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1.
Crit Care Res Pract ; 2023: 4037915, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37720488

RESUMO

Introduction: Fungal infection is a cause of increased morbidity and mortality in intensive care patients. Critically unwell patients are at increased risk of developing invasive fungal infections. COVID-19 patients in the intensive care unit (ICU) may be at a particularly high risk. The primary aim of this study was to establish the incidence of secondary fungal infections in patients admitted to the ICU with COVID-19. Secondary aims were to investigate factors that may contribute to an increased risk of fungal infections and to calculate the mortality between fungal and nonfungal groups. Methods: We undertook a retrospective observational study in a tertiary ICU in Wales, United Kingdom. 174 patients admitted with COVID-19 infection from March 2020 until May 2021 were included. Data were collected through a retrospective review of patient's clinical notes and microbiology investigation results obtained from the online clinical portal. Results: 81/174 (47%) COVID-19 patients developed fungal infections, 93% of which were Candida species, including Candida albicans (88%), and 6% had an Aspergillus infection. Age and smoking history did not appear to be contributing factors. The nonfungal group had a significantly higher body mass index (33 ± 8 vs. 31 ± 7, p=0.01). The ICU length of stay (23 (1-116) vs. 8 (1-60), p < 0.001), hospital length of stay (30 (3-183) vs. 15 (1-174) ± 7, p < 0.001), steroid days (10 (1-116) vs. 4 (0-28), p=0.02), and ventilation days (18 (0-120) vs. 2 (0-55), p < 0.001) were significantly higher in the fungal group. The mortality rate in both groups was similar (51% vs. 52%). The Kaplan-Meier survival analysis showed that the fungal group survived more than the nonfungal group (log rank (Mantel-Cox), p < 0.001). Conclusion: Secondary fungal infections are common in COVID-19 patients admitted to the ICU. Longer treatment with corticosteroids, increased length of hospital and ICU stay, and greater length of mechanical ventilation significantly increase the risk of fungal infections. Fungal infection, however, was not associated with an increase in mortality.

2.
J Intensive Care Soc ; 24(2): 224-226, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37260426

RESUMO

Blood for coagulation analysis can be sampled from the arterial or venous system in intensive care units (ICU). The determination of clot microstructure and strength by fractal analysis (df) gives valuable information in a range of vascular haemostatic disease and sepsis. We aimed to determine if df could be measured equally and comparatively in arterial or venous blood, and 45 critically ill patients in an ICU were recruited. df was found to be readily measured in arterial blood with results comparable to those in venous blood and that add value of df as a potential marker of haemostasis in these patients.

3.
Bone Joint J ; 105-B(5): 487-495, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37121596

RESUMO

The early diagnosis of cauda equina syndrome (CES) is crucial for a favourable outcome. Several studies have reported the use of an ultrasound scan of the bladder as an adjunct to assess the minimum post-void residual volume of urine (mPVR). However, variable mPVR values have been proposed as a threshold without consensus on a value for predicting CES among patients with relevant symptoms and signs. The aim of this study was to perform a meta-analysis and systematic review of the published evidence to identify a threshold mPVR value which would provide the highest diagnostic accuracy in patients in whom the diagnosis of CES is suspected. The search strategy used electronic databases (PubMed, Medline, EMBASE, and AMED) for publications between January 1996 and November 2021. All studies that reported mPVR in patients in whom the diagnosis of CES was suspected, followed by MRI, were included. A total of 2,115 studies were retrieved from the search. Seven fulfilled the inclusion criteria. These included 1,083 patients, with data available from 734 being available for meta-analysis. In 125 patients, CES was confirmed by MRI. The threshold value of mPVR reported in each study varied and could be categorized into 100 ml, 200 ml, 300 ml, and 500 ml. From the meta-analysis, 200 ml had the highest diagnostic accuracy, with 82% sensitivity (95% confidence interval (CI) 0.72 to 0.90) and 65% specificity (95% CI 0.70 to 0.90). When compared using summative receiver operating characteristic curves, mPVR of 200 ml was superior to other values in predicting the radiological confirmation of CES. mPVR is a useful tool when assessing patients in whom the diagnosis of CES is suspected. Compared with other values a mPVR of 200 ml had superior sensitivity, specificity, and positive and negative predictive values. In a patient with a suggestive history and clinical findings, a mPVR of > 200 ml should further raise the suspicion of CES. Caution is recommended when considering the mPVR in isolation and using it as an 'exclusion tool', and it should only be used as an adjunct to a full clinical assessment.


