown that the accuracy of these methods is limited, especially with respect to the venous environment. Unsteady WSS are characterised by several features that may individually affect endothelial cells. Consequently, we assessed the effects of averaged WSS (TAWSS), temporal WSS gradient (TWSSG), maximum WSS (WSS peak) and reverse phase (OSI) by applying different WSS profiles to venous EC in-vitro, using a real-time controlled cone-and-plate cell-shearing device for 24 h. We found that TWSSG and WSS peak affect cell elongation and alignment respectively. We also found that the WSS waveforms with a peak of 1.5 Pa or higher significantly correlate with the induction of a protective phenotype. Cell phenotype induced by these high peak waveforms does not correlate to what is predicted by the hemodynamic indices currently used. The definition of reliable hemodynamic indices can be used to inform the computational models aimed at estimating the hemodynamic effects on vascular remodelling.


Subject(s)
Hemodynamics , Human Umbilical Vein Endothelial Cells/metabolism , Models, Cardiovascular , Shear Strength , Stress, Mechanical , Human Umbilical Vein Endothelial Cells/cytology , Humans
4.
J Child Orthop ; 13(3): 304-309, 2019 Jun 01.
Article in English | MEDLINE | ID: mdl-31312270

ABSTRACT

PURPOSE: Scoliosis is a condition of abnormal growth resulting in 3D deformity of both the spine and thoracic cage. The aim of this study is to use chest radiographs of healthy children to define normal thoracic proportions so as to provide a useful normal reference range against which children with spinal deformity can be compared. METHODS: Three independent reviewers assessed posteroanterior and lateral chest radiographs of 184 normal children aged between two and 15 years. Duplicate assessments were undertaken by all three raters on 36 of these radiographs. We measured the T1 to T12 length, sternal length, chest depth at T6, chest width at T3, chest width at T6 and maximum chest width. Ratios of thoracic dimensions were calculated to define the normal proportions of the thorax. Inter- and intra-rater variance was estimated for all dimensions and dimension ratios. RESULTS: The intra-rater and inter-rater reliability was excellent with intra-class-correlation coefficients values > 80% and both intra- and inter-rater coefficients of variance < 9% for all parameters. All measured dimensions of the thorax and spine progressed linearly with respect to age. The mean proportions of T1 to 12 length of the sternal length, chest depth at T6, chest width at T3, chest width at T6 and maximum chest width were 0.5, 0.4, 0.7, 0.9 and 1.0, respectively. CONCLUSION: It is possible to accurately and reproducibly measure the dimensions of the thoracic cage and spine on plain film radiology. The ratios of T1 to T12 length with respect to sternal length, chest depth at T6, chest width at T3, chest width at T6 and maximum chest remain constant with increasing age. Thoracic dimensions in children progress linearly with increasing age. LEVEL OF EVIDENCE: V.

5.
J R Coll Physicians Edinb ; 48(3): 233-238, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30191911

ABSTRACT

Genetic haemochromatosis is an autosomal recessive disorder, mostly due to HFE gene mutation, leading to loss of hepcidin and unregulated iron loading. The consequences include hepatic fibrosis, cardiomyopathy and skin pigmentation, and these sequelae along with fatigue may be prevented by 'de-ironing'. Joint pain is frequently reported at diagnosis and an arthropathy that is essentially accelerated osteoarthritis may develop, with onset at a younger than expected age, involvement of typical and atypical joints, such as metacarpophalangeal and ankle, exuberant osteophytes and rapid progression to cartilage loss and the need for arthroplasty. The arthropathy differs from the other features in not responding to de-ironing, new joints becoming affected once patients are in maintenance, and, intriguingly, classic cases occur in the absence of iron overload with major and minor HFE mutations. These anomalies present a conundrum that raise the question whether HFE mutations have an arthritogenic consequence independent of hepcidin and iron.


