Medicine, Dentistry & Health Sciences Collected Works - Research Publications
Now showing items 1-48 of 928
Artificial Intelligence and Telehealth may Provide Early Warning of Epidemics.
(Frontiers Media SA, 2021)
The COVID-19 pandemic produced a very sudden and serious impact on public health around the world, greatly adding to the burden of overloaded professionals and national medical systems. Recent medical research has demonstrated the value of using online systems to predict emerging spatial distributions of transmittable diseases. Concerned internet users often resort to online sources in an effort to explain their medical symptoms. This raises the prospect that incidence of COVID-19 may be tracked online by search queries and social media posts analyzed by advanced methods in data science, such as Artificial Intelligence. Online queries can provide early warning of an impending epidemic, which is valuable information needed to support planning timely interventions. Identification of the location of clusters geographically helps to support containment measures by providing information for decision-making and modeling.
Microsphere integrated microfluidic disk: synergy of two techniques for rapid and ultrasensitive dengue detection
(NATURE PUBLISHING GROUP, 2015-11-09)
The application of microfluidic devices in diagnostic systems is well-established in contemporary research. Large specific surface area of microspheres, on the other hand, has secured an important position for their use in bioanalytical assays. Herein, we report a combination of microspheres and microfluidic disk in a unique hybrid platform for highly sensitive and selective detection of dengue virus. Surface engineered polymethacrylate microspheres with carefully designed functional groups facilitate biorecognition in a multitude manner. In order to maximize the utility of the microspheres' specific surface area in biomolecular interaction, the microfluidic disk was equipped with a micromixing system. The mixing mechanism (microballoon mixing) enhances the number of molecular encounters between spheres and target analyte by accessing the entire sample volume more effectively, which subsequently results in signal amplification. Significant reduction of incubation time along with considerable lower detection limits were the prime motivations for the integration of microspheres inside the microfluidic disk. Lengthy incubations of routine analytical assays were reduced from 2 hours to 5 minutes while developed system successfully detected a few units of dengue virus. Obtained results make this hybrid microsphere-microfluidic approach to dengue detection a promising avenue for early detection of this fatal illness.
A Portable Automatic Endpoint Detection System for Amplicons of Loop Mediated Isothermal Amplification on Microfluidic Compact Disk Platform
(MDPI AG, 2015-03-01)
In recent years, many improvements have been made in foodborne pathogen detection methods to reduce the impact of food contamination. Several rapid methods have been developed with biosensor devices to improve the way of performing pathogen detection. This paper presents an automated endpoint detection system for amplicons generated by loop mediated isothermal amplification (LAMP) on a microfluidic compact disk platform. The developed detection system utilizes a monochromatic ultraviolet (UV) emitter for excitation of fluorescent labeled LAMP amplicons and a color sensor to detect the emitted florescence from target. Then it processes the sensor output and displays the detection results on liquid crystal display (LCD). The sensitivity test has been performed with detection limit up to 2.5 × 10(-3) ng/µL with different DNA concentrations of Salmonella bacteria. This system allows a rapid and automatic endpoint detection which could lead to the development of a point-of-care diagnosis device for foodborne pathogens detection in a resource-limited environment.
Prognostic significance of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in patients with oropharyngeal cancer treated with radiotherapy
BACKGROUND: This study aimed to evaluate the prognostic value of pre-treatment NLR in patients with oropharyngeal cancer. METHODS: Patients who completed definitive radiotherapy (RT) for oropharyngeal cancer and had blood counts taken pre-RT from 2002 to 2013 were included. NLR was calculated as total neutrophil/lymphocytes. Survival rates were estimated using the Kaplan-Meier method. Univariable and multivariable analyses were conducted with linear and Cox regression methods. NLR was analysed posteriori and dichotomised on the discovered median. RESULTS: Eight hundred and forty-eight patients were analysed. The median pre-RT NLR was 3. Patients with NLR of <3 had improved overall survival (OS) than those with NLR ≥ 3 (5-year OS 85 vs 74%, p < 0.0001). OS differences remained significant when stratified according to HPV status (HPV-positive p = 0.011; HPV-negative p = 0.003). Freedom from any recurrence (FFR), locoregional control (LRC) and freedom of distant recurrence (FDR) were better in those with NLR < 3. The negative impact of elevated pre-RT NLR on OS (HR = 1.64, p = 0.001), FFR (HR = 1.6, p = 0.006) and LRC (HR = 1.8, p = 0.005) remained significant on multivariable analysis. CONCLUSIONS: Pre-RT NLR is an independent prognostic factor in patients with oropharyngeal cancer regardless of HPV status. Patients with lower NLR had more favourable OS and disease control.