Assuntos
Síndrome da Cauda Equina , Humanos , Volume Residual , Estudos Retrospectivos , Bexiga Urinária , Valor Preditivo dos Testes
4.
Clin Hemorheol Microcirc ; 84(3): 333-344, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36442189

RESUMO

BACKGROUND: A significant degree of mortality and morbidity in COVID-19 is through thromboembolic complications, only partially mitigated by anticoagulant therapy. Reliable markers of infection severity are not fully established. OBJECTIVES: This study investigated whether visco-elastic biomarkers predict disease severity on presentation to the Emergency Department (ED) and how they measure response to anticoagulationMETHODS:Patients testing positive for COVID-19 at a large University Teaching Hospital ED were recruited at presentation. Multiple blood samples were taken throughout hospital admission to monitor disease progression with end outcome recorded. Visco-elastic markers, fractal dimension (df) and Time to Gel Point (TGP) which measure the properties of the incipient clot were compared in patients with and without anticoagulation by Low Molecular Weight Heparin (LMWH). RESULTS: TGP and df did not predict severity of infection with COVID-19. Although LMWH prolonged TGP, there was no change in df indicating LMWH did not change clot microstructure. CONCLUSIONS: Therapeutic efficacy of LMWH appears blunted in COVID-19 infection. This may be due to the inflammatory state creating a resistance to LMWH activity, which may explain why LMWH appears less effective in COVID-19 compared to other disease states. COVID-19 was not predicted by visco-elastic testing at the time of ED presentation.


Assuntos
COVID-19 , Trombose , Humanos , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina de Baixo Peso Molecular/farmacologia , Anticoagulantes/uso terapêutico , Anticoagulantes/farmacologia , Coagulação Sanguínea , Heparina/farmacologia
5.
Respir Res ; 23(1): 303, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335329

RESUMO

Blood levels of the soluble receptor for advanced glycation end-products (sRAGE) are acutely elevated during the host inflammatory response to infection and predict mortality in COVID-19. However, the prognostic performance of this biomarker in the context of treatments to reduce inflammation is unclear. In this study we investigated the association between sRAGE and mortality in dexamethasone-treated COVID-19 patients. We studied 89 SARS-CoV-2 positive subjects and 22 controls attending the emergency department of a University Teaching Hospital during the second wave of COVID-19 and measured sRAGE at admission. In positive individuals sRAGE increased with disease severity and correlated with the National Early Warning Score 2 (Pearson's r = 0.56, p < 0.001). Fourteen out of 72 patients treated with dexamethasone died during 28 days of follow-up. Survival rates were significantly lower in patients with high sRAGE (> 3532 pg/mL) than in those with low sRAGE (p = 0.01). Higher sRAGE levels were associated with an increased risk of death after adjustment for relevant covariates. In contrast, IL-6 did not predict mortality in these patients. These results demonstrate that sRAGE remains an independent predictor of mortality among COVID-19 patients treated with dexamethasone. Determination of sRAGE could be useful for the clinical management of this patient population.


Assuntos
Tratamento Farmacológico da COVID-19 , Humanos , Receptor para Produtos Finais de Glicação Avançada , SARS-CoV-2 , Biomarcadores , Dexametasona/uso terapêutico , Produtos Finais de Glicação Avançada
6.
Clin Hemorheol Microcirc ; 82(2): 183-191, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35694917

RESUMO

BACKGROUND: A significant degree of mortality and morbidity in Covid-19 is due to thromboembolic disease. Coagulopathy has been well described in critically unwell patients on ICU. There is less clear evidence regarding these changes at the time of presentation to the Emergency Department and the progression of disease over time. OBJECTIVE: We sought to investigate whether coagulation markers can predict severity and how they change over the disease course. METHODS: Patients presenting to a single University Teaching Hospital were recruited and followed up if PCR was positive. Alongside routine blood testing, Rotational Thromboelastometry (ROTEM) was performed. Outcome data was recorded for all patients, and ROTEM values were compared across outcome groups. RESULTS: Extem and Intem Maximum Lysis were significantly reduced in those who died or required an ICU admission, indicating a reduced ability to break down clot mass in the most critically unwell patients. CONCLUSION: Comparisons between groups demonstrated that one distinguishing feature between those who require ICU admission or die of Covid-19 compared with those who survive a hospital stay to discharge was the extent to which fibrinolysis could occur. Mortality and morbidity in Covid-19 infection appears in part driven by an inability to break down clot mass.