Subject(s)
Hemochromatosis Protein/genetics , Hemochromatosis/complications , Hemochromatosis/genetics , Osteoarthritis/genetics , Genotype , Hemochromatosis/drug therapy , Humans , Osteoarthritis/diagnostic imaging , Phenotype
6.
Clin Radiol ; 73(3): 323.e1-323.e8, 2018 03.
Article in English | MEDLINE | ID: mdl-29126545

ABSTRACT

AIM: To examine the magnetic resonance imaging (MRI) features of the ankle and subtalar joints that might distinguish genetic haemochromatosis (GH). MATERIALS AND METHODS: The present study was a retrospective case-control study comparing 30 MRI studies of GH patients with ankle or subtalar arthropathy with 30 matched controls with ankle pain. Anonymised images were scored using a semi-quantative tool adapted from the MRI osteoarthritis knee score. Scores were generated for bone marrow lesions size, number, and distinguishing the proportion of each lesion consisting of subchondral cyst versus oedema. Articular cartilage loss and osteophytes were documented. The primary comparator was bone marrow lesion size. Paired Student's t-test and the chi-squared test were utilised to compare outcomes. RESULTS: Bone marrow lesion/cyst size and number, presence and extent of full-thickness cartilage loss, and osteophyte scores were significantly higher in ankle joints of GH cases (p<0.01). In the middle subtalar articulation, there were significantly higher scores for full-thickness cartilage loss and extent and osteophytes in GH cases (p<0.05). There were no significant differences in the posterior subtalar articulation. CONCLUSION: The finding of both numerous and large cysts on ankle MRI should raise suspicion of GH. Other MRI features of potential diagnostic value include large osteophytes and the presence of extensive full-thickness cartilage loss in the ankle joint and middle subtalar articulation.


Subject(s)
Ankle Joint/diagnostic imaging , Hemochromatosis/diagnostic imaging , Magnetic Resonance Imaging/methods , Subtalar Joint/diagnostic imaging , Adult , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Pain Measurement , Retrospective Studies
7.
Vox Sang ; 112(7): 614-621, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28833229

ABSTRACT

BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) is a known transfusion-transmissible agent. HEV infection has increased in prevalence in many developed nations with RNA detection in donors as high as 1 in 600. A high proportion of HEV infections are asymptomatic and therefore not interdicted by donor exclusion criteria. To manage the HEV transfusion-transmission (TT) risk some developed nations have implemented HEV RNA screening. In Australia, HEV is rarely notified; although locally acquired infections have been reported, and the burden of disease is unknown. The purpose of this study was to determine the frequency of HEV infection in Australian donors and associated TT risk. MATERIALS AND METHODS: Plasma samples (n = 74 131) were collected from whole blood donors during 2016 and screened for HEV RNA by transcription-mediated amplification (TMA) in pools of six. Individual TMA reactive samples were confirmed by RT-PCR and, if positive, viral load determined. Prevalence data from the study were used to model the HEV-TT risk. RESULTS: One sample in 74 131 (95% CI: 1 in 1 481 781 to 1 in 15 031) was confirmed positive for HEV RNA, with an estimated viral load of 180 IU/ml, which is below that typically associated with TT. Using a transmission-risk model, we estimated the risk of an adverse outcome associated with TT-HEV of approximately 1 in 3·5 million components transfused. CONCLUSION: Hepatitis E virus viremia is rare in Australia and lower than the published RNA prevalence estimates of other developed countries. The risk of TT-HEV adverse outcomes is negligible, and HEV RNA donor screening is not currently indicated.


Subject(s)
Blood Donors , Hepatitis E virus/genetics , Hepatitis E/epidemiology , RNA, Viral/blood , Australia , Hepatitis E/blood , Hepatitis E virus/isolation & purification , Humans , Male , Middle Aged , Prevalence , Risk Assessment
8.
Vox Sang ; 112(6): 542-548, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28850195

ABSTRACT

BACKGROUND AND OBJECTIVE: The significance of anti-HCV immunoblot (IB) indeterminate results can be difficult to determine. We analysed results for blood donors tested on the MP Diagnostics HCV Blot 3.0 IB assay to determine whether indeterminate results representing past exposure to HCV could be distinguished from those due to non-specific reactivity. MATERIALS AND METHODS: Results for all donors tested by IB during the study period (July 2010 to December 2013) were included in this study. RESULTS: Of 131 donors tested by IB, 34 (26.0%) were negative, 38 (29.0%) were indeterminate, and 59 (45.0%) were positive. There was no significant difference in IB band reactivity strength between indeterminate and positive donors. The PRISM HCV chemiluminescent immunoassay (ChLIA) sample to cut-off (s/co) ratio distribution for the indeterminate donors was significantly higher than for those with biological false reactivity (P = 0·037), but significantly lower than for donors who were IB positive/HCV RNA negative (P < 0·001) or IB not tested/HCV RNA positive (P < 0·001). Of donors available for follow-up, 53.1% of the indeterminate group disclosed a putative risk factor for HCV infection compared to 39.4% (P < 0·001) for the IB-negative group, 76.6% (P = 0·065) for the IB-positive group and 83.4% (P < 0·001) for the HCV RNA-positive group. CONCLUSION: The results of this study indicate that PRISM ChLIA s/co ratios >2·00 with IB indeterminate results predict exposure to HCV, particularly in the presence of putative risk factors for HCV infection. These findings may be applied to optimizing counselling of donors with indeterminate HCV results.