Characterisation of complexes formed by parasite proteins exported into the host cell compartment of Plasmodium falciparum infected red blood cells
During its intraerythrocytic life cycle, the human malaria parasite Plasmodium falciparum supplements its nutritional requirements by scavenging substrates from the plasma through the new permeability pathways (NPPs) installed in the red blood cell (RBC) membrane. Parasite proteins of the RhopH complex: CLAG3, RhopH2, RhopH3, have been implicated in NPP activity. Here, we studied 13 exported proteins previously hypothesised to interact with RhopH2, to study their potential contribution to the function of NPPs. NPP activity assays revealed that the 13 proteins do not appear to be individually important for NPP function, as conditional knockdown of these proteins had no effect on sorbitol uptake. Intriguingly, reciprocal immunoprecipitation assays showed that five of the 13 proteins interact with all members of the RhopH complex, with PF3D7_1401200 showing the strongest association. Mass spectrometry-based proteomics further identified new protein complexes; a cytoskeletal complex and a Maurer's clefts/J-dot complex, which overall helps clarify protein-protein interactions within the infected RBC (iRBC) and is suggestive of the potential trafficking route of the RhopH complex itself to the RBC membrane.
The Ethics of Motivational Neuro-Doping in Sport: Praiseworthiness and Prizeworthiness
Motivational enhancement in sport - a form of 'neuro-doping' - can help athletes attain greater achievements in sport. A key question is whether or not that athlete deserves that achievement. We distinguish three concepts - praiseworthiness (whether the athlete deserves praise), prizeworthiness (whether the athlete deserves the prize), and admiration (pure admiration at the performance) - which are closely related. However, in sport, they can come apart. The most praiseworthy athlete may not be the most prizeworthy, and so on. Using a model of praiseworthiness as costly commitment to a valuable end, and situating prizeworthiness within the boundaries of the sport, we argue that motivational enhancement in some cases can be compatible with desert.
Progression of Geographic Atrophy: Epistemic Uncertainties Affecting Mathematical Models and Machine Learning
(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2021-11-01)
Purpose: The purpose of this study was to identify a taxonomy of epistemic uncertainties that affect results for geographic atrophy (GA) assessment and progression. Methods: An important source of variability is called "epistemic uncertainty," which is due to incomplete system knowledge (i.e. limitations in measurement devices, artifacts, and human subjective evaluation, including annotation errors). In this study, different epistemic uncertainties affecting the analysis of GA were identified and organized into a taxonomy. The uncertainties were discussed and analyzed, and an example was provided in the case of model structure uncertainty by characterizing progression of GA by mathematical modelling and machine learning. It was hypothesized that GA growth follows a logistic (sigmoidal) function. Using case studies, the GA growth data were used to test the sigmoidal hypothesis. Results: Epistemic uncertainties were identified, including measurement error (imperfect outcomes from measuring tools), subjective judgment (grading affected by grader's vision and experience), model input uncertainties (data corruption or entry errors), and model structure uncertainties (elucidating the right progression pattern). Using GA growth data from case studies, it was demonstrated that GA growth can be represented by a sigmoidal function, where growth eventually approaches an upper limit. Conclusion: Epistemic uncertainties contribute to errors in study results and are reducible if identified and addressed. By prior identification of epistemic uncertainties, it is possible to (a) quantify uncertainty not accounted for by natural statistical variability, and (b) reduce the presence of these uncertainties in future studies. Translational Relevance: Lowering epistemic uncertainty will reduce experimental error, improve consistency and reproducibility, and increase confidence in diagnostics.
Divergent roles of HDAC1 and HDAC2 in the regulation of epidermal development and tumorigenesis
The histone deacetylases HDAC1 and HDAC2 remove acetyl moieties from lysine residues of histones and other proteins and are important regulators of gene expression. By deleting different combinations of Hdac1 and Hdac2 alleles in the epidermis, we reveal a dosage-dependent effect of HDAC1/HDAC2 activity on epidermal proliferation and differentiation. Conditional ablation of either HDAC1 or HDAC2 in the epidermis leads to no obvious phenotype due to compensation by the upregulated paralogue. Strikingly, deletion of a single Hdac2 allele in HDAC1 knockout mice results in severe epidermal defects, including alopecia, hyperkeratosis, hyperproliferation and spontaneous tumour formation. These mice display impaired Sin3A co-repressor complex function, increased levels of c-Myc protein, p53 expression and apoptosis in hair follicles (HFs) and misregulation of HF bulge stem cells. Surprisingly, ablation of HDAC1 but not HDAC2 in a skin tumour model leads to accelerated tumour development. Our data reveal a crucial function of HDAC1/HDAC2 in the control of lineage specificity and a novel role of HDAC1 as a tumour suppressor in the epidermis.