Assuntos
Transtornos da Coagulação Sanguínea , COVID-19 , Humanos , Fibrinólise , Tromboelastografia , Testes de Coagulação Sanguínea
7.
Nitric Oxide ; 122-123: 6-18, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35202833

RESUMO

BACKGROUND: Extracellular vesicles (EVs) derived from endothelial cells are elevated in cardiovascular disease and promote inflammation and coagulation. Hypoxia is often a key feature and is itself a potent stimulator of increased EV production. Inorganic nitrite (NO2-) has beneficial and protective effects that are enhanced in hypoxia. OBJECTIVES: Investigate the impact of hypoxia on the functional capacity of EV derived from endothelial cells under hypoxia, and assess whether pre-treatment of endothelial cells with NO2- can alter EV function. METHODS: Differential ultracentrifugation was used to isolate EV from the cultured endothelial cell line HECV (CEV), and from primary human umbilical cord derived endothelial cells (PEV), with time-resolved fluorescence used to assess EV protein composition. Clot formation was induced by thrombin and calcium in two assays; using an Alexa Fluor 594 human fibrinogen conjugate assay and standard turbidometry. Platelet aggregation was determined using multiple electrode aggregometry. Scanning electron microscopy was used to visualise fibrin clots. RESULTS: Hypoxia exposure (1% O2) significantly increased CEV production in comparison to normoxia (21% O2) (1825 ± 72 EVs/cell vs 117 ± 9 EVs/cell, p < 0.001, respectively) but had no effect on CEV mean size (221 ± 6 nm vs 203 ± 4 nm, p > 0.05). Hypoxia-derived PEVs contained significantly more tissue factor than normoxia-derived EVs (Relative Fluorescence Units (RFU) = 7666 ± 1698 vs 5958 ± 1644, p < 0.001, respectively) and less tissue factor pathway inhibitor (RFU = 9799 ± 2353 vs 19723 ± 2698, p < 0.05). Hypoxia significantly increased CEV induced fibrin polymer formation compared to normoxia (% area = 46.98 ± 0.97 vs 36.36 ± 0.72, p < 0.05). Pre-treatment of endothelial cells with NO2- in hypoxia abrogated this effect (% area = 15.70 ± 1.99, p < 0.001). Hypoxia derived CEV non-significantly increased the maximum clot formed, shortened time to max clot, and increased time to clot lysis by turbidometry. ADP-mediated platelet aggregation was significantly elevated with PEV derived from hypoxia compared to normoxia (888.0 ± 32.2 AU*min vs 671.5.2 ± 28.3 AU*min, p < 0.01). This was abrogated by pre-treatment of hypoxic endothelial cells with NO2- (716.5 ± 744.3 AU*min, p < 0.001). CONCLUSIONS: Hypoxia-derived PEVs and CEVs exhibit increased procoagulant activity compared to normoxia-derived EVs, which we confirm to be mediated by an imbalance of TF/TFPI. Pre-treatment of endothelial cells with NO2- reduces the pro-coagulant activity of EVs via a mechanism that is Hypoxia-inducible factor 1 (HIF-1) dependent, but independent of TF/TFPI.