Subject(s)
Blood Donors , Hepatitis C Antibodies/blood , Hepatitis C/diagnosis , Immunoblotting , RNA, Viral/blood , Blood Safety , Hepacivirus/immunology , Humans , Risk Factors
10.
Bioresour Technol ; 238: 633-642, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28486196

ABSTRACT

The manual manometric biochemical methane potential (mBMP) test uses the increase in pressure to calculate the gas produced. This gas production may be affected by the headspace volume in the incubation bottle and by the overhead pressure measurement and release (OHPMR) frequency. The biogas and methane yields of cellulose, barley, silage and slurry were compared with three incubation bottle headspace volumes (50, 90 and 180ml; constant 70ml total medium) and four OHPMR frequencies (daily, each third day, weekly and solely at the end of experiment). The methane yields of barley, silage and slurry were compared with those from an automated volumetric method (AMPTS). Headspace volume and OHPMR frequency effects on biogas yield were mediated mainly through headspace pressure, with the latter having a negative effect on the biogas yield measured and relatively little effect on methane yield. Two mBMP treatments produced methane yields equivalent to AMPTS.


Subject(s)
Biofuels , Methane , Pressure , Silage
11.
J Appl Microbiol ; 122(5): 1197-1206, 2017 May.
Article in English | MEDLINE | ID: mdl-28245080

ABSTRACT

AIMS: Silage is grass, preserved by fermentation and used as winter feed for cattle. The impact of a range of current grass silage preparation practices on the survival of Escherichia coli C600φ3538(Δvtx2 ::cat) and on the induction, release and infectivity of free phage were investigated. METHODS AND RESULTS: Wilted and fresh grass samples, from plots with and without slurry application, were ensiled with or without formic acid. Each treatment combination was inoculated with approximately 6 log10 CFU per g E. coli C600φ3538(Δvtx2 ::cat) (donor strain) and E. coli C600::kanamycinR (recipient strain) in test-tube model silos and incubated in the dark at 15°C. The physico-chemical (pH, ammonia, ethanol, lactic acid and volatile fatty acids) and microbiological (total viable counts, TVC, total Enterobacteriaceae counts, TEC, E. coli counts, ECC and lactic acid bacteria, LAB) properties of each fermentation were monitored throughout the experiment as were the concentrations of E. coli C600φ3538(Δvtx2 ::cat), E. coli C600::kanamycinR , free phage and transductants, using culture and PCR-based methods. Over the course of the experiment the pH of the grass samples typically decreased by 2 pH units. TVC, TEC and ECC decreased by up to 2·3, 6·4 and 6·2 log10 CFU per g, respectively, while the LAB counts remained relatively stable at 5·2-7·1 log10 CFU per g. Both donor and recipient strains decreased by approximately 5 log10 CFU per g. Free phages were detected in all treatments and transductants were detected and confirmed by PCR in the silo containing wilted grass, pretreated with slurry and ensiled without formic acid. CONCLUSIONS: Verocytotoxigenic E. coli may survive the ensiling process and the conditions encountered are sufficient to induce vtx2 bacteriophage leading to low levels of phage-mediated vtx2 gene transfer. SIGNIFICANCE AND IMPACT OF THE STUDY: These studies suggest that the ensiling of grass may create an environment which facilitates the emergence of new verocytotoxigenic E. coli.