DNA hypomethylation leads to cGAS-induced autoinflammation in the epidermis
DNA methylation is a fundamental epigenetic modification, important across biological processes. The maintenance methyltransferase DNMT1 is essential for lineage differentiation during development, but its functions in tissue homeostasis are incompletely understood. We show that epidermis-specific DNMT1 deletion severely disrupts epidermal structure and homeostasis, initiating a massive innate immune response and infiltration of immune cells. Mechanistically, DNA hypomethylation in keratinocytes triggered transposon derepression, mitotic defects, and formation of micronuclei. DNA release into the cytosol of DNMT1-deficient keratinocytes activated signaling through cGAS and STING, thus triggering inflammation. Our findings show that disruption of a key epigenetic mark directly impacts immune and tissue homeostasis, and potentially impacts our understanding of autoinflammatory diseases and cancer immunotherapy.
Development of a Machine-Learning-Based Classifier for the Identification of Head and Body Impacts in Elite Level Australian Rules Football Players.
(Frontiers Media SA, 2021)
Background: Exposure to thousands of head and body impacts during a career in contact and collision sports may contribute to current or later life issues related to brain health. Wearable technology enables the measurement of impact exposure. The validation of impact detection is required for accurate exposure monitoring. In this study, we present a method of automatic identification (classification) of head and body impacts using an instrumented mouthguard, video-verified impacts, and machine-learning algorithms. Methods: Time series data were collected via the Nexus A9 mouthguard from 60 elite level men (mean age = 26.33; SD = 3.79) and four women (mean age = 25.50; SD = 5.91) from the Australian Rules Football players from eight clubs, participating in 119 games during the 2020 season. Ground truth data labeling on the captures used in this machine learning study was performed through the analysis of game footage by two expert video reviewers using SportCode and Catapult Vision. The visual labeling process occurred independently of the mouthguard time series data. True positive captures (captures where the reviewer directly observed contact between the mouthguard wearer and another player, the ball, or the ground) were defined as hits. Spectral and convolutional kernel based features were extracted from time series data. Performances of untuned classification algorithms from scikit-learn in addition to XGBoost were assessed to select the best performing baseline method for tuning. Results: Based on performance, XGBoost was selected as the classifier algorithm for tuning. A total of 13,712 video verified captures were collected and used to train and validate the classifier. True positive detection ranged from 94.67% in the Test set to 100% in the hold out set. True negatives ranged from 95.65 to 96.83% in the test and rest sets, respectively. Discussion and conclusion: This study suggests the potential for high performing impact classification models to be used for Australian Rules Football and highlights the importance of frequencies <150 Hz for the identification of these impacts.
Microcytosis and possible early iron deficiency in paediatric inpatients: a retrospective audit.
(Springer Science and Business Media LLC, 2009-05-29)
BACKGROUND: Iron deficiency anaemia is a common paediatric problem worldwide, with significant neurodevelopmental morbidity if left untreated. A decrease in the mean corpuscular volume (MCV) can be used as a surrogate marker for detecting early iron deficiency prior to definitive investigation and treatment. An audit cycle was therefore undertaken to evaluate and improve the identification, follow-up and treatment of abnormally low MCV results amongst the paediatric inpatients in an English district general hospital. METHODS: The audit cycle was performed retrospectively over two three-month periods (February to April 2006; September to November 2006), amongst patients aged between one month and 16 years that had full blood counts performed whilst admitted on the paediatric ward. Patients with at least one abnormally low MCV result were identified, and their notes reviewed. We looked for any underlying explanation for the result, adequate documentation of the result as abnormal, and instigation of follow-up or treatment. In-between the two audit periods, the results of the first audit period were presented to the medical staff and suggestions were made for improvements in documentation and follow-up of abnormal results. The z-test was used to test for equality of proportions between the two audit samples. RESULTS: Out of 701 inpatients across both audit periods that had full blood counts, 61 (8.7%) had a low MCV result. Only 15% of patients in each audit period had an identifiable explanation for their low MCV values. Amongst the remaining 85% with either potentially explicable or inexplicable results, there was a significant increase in documentation of results as abnormal from 25% to 91% of cases between the first and second audit periods (p = 0.00 using z-test). However, there was no accompanying increase in the proportion of patients who received follow-up or treatment for their abnormal results. CONCLUSION: Abnormal red cell indices that may indicate iron deficiency are frequently missed amongst paediatric inpatients. Medical staff education and the use of appropriate protocols or pathways could further improve detection and treatment rates in this setting.