Assuntos
Vesículas Extracelulares , Trombose , Células Endoteliais/metabolismo , Vesículas Extracelulares/metabolismo , Fibrina/metabolismo , Fibrina/farmacologia , Humanos , Hipóxia/metabolismo , Nitritos/metabolismo , Dióxido de Nitrogênio , Tromboplastina/metabolismo , Tromboplastina/farmacologia , Trombose/metabolismo
8.
J Forensic Sci ; 67(1): 169-179, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34747497

RESUMO

From a forensic perspective, a presumptive test, one which indicates the presence or absence of a certain target material such as blood, is an invaluable tool. Among these tests, there are different specificities, sensitivities, and shelf lives. The accuracy of a test is an algebraic combination of the specificity and sensitivity of the test. Each test has limitations as given by its false positive and false negative rates. The aim of this study was to illustrate how the false positive and false negative rates are to be properly determined using a simulation study for the phenolphthalein test. New presumptive tests must be properly evaluated/validated through testing of commonly encountered household items and other potentially probative items usually found at crime scenes, however, the makeup of test sets must appropriately capture all error rates. In order to correctly use these results when the test is applied to an unknown sample recovered at a crime scene, the error rates cannot be applied directly to estimate whether or not the sample is actually the analyte of interest. In a validation study, the forensic scientist calculates the false positive rate as the p(Positive Reaction|Blood), whereas at the scene, the crime scene investigator wishes to determine the p(Blood|Positive Reaction). All crime scene investigators need to ensure that the conditional is not transposed when interpreting such results. Furthermore, this work provides a model for the assessment of a multiple test diagnostic system intended for investigators.


Assuntos
Medicina Legal , Fenolftaleína , Projetos de Pesquisa , Sensibilidade e Especificidade
9.
Food Nutr Bull ; 43(1): 14-24, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34872381

RESUMO

PURPOSE: This study aimed to translate and test the content validity and reliability of an English questionnaire used in the American food and health survey. METHODS: The questionnaire was developed using 6 stages, then examined for test-retest. A total of 672 participants were recruited for validation and reliability. Validity test was performed using a correlation coefficient to measure the linear correlation between 2 questions at one given time. Moreover, the Kaiser-Meyer-Olkin, Measure of Sampling Adequacy, and Bartlett's Test of Sphericity were performed to statistically determine the suitability for conducting exploratory factor analysis. Furthermore, reliability tests using Cronbach α was used to estimate the reliability coefficient properties of the translated scale. Finally, the most important correlated questions was plotted using a color-coded correlogram. RESULTS: The test-retest reliability of all tested items was significantly correlated. The reliability test for all questions was 0.9. The cross-correlation test showed that all questions of the translated questionnaire were correlated significantly (P < .05) indicating reliability of the questionnaire. CONCLUSION: The tested questionnaire is applicable and may be used in population-based studies to raise awareness regarding health, food consumption, nutrition, and food safety among people in Jordan and/or other Arab countries.


Assuntos
Alimentos , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
10.
J Forensic Sci ; 66(5): 1704-1720, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34057735

RESUMO

The forensic science pattern comparison areas, including fingerprints, footwear, and firearms, have been criticized for their subjective nature. While much research has attempted to move these disciplines to more objective methods, examiners are still coming to conclusions based on their own training and experience. To complement this subjectivity, black box studies are necessary to establish the accuracy of these feature-comparison methods. However, when cartridges are fired by a firearm to create cartridge case test sets there may be significant variability within the resulting impressions. This can result in different participants receiving test sets with varying levels of difficulty based on differences in impression quality. Therefore, comparison of accuracy between examiners is not straightforward. To compare accuracy between examiners, a method called double-casting was used to create plastic cartridge case reproductions. Double-casts of twenty-one test sets of master cartridge cases were created and mailed to firearm examiners. The double-casts ensured that all participants were comparing exhibits with the same level of detail. The examiners were tasked with determining if the unknown cartridge case in each set was fired by the same firearm as the three knowns. Automated comparisons were also used to compare the cartridge cases within each set. The results from this study showed that there are differences in examiner conclusions when examining the same evidence. Furthermore, it was shown that automated comparison metrics would benefit examiners as a quality control measure to correct any potential errors and strengthen conclusions.