Subject(s)
Escherichia coli/isolation & purification , Poaceae/microbiology , Poaceae/virology , Prophages/isolation & purification , Silage/microbiology , Silage/virology , Animal Feed/analysis , Animal Feed/microbiology , Animal Feed/virology , Animals , Cattle , Escherichia coli/genetics , Escherichia coli/growth & development , Escherichia coli/metabolism , Fatty Acids, Volatile/metabolism , Fermentation , Food Handling , Formates/metabolism , Hydrogen-Ion Concentration , Lactic Acid/metabolism , Prophages/genetics , Prophages/growth & development , Prophages/metabolism , Silage/analysis
12.
Eur Spine J ; 26(2): 336-344, 2017 02.
Article in English | MEDLINE | ID: mdl-26873103

ABSTRACT

BACKGROUND: Steroids in transforaminal epidural injections are widely used to ease radicular pain in both cervical and lumbar radiculopathy. Concerns have been articulated about the use of particulate steroids for this intervention, as a number of case reports have been published linking them with post procedural paralysis, possibly due to spinal ischaemia secondary to a steroid particulate embolism. Non-particulate, or soluble steroids, are mooted as an alternative; however, their effectiveness relative to particulate steroids has not been conclusively proven. STUDY DESIGN: We review the evidence in the published literature regarding the efficacy of non-particulate steroids in epidural injections compared to particulate steroids, and synthesise it to gauge the qualitative outcomes from level one evidence (visual analogue scales, numerical pain scores and Oswestry Disability Index) from baseline to specified follow up. METHODS: The PRISMA guidelines were utilised for this review. An internet search was performed to collate the available literature from medical databases PubMed, EMBASE, Web of Science and the Cochrane library. We used a broad search term [epidural (and) steroid] to ensure a wide capture of articles. No limitations in terms of language or date of publication were implemented. The reference lists of articles included for full text review were searched for any additional primary or review publications. RESULTS: Four online libraries were searched, with a combined total of 11,353 titles reviewed, not excluding duplicates. Post title abstract and full text review, nine articles were identified as suitable for inclusion for qualitative synthesis. Four of these were suitable for quantitative synthesis, with a total of 300 participants, 147 in the particulate group and 153 in the non-particulate group. Using a random effects model, the pooled standard mean difference of VAS score diminution was not significant between groups (0.31 in favour of particulates, 95 % CI -0.68 to 1.30). From our qualitative synthesis, there was a trend for greater improvement in pain scores within the particulate group. The type of steroid used did not appear to have an effect on the disability score given by patients. CONCLUSION: Particulate steroids are not demonstrably better in relieving pain compared to their non-particulate counterparts. In view of the concerns over the safety profile of particulate steroids, it may be prudent to switch to non particulates, or at the very least the dangers and alternatives should be flagged with the patient group as part of a shared decision making process.


Subject(s)
Glucocorticoids/therapeutic use , Injections, Epidural , Radiculopathy/drug therapy , Disability Evaluation , Humans , Pain Measurement
13.
Vox Sang ; 112(1): 3-8, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27564651

ABSTRACT

BACKGROUND AND OBJECTIVES: We previously published a model to estimate the residual risk (RR) for occult hepatitis B infection (OBI) in the absence of universal anti-HBc testing. To incorporate new information on the epidemiology of OBI, we describe model refinements and estimate a more accurate HBV RR due to OBI in Australia. MATERIALS AND METHODS: In our original model, the OBI risk, p(OBI), was defined by the rate of 'non-detection' by the HBV DNA screening test in use, p(NAT non-detection), and the average infectivity of blood components from OBI donors, p(transmission). We revised the model by integrating three refinements: that donations with anti-HBs levels of >10 IU/l, or donations solely for manufactured plasma products, be excluded from the risk calculation, and an updated estimate of p(transmission). RESULTS: Refining our OBI RR model resulted in a more than 10-fold reduction in the reported RR risk to recipients from OBI in our donor population. Based on the use of a common data set, the mean OBI RR risk decreased from 1 in 374 354 donations (95% CI: 1 in 191 940-1 072 681) to 1 in 3 984 033 (95% CI: 1 in 1 146 188-65 268 257) for the refined model. CONCLUSION: Our model refinements provide a more realistic measure of the HBV RR in the donor population. Unlike the previous model, the new model demonstrates that the risk of HBV due to OBI in the Australian blood donor population is negligible, and further potentially cost-ineffective risk management strategies are not currently warranted.