11.
Bone Jt Open ; 2(5): 293-300, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33940937

RESUMO

AIMS: "Get It Right First Time" (GIRFT) and NHS England's Best Practice Tariff (BPT) have published directives advising that patients over the ages of 65 (GIRFT) and 69 years (BPT) receiving total hip arthroplasty (THA) should receive cemented implants and have brought in financial penalties if this policy is not observed. Despite this, worldwide, uncemented component use has increased, a situation described as a 'paradox'. GIRFT and BPT do, however, acknowledge more data are required to support this edict with current policies based on the National Joint Registry survivorship and implant costs. METHODS: This study compares THA outcomes for over 1,000 uncemented Corail/Pinnacle constructs used in all age groups/patient frailty, under one surgeon, with identical pre- and postoperative pathways over a nine-year period with mean follow-up of five years and two months (range: nine months to nine years and nine months). Implant information, survivorship, and regular postoperative Oxford Hip Scores (OHS) were collected and two comparisons undertaken: a comparison of those aged over 65 years with those 65 and under and a second comparison of those aged 70 years and over with those aged under 70. RESULTS: Overall revision rate was 1.3% (13/1,004). A greater number of revisions were undertaken in those aged over 65 years, but numbers were small and did not reach significance. The majority of revisions were implant-independent. Single component analysis revealed a 99.9% and 99.6% survival for the uncemented cup and femoral component, respectively. Mean patient-reported outcome measures (PROMs) improvement for all ages outperformed the national PROMs and a significantly greater proportion of those aged over 65/69 years reached and maintained a meaningful improvement in their OHS earlier than their younger counterparts (p < 0.05/0.01 respectively). CONCLUSION: This study confirms that this uncemented THA system can be used safely and effectively in patient groups aged over 65 years and those over 69 years, with low complication and revision rates. Cite this article: Bone Jt Open 2021;2(5):293-300.

12.
Clin Hemorheol Microcirc ; 77(2): 183-194, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32925001

RESUMO

BACKGROUND: Diabetic ketoacidosis (DKA) is a medical emergency with a high mortality rate and is associated with severe metabolic acidosis and dehydration. DKA patients have an increased risk of arterial and venous thromboembolism, however little is known about this metabolic derangement in the first 24 hours of admission and to assess its effect on coagulation. We therefore utilised a novel functional marker of clot microstructure (fractal dimension - df) to assess these changes within the first 24 hours. METHODS: Prospective single centre observational study to demonstrate whether the tendency of blood clot formation differs in DKA patients. RESULTS: 15 DKA patients and 15 healthy matched controls were recruited. Mean df in the healthy control group was 1.74±0.03. An elevated df of 1.78±0.07 was observed in patients with DKA on admission. The mean pH on admission was 7.14±0.13 and the lactate was 3.6±2.0. df changed significantly in response to standard treatment and was significantly reduced to 1.68±0.09 (2-6& h) and to 1.66±0.08 at 24& h (p < 0.01 One-way ANOVA). df also correlated significantly with lactate and pH (Pearson correlation coefficient 0.479 and -0.675 respectively, p < 0.05). CONCLUSIONS: DKA patients at presentation have a densely organising less permeable thrombogenic clot microstructure as evidenced by high df. These structural changes are due to a combination of dehydration and a profound metabolic acidosis, which was reversed with treatment. These changes were not mirrored in standard clinical markers of thromboge-nicity.


Assuntos
Biomarcadores/sangue , Cetoacidose Diabética/tratamento farmacológico , Hemorreologia/fisiologia , Trombose/tratamento farmacológico , Estudos de Casos e Controles , Cetoacidose Diabética/sangue , Feminino , Fractais , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
13.
J Forensic Sci ; 65(6): 1945-1953, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32898293

RESUMO

Due to the shot-to-shot variability in tool mark reproduction on fired cartridge cases, a method of replication is needed for the creation of training and testing sets. Double-casting is one method that has been used for this application, but the accuracy and variability of this method needs to be characterized. Three firearms were used to fire 25 cartridges each to create the master cartridge cases. The double-casting method consists of creating a silicone mold of the master cartridge case. A plastic resin mix is then poured into the mold to create the double-cast reproduction. Fifteen double-casts of each of the 75 fired cartridge cases were created across different silicone molds to analyze within- and between-mold variability. The master cartridge cases and double-casts were scanned with a confocal microscope (Sensofar® S neox) to create three-dimensional representations of the surfaces. Two similarity metrics were used for the objective comparison of the double-casts to their master cartridge cases: the areal correlation coefficient (ACCFMAX ) and the number of congruent matching cells (CMC). The ACCFMAX and CMC data, along with visual examinations, showed that the double-casting method produces accurate reproductions. Within-mold variability was found to be minimal, and between-mold variability was low. These results illustrate that double-casting can be applied for training and testing purposes.

14.
SAGE Open Med ; 8: 2050312120946244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32782799

RESUMO

OBJECTIVES: Peripheral artery disease is a major cardiovascular disease affecting more than 200 million people globally and up to 4 times more frequent in the diabetic population. It can lead to lower extremity amputations or revascularisation and is associated with an increased risk of myocardial infarction, stroke and early mortality. This novel cross-sectional study aimed to explore the feasibility and acceptability of incorporating diabetic foot screening at routine diabetic retinopathy screening appointments. METHODS: Participants underwent foot screening during the interval between pupil dilatation and retinal photography as part of the eye screening procedure. Lower limb arterial assessment included ankle brachial index, pulse volume waveform and protective light touch sensation. RESULTS: Of 364 participants invited, 88% (n = 321) met the inclusion criteria. About 26.4% (n = 86) had asymptomatic peripheral artery disease and 3% (n = 10) had peripheral sensory neuropathy. Binary logistical regression analysis identified age (p < 0.005), existing coronary heart disease (p < 0.005) and gender (p = 0.03) as predictors of peripheral artery disease. CONCLUSION: Incorporating foot examination during eye screening appointments is feasible and was well received by participants and staff alike. Undiagnosed early peripheral artery disease was evident in a third of the study population emphasising the benefit of introducing foot surveillance into eye screening appointments for the early identification of lower limb arterial disease and peripheral sensory neuropathy.

15.
Mov Ecol ; 8: 18, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32391154

RESUMO

BACKGROUND: Where mesopredators co-exist with dominant apex predators, an understanding of the factors that influence their habitat and space use can provide insights that help guide wildlife conservation and pest management actions. A predator's habitat use is defined by its home range, which is influenced by its selection or avoidance of habitat features and intra- and inter-specific interactions within the landscape. These are driven by both innate and learned behaviour, operating at different spatial scales. We examined the seasonal home ranges and habitat selection of actively-managed populations of a native apex predator (dingo Canis dingo) and invasive mesopredator (feral cat Felis catus) in semi-arid Western Australia to better understanding their sympatric landscape use, potential interactions, and to help guide their management. METHODS: We used kernel density estimates to characterise the seasonal space use of dingoes and feral cats, investigate inter- and intra-species variation in their home range extent and composition, and examine second-order habitat selection for each predator. Further, we used discrete choice modelling and step selection functions to examine the difference in third-order habitat selection across several habitat features. RESULTS: The seasonal home ranges of dingoes were on average 19.5 times larger than feral cats. Feral cat seasonal home ranges typically included a larger proportion of grasslands than expected relative to availability in the study site, indicating second-order habitat selection for grasslands. In their fine-scale movements (third-order habitat selection), both predators selected for roads, hydrological features (seasonal intermittent streams, seasonal lakes and wetlands), and high vegetation cover. Dingoes also selected strongly for open woodlands, whereas feral cats used open woodlands and grasslands in proportion to availability. MANAGEMENT RECOMMENDATIONS: Based on these results, and in order to avoid unintended negative ecological consequences (e.g. mesopredator release) that may stem from non-selective predator management, we recommend that feral cat control focuses on techniques such as trapping and shooting that are specific to feral cats in areas where they overlap with apex predators (dingoes), and more general techniques such as poison baiting where they are segregated.

16.
Adv Protein Chem Struct Biol ; 119: 157-198, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31997768

RESUMO

Antibodies have provided invaluable treatment options for many diseases, with immunotherapy revolutionising the treatment of several inflammatory disorders including inflammatory bowel disease (IBD). Accumulating evidence suggests that IBD results from an inappropriate response to intestinal microbes and environmental factors in genetically susceptible individuals, with overactivity of the pro-inflammatory pathways. On a pathophysiological level, IBD is a complex disease with intestinal fibrosis, stenosis and an increased incidence of cancer observed in those whose disease is inadequately controlled over time. Regulating the actions of the pro-inflammatory cytokine human tumor necrosis factor-alpha (hTNFα) through the use of anti-TNFα monoclonal antibodies (e.g. infliximab, certolizumab, adalimumab and golimumab) has proven an effective intervention for IBD with their increased use a testament of their effectiveness. These agents are administered systemically thereby causing their distribution throughout the body in a condition that is localised to the gastrointestinal (GI) tract. Immunogenicity, the induction of anti-drug antibodies (ADAs), serum sickness and other undesirable side effects limit their use, whilst up to 50% of patients do not respond to initial therapy. Diseases confined to the GI tract are ideal for targeting by oral therapy which mitigates side effects and allows for lower doses to be administered. Several oral anti-TNFα agents have been investigated with success but are not yet in general clinical use. This partially reflects the fact that the oral administration of antibodies has many barriers including the harsh environment of the GI tract and the presence of enzymes including pepsin, trypsin and chymotrypsin in the intestine which provide significant challenges to targeted oral therapy.