Subject(s)
Blood Transfusion , Hepatitis B/transmission , Models, Theoretical , Blood Donors , DNA, Viral/blood , Hepatitis B/epidemiology , Hepatitis B/virology , Hepatitis B Antibodies/blood , Hepatitis B Core Antigens/immunology , Hepatitis B virus/genetics , Hepatitis B virus/isolation & purification , Humans , Oligonucleotide Array Sequence Analysis , Risk
14.
Int J Cancer ; 140(1): 234-246, 2017 Jan 01.
Article in English | MEDLINE | ID: mdl-27615392

ABSTRACT

The identification and validation of a targeted therapy for patients with triple-negative breast cancer (TNBC) is currently one of the most urgent needs in breast cancer therapeutics. One of the key reasons for the failure to develop a new therapy for this subgroup of breast cancer patients has been the difficulty in identifying a highly prevalent, targetable molecular alteration in these tumors. Recently however, the p53 gene was found to be mutated in approximately 80% of basal/TNBC, raising the possibility that targeting the mutant p53 protein product might be a new approach for the treatment of this form of breast cancer. In this study, we investigated the anti-cancer activity of PRIMA-1 and PRIMA-1MET (APR-246), two compounds which were previously reported to reactivate mutant p53 and convert it to a form with wild-type (WT) properties. Using a panel of 18 breast cancer cell lines and 2 immortalized breast cell lines, inhibition of proliferation by PRIMA-1 and PRIMA-1MET was found to be cell-line dependent, but independent of cell line molecular subtype. Although response was independent of molecular subtype, p53 mutated cell lines were significantly more sensitive to PRIMA-1MET than p53 WT cells (p = 0.029). Furthermore, response (measured as IC50 value) correlated significantly with p53 protein level as measured by ELISA (p = 0.0089, r=-0.57, n = 19). In addition to inhibiting cell proliferation, PRIMA-1MET induced apoptosis and inhibited migration in a p53 mutant-dependent manner. Based on our data, we conclude that targeting mutant p53 with PRIMA-1MET is a potential new approach for treating p53-mutated breast cancer, including the subgroup with triple-negative (TN) disease.


Subject(s)
Aza Compounds/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Mutation , Quinuclidines/pharmacology , Triple Negative Breast Neoplasms/genetics , Tumor Suppressor Protein p53/genetics , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Molecular Targeted Therapy , Mutation/drug effects , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/metabolism , Tumor Suppressor Protein p53/metabolism
15.
Scand J Rheumatol ; 46(1): 69-74, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27187562

ABSTRACT

OBJECTIVES: To examine demographic and clinical features leading to the diagnosis of hereditary haemochromatosis and assess factors that might enhance earlier diagnosis, with particular attention to arthritic symptoms. METHOD: Diagnostic features were captured directly from patients with haemochromatosis attending a specialist rheumatology clinic (group 1) and from analysis of a specifically designed questionnaire circulated to members of the UK Haemochromatosis Society (group 2). RESULTS: In groups 1 (n = 62) and 2 (n = 470), respectively, the diagnosis of haemochromatosis was made at a mean age of 52.8 and 56.4 years with 77% and 76% reporting joint symptoms with a mean duration of 8.3 and 8.1 years. The first joints to be affected in group 1 were the metacarpophalangeal (MCP; 38.5%) and ankle (29.5%) followed by the knee, hip, and proximal interphalangeal (PIP) joints. At the time of clinical assessment or questionnaire completion, the most prevalent regions with arthropathy in group 1 were PIP (64.5%), knee (64%), ankle (61%), and MCP (60%) and in group 2 the most prevalent joint regions self-reported were the first carpometacarpal (CMC; 59%), wrist (52%), PIP (47%), MCP (46%), knee (42%), and ankle (35%). CONCLUSIONS: Data from both cohorts confirm the high prevalence of joint symptoms in haemochromatosis predating the diagnosis by many years. Discriminatory features of the arthropathy include the involvement of MCP joints and ankles at a relatively young age in the absence of trauma, all of which are unusual features of primary osteoarthritis (OA). The finding of this presentation should prompt diagnostic tests for haemochromatosis.