Assuntos
Anticorpos Monoclonais/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Administração Oral , Animais , Anticorpos Monoclonais/administração & dosagem , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
BMJ Open Sport Exerc Med ; 5(1): e000622, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749983

RESUMO

OBJECTIVES: To establish quantitative values of stiffness for the gastrocnemius muscle in patients diagnosed with Achilles tendinopathy. DESIGN: Case-control study with a single (cross sectional) time point of patients diagnosed with unilateral Achilles tendinopathy and an asymptomatic group. METHODS: Sample of 50 participants: 25 participants with symptomatic unilateral Achilles tendinopathy (symptomatic group) with the asymptomatic side of this group used as a control (control group 1). A third group of 25 participants with asymptomatic Achilles tendons (control group 2). Mechanical stiffness parameters, including natural oscillation frequency (F), dynamic stiffness (S), mechanical stress relaxation time (R), logarithmic decrement (D) and creep (C), were assessed using the MyotonPRO. Measurements at the medial and lateral gastrocnemii were taken as non-weight bearing (NWB) and weight bearing (WB). RESULTS: Significant (p<0.05) differences were observed between the mean symptomatic group and control groups 1 and 2 in the WB and NWB conditions for natural oscillation frequency (F), dynamic stiffness (S), and creep (C). There was a significant reduction in S WB and conversely a significant increase in S of the symptomatic group NWB. Creep (C) and mechanical stress relaxation time (R) were significantly (p<0.05) less in the symptomatic group NWB. Significant differences were observed between the NWB and WB data sets for logarithmic decrement (D). NWB D demonstrated significantly (p<0.05) higher scores than the WB condition. CONCLUSION: This study demonstrated that there was a significant reduction in stiffness of the gastrocnemius muscle in participants with Achilles tendinopathy compared with the two control groups. The WB MyotonPRO measures for the symptomatic groups of F and S were significantly lower, indicating a decrease in the tonal properties (F) and dynamic stiffness (S) of the muscle. The application of MyotonPRO technology to measure changes in stiffness in the gastrocnemius muscle may be useful to measure as part of a rehabilitation programme where specific attention could be placed to increase the tonal properties of the muscle. Further studies are required to develop a robust clinical application of this technology, particularly with regard to Achilles tendinopathy.

18.
Genes (Basel) ; 10(9)2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31546973

RESUMO

The use of multiple source populations provides a way to maximise genetic variation and reduce the impacts of inbreeding depression in newly established translocated populations. However, there is a risk that individuals from different source populations will not interbreed, leading to population structure and smaller effective population sizes than expected. Here, we investigate the genetic consequences of mixing two isolated, morphologically distinct island populations of boodies (Bettongia lesueur) in a translocation to mainland Australia over three generations. Using 18 microsatellite loci and the mitochondrial D-loop region, we monitored the released animals and their offspring between 2010 and 2013. Despite high levels of divergence between the two source populations (FST = 0.42 and ϕST = 0.72), there was clear evidence of interbreeding between animals from different populations. However, interbreeding was non-random, with a significant bias towards crosses between the genetically smaller-sized Barrow Island males and the larger-sized Dorre Island females. This pattern of introgression was opposite to the expectation that male-male competition or female mate choice would favour larger males. This study shows how mixing diverged populations can bolster genetic variation in newly established mammal populations, but the ultimate outcome can be difficult to predict, highlighting the need for continued genetic monitoring to assess the long-term impacts of admixture.