Subject(s)
Hemochromatosis/diagnosis , Hemochromatosis/epidemiology , Joint Diseases/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Ankle Joint , Cohort Studies , Female , Hemochromatosis/complications , Hemochromatosis/genetics , Humans , Male , Metacarpophalangeal Joint , Middle Aged , United Kingdom/epidemiology , Young Adult
16.
Oncogene ; 35(40): 5272-5281, 2016 10 06.
Article in English | MEDLINE | ID: mdl-26996668

ABSTRACT

C/EBPα (p42 and p30 isoforms) is commonly dysregulated in cancer via the action of oncogenes, and specifically in acute myeloid leukaemia (AML) by mutation. Elevated TRIB2 leads to the degradation of C/EBPα p42, leaving p30 intact in AML. Whether this relationship is a cooperative event in AML transformation is not known and the molecular mechanism involved remains elusive. Using mouse genetics, our data reveal that in the complete absence of C/EBPα, TRIB2 was unable to induce AML. Only in the presence of C/EBPα p42 and p30, were TRIB2 and p30 able to cooperate to decrease the latency of disease. We demonstrate that the molecular mechanism involved in the degradation of C/EBPα p42 requires site-specific direct interaction between TRIB2 and C/EBPα p42 for the K48-specific ubiquitin-dependent proteasomal degradation of C/EBPα p42. This interaction and ubiquitination is dependent on a critical C terminal lysine residue on C/EBPα. We show effective targeting of this pathway pharmacologically using proteasome inhibitors in TRIB2-positive AML cells. Together, our data show that excess p30 cooperated with TRIB2 only in the presence of p42 to accelerate AML, and the direct interaction and degradation of C/EBPα p42 is required for TRIB2-mediated AML.


Subject(s)
CCAAT-Enhancer-Binding Protein-alpha/genetics , Calcium-Calmodulin-Dependent Protein Kinases/genetics , Intracellular Signaling Peptides and Proteins/genetics , Leukemia, Myeloid, Acute/genetics , Protein Isoforms/genetics , Animals , CCAAT-Enhancer-Binding Protein-alpha/antagonists & inhibitors , Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Humans , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/pathology , Mice , Mutation , Proteasome Inhibitors/administration & dosage , Protein Isoforms/biosynthesis
17.
Vox Sang ; 110(4): 317-23, 2016 May.
Article in English | MEDLINE | ID: mdl-26748600

ABSTRACT

BACKGROUND AND OBJECTIVES: Ross River virus (RRV) is an enveloped, RNA alphavirus in the same antigenic group as chikungunya virus. Australia records an annual average of 5000 laboratory-confirmed RRV infections. While RRV is currently geographically restricted to the Western Pacific, the capacity of arboviruses for rapid expansion is well established. The first case of RRV transfusion-transmission was recently described prompting a comprehensive risk assessment. MATERIALS AND METHODS: To estimate the RRV residual risk, we applied laboratory-confirmed RRV notifications to two published models. This modelling generated point estimates for the risk of viraemia in the donor population, the risk of collecting a viraemic donation and the predicted number of infected components. RESULTS: The EUFRAT model estimated the risk of infection in donors as one in 95 039 (one in 311 328 to one in 32 399) to one in 14 943 (one in 48 593 to one in 5094). The point estimate for collecting a RRV viraemic donation varied from one in 166 486 (one in 659 078 to one in 49 158) (annualized national risk) to one in 26 117 (one in 103 628 to one in 7729) (area of high transmission). The modelling predicted 8-11 RRV-infected labile blood components issued in Australia during a 1-year period. CONCLUSION: Considering the uncertainty in the modelled estimates, the unknown rate of RRV donor viraemia and the low severity of any recipient RRV infection, additional risk management for RRV in Australia will initially be restricted to strengthening the messaging to donors regarding prompt reporting of any postdonation illnesses.


Subject(s)
Alphavirus Infections/transmission , Ross River virus/isolation & purification , Alphavirus Infections/epidemiology , Alphavirus Infections/virology , Australia/epidemiology , Blood Donors , Blood Transfusion , Humans , Risk Assessment
18.
Ir J Med Sci ; 185(2): 463-71, 2016 May.
Article in English | MEDLINE | ID: mdl-26742534

ABSTRACT

BACKGROUND: Surgical procedures to correct larger curve magnitudes >70° in patients with adolescent idiopathic scoliosis (AIS) are still common; despite their increased complexity, limited research has assessed the effect of preoperative curve severity on outcomes. AIM: This study aimed to examine the impact of preoperative curves >70° vs. those ≤70° on perioperative, functional and financial outcomes in patients with AIS undergoing posterior spinal fusion (PSF). METHODS: Seventy seven eligible AIS patients who underwent PSF were prospectively followed-up, until return to preoperative function was reported. Preoperative curves >70° vs. ≤70° were analysed in relation to surgical duration, estimated blood loss, perioperative complications, length of hospitalisation, return to function and cost of surgical treatment per patient. RESULTS: Severe preoperative curves >70°, identified in 21 patients (27.3 %), were associated with significantly longer surgical duration (median 6.5 vs. 5 h, p = 0.001) and increased blood loss (median 1250 vs. 1000 ml, p = 0.005)-these patients were 2.1 times more likely to receive a perioperative blood product transfusion (Relative Risk 2.1, CI 1.4-2.7, p = 0.004). Curves >70° were also associated with a significantly delayed return to school/college, and an increased cost of surgical treatment (€33,730 vs. €28,620, p < 0.0001). CONCLUSION: Surgeons can expect a longer surgical duration, greater intraoperative blood loss and double the blood product transfusion risk when performing PSF procedures on AIS patients with curves greater than 70° vs. those ≤70°. Surgical correction for curves >70°, often as a result of lengthy surgical waiting lists, also incurs added expense and results in a partial delay in early functional recovery.


Subject(s)
Blood Loss, Surgical , Scoliosis/surgery , Spinal Fusion/methods , Adolescent , Blood Transfusion , Female , Humans , Male , Prospective Studies , Time Factors , Treatment Outcome
19.
Ir J Med Sci ; 185(2): 513-20, 2016 May.
Article in English | MEDLINE | ID: mdl-25935207

ABSTRACT

BACKGROUND: Posterior spinal instrumentation and fusion for correction of adolescent idiopathic scoliosis (AIS) typically requires lengthy operating time and may be associated with significant blood loss and subsequent transfusion. This study aimed to identify factors predictive of duration of surgery, intraoperative blood loss and transfusion requirements in an Irish AIS cohort. METHODS: A retrospective review of 77 consecutive patients with AIS who underwent single-stage posterior spinal instrumentation and fusion over a two-year period at two Dublin tertiary hospitals was performed. Data were collected prospectively and parameters under analysis included pre- and postoperative radiographic measurements, intraoperative blood loss, surgical duration, blood products required, laboratory blood values and perioperative complications. RESULTS: Mean preoperative primary curve Cobb angle was 62.3°; mean surgical duration was 5.6 h. The perioperative allogeneic red blood cell transfusion rate was 42.8 % with a median requirement of 1 unit. Larger curve magnitudes were positively correlated with longer fusion segments, increased operative time and greater estimated intraoperative blood loss. Preoperative Cobb angles greater than 70° [Relative Risk (RR) 4.42, p = 0.003] and estimated intraoperative blood loss greater than 1400 ml (RR 3.01, p = 0.037) were independent predictors of red blood cell transfusion risk. CONCLUSION: Larger preoperative curve magnitudes in AIS increase operative time and intraoperative blood loss; preoperative Cobb angles greater than 70(o) and intraoperative blood loss greater than 1400 ml are predictive of red blood cell transfusion requirement in this patient group.


Subject(s)
Blood Loss, Surgical , Blood Transfusion , Scoliosis/surgery , Spinal Fusion/methods , Adolescent , Female , Humans , Male , Neurosurgical Procedures/methods , Operative Time , Retrospective Studies , Treatment Outcome
20.
Bioresour Technol ; 192: 266-71, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26038332

ABSTRACT

This work examines the digestion of advanced growth stage grass silage. Two variables were investigated: particle size (greater than 3 cm and less than 1cm) and rumen fluid addition. Batch studies indicated particle size and rumen fluid addition had little effect on specific methane yields (SMYs). In continuous digestion of 3 cm silage the SMY was 342 and 343 L CH4 kg(-1)VS, respectively, with and without rumen fluid addition. However, digester operation was significantly affected through silage floating on the liquor surface and its entanglement in the mixing system. Digestion of 1cm silage with no rumen fluid addition struggled; volatile fatty acid concentrations rose and SMYs dropped. The best case was 1cm silage with rumen fluid addition, offering higher SMYs of 371 L CH4 kg(-1)VS and stable operation throughout. Thus, physical and biological treatments benefited continuous digestion of high fibre grass silage.


Subject(s)
Lignin/chemistry , Methane/chemistry , Poaceae/chemistry , Rumen/chemistry , Animals , Fatty Acids, Volatile/chemistry , Particle Size , Silage
SELECTION OF CITATIONS
SEARCH DETAIL
...