Assuntos
Introgressão Genética , Potoroidae/genética , Translocação Genética , Animais , Ecossistema , Feminino , Genótipo , Masculino
19.
Int J Parasitol Parasites Wildl ; 10: 13-22, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31334028

RESUMO

Fauna translocations play an integral role in the management of threatened wildlife, though we are limited by our understanding of how the host-parasite community changes during translocation. During this longitudinal field-based study, we monitored gastrointestinal, blood-borne and ectoparasite taxa infecting woylies (Bettongia penicillata) for up to 12 months following two fauna translocations to supplement existing wild woylie populations in three different sites (Dryandra, Walcott and Warrup East) within the south-west of Western Australia. We aimed to (a) identify changes in parasite community structure of both translocated and resident woylies following translocation; and (b) evaluate the efficacy of ivermectin treatment in translocated hosts. Destination site and time since translocation had the strongest effects on parasite prevalence and mean faecal egg counts following translocation. Ivermectin treatment did not significantly reduce parasite prevalence or mean faecal egg counts in treated hosts. Prior to translocation, parasite community composition differed significantly between woylies selected for translocation and resident woylies within each release site. Following translocation, the parasite communities of translocated and resident hosts converged to become more similar over time, with loss of parasite taxa and novel host-parasite associations emerging. This is the first study to examine changes to the broader parasite community in translocated and resident animals following translocation. The dominant site-specific response of parasites following translocation reinforces the importance of incorporating parasite studies to enhance our fundamental understanding of perturbations in host-parasite systems during translocation, in particular the site-level drivers of parasite dynamics.

20.
Parasit Vectors ; 12(1): 126, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30898141

RESUMO

BACKGROUND: Understanding how fauna translocation and antiparasitic drug treatment impact parasite community structure within a host is vital for optimising translocation outcomes. Trypanosoma spp. and piroplasms (Babesia and Theileria spp.) are known to infect Australian marsupials, including the woylie (Bettongia penicillata). However relatively little is known about these haemoparasites, or how they respond to management practices such as translocation. We monitored haemoparasites infecting woylies for up to 12 months during two fauna translocations to supplement existing woylie populations in three different sites (Dryandra, Walcott and Warrup East) within south-western Australia between 2014 and 2016, with the aim of investigating (i) how haemoparasite prevalence, Trypanosoma spp. richness and Trypanosoma spp. community composition varied over time and between different sites following translocation; and (ii) whether ivermectin treatment indirectly impacts haemoparasite prevalence. Using molecular methods, 1211 blood samples were screened for the presence of trypanosomes, and a subset of these samples (n = 264) were also tested for piroplasms. RESULTS: Trypanosomes and piroplasms were identified in 55% and 94% of blood samples, respectively. We identified five Trypanosoma species, two Theileria species, a single species of Babesia and a novel Bodo species. Trypanosoma spp. richness and the prevalence of haemoparasite co-infection increased after translocation. Prior to translocation, Trypanosoma spp. community composition differed significantly between translocated and resident woylies within Walcott and Warrup East, but not Dryandra. Six months later, there was a significant difference between translocated and resident woylies within Dryandra, but not Walcott or Warrup East. The response of haemoparasites to translocation was highly site-specific, with predominant changes to the haemoparasite community in translocated woylies occurring within the first few months following translocation. Ivermectin treatment had no significant effect on haemoparasite prevalence. CONCLUSIONS: This study contributes to our understanding of haemoparasite dynamics in woylies following translocation. The highly site-specific and rapid response of haemoparasites to translocation highlights the need to better understand what drives these effects. Given that haemoparasite prevalence and composition of translocated and resident animals changed significantly following translocation, we propose that parasite monitoring should form an essential component of translocation protocols, and such protocols should endeavour to monitor translocated hosts and cohabiting species.


Assuntos
Potoroidae/parasitologia , Tripanossomíase/veterinária , Animais , Antiprotozoários/administração & dosagem , Austrália/epidemiologia , Babesia , Babesiose/sangue , Babesiose/complicações , Babesiose/epidemiologia , Coinfecção/veterinária , Feminino , Ivermectina/administração & dosagem , Masculino , Filogeografia , Prevalência , Theileria , Theileriose/sangue , Theileriose/complicações , Theileriose/epidemiologia , Trypanosoma , Tripanossomíase/complicações , Tripanossomíase/epidemiologia , Tripanossomíase/parasitologia
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