Plant Growth Promotion Diversity in Switchgrass-Colonizing, Diazotrophic Endophytes.
(Frontiers Media SA, 2021)
Endophytic nitrogen-fixing (diazotrophic) bacteria are essential members of the microbiome of switchgrass (Panicum virgatum), considered to be an important commodity crop in bioenergy production. While endophytic diazotrophs are known to provide fixed atmospheric nitrogen to their host plant, there are many other plant growth-promoting (PGP) capabilities of these organisms to be demonstrated. The diversity of PGP traits across different taxa of switchgrass-colonizing endophytes is understudied, yet critical for understanding endophytic function and improving cultivation methods of important commodity crops. Here, we present the isolation and characterization of three diazotrophic endophytes: Azospirillum agricola R1C, Klebsiella variicola F10Cl, and Raoultella terrigena R1Gly. Strains R1C and F10Cl were isolated from switchgrass and strain R1Gly, while isolated from tobacco, is demonstrated herein to colonize switchgrass. Each strain exhibited highly diverse genomic and phenotypic PGP capabilities. Strain F10Cl and R1Gly demonstrated the highest functional similarity, suggesting that, while endophyte community structure may vary widely based on host species, differences in functional diversity are not a clearly delineated. The results of this study advance our understanding of diazotrophic endophyte diversity, which will allow us to design robust strategies to improve cultivation methods of many economically important commodity crops.
Beyond victimhood, towards citizenship: (Re)conceptualising campus climate for LGBTQ plus university students in the Australian context
Research which attends to LGBTQ+ students’ experiences in Higher Education (HE) asserts that they are more likely to be targets of physical, verbal and symbolic violence than non-LGBTQ+ students, have poorer mental health and wellbeing, and report university settings and systems as generally exclusionary and unsafe. The Australian body of research concerning LGBTQ+ people in HE is developing but remains sparse, relying largely on concepts and empirical evidence from the United States and United Kingdom. While important to understanding LGBTQ+ exclusion in HE as a global phenomenon, we argue that concepts of ‘campus climate’ and ‘harm’ are under-theorised in Australian literature. This obscures a consistent and meaningful analysis of LGBTQ+ student lived experience. As an extension, a focus on LGBTQ+ students as ‘at-risk' means understandings of the everydayness of student life and education remain limited. We suggest that by attending to the particularity of Australian HE settings, we might open our thinking to the possibilities of a global research agenda which sets out to account for similarities and differences among diverse populations while attending to LGBTQ+ students as social citizens. Ultimately, institutional frameworks that deny LGBTQ+ people full participation in university life can be critiqued meaningfully, leading to an evidence-base of equity principles, which can be implemented for LGBTQa+ students in Australia and abroad.
Spatial patterns of genetic diversity among Australian alpine flora communities revealed by comparative phylogenomics
AIM: The alpine region of mainland Australia is one of the world's 187 biodiversity hotspots. Genetic analyses of Australian alpine fauna indicate high levels of endemism on fine spatial scales, unlike Northern Hemisphere alpine systems where shallow genetic differentiation is typically observed among populations. These discrepancies have been attributed to differences in elevation and influence from glacial activity, and point to a unique phylogeographic history affecting Australian alpine biodiversity. To test generality of these findings across Australian alpine biota, we assessed patterns of genetic structure across plant species. LOCATION: The Australian Alps, Victoria, eastern Australia. METHODS: We used an economical pooled genotypingâ byâ sequencing (GBS) approach to examine patterns of genetic diversity among seven widespread species including shrubs and forbs from 16 mountain summits in the Australian Alpine National Park. Patterns of genetic structure among summit populations for each species were inferred from an average of 2,778 independent SNP loci using Bayesian phylogenomic inference and clustering approaches. RESULTS: SNP results were consistent across species in identifying deep evolutionary splits among summit communities from the Northern and Central Victorian Alpine regions. These patterns of genetic structure are also consistent with those previously reported for invertebrate and mammal taxa. However, local genetic structure was less pronounced in the plants, supporting the notion that population connectivity tends to be higher in plant species. MAIN CONCLUSION: There is deep lineage diversification between the North and Central Victorian Alpine regions, reflecting a high level of endemism. These findings differ from those reported for alpine biodiversity from New South Wales and much of the Northern Hemisphere, and support the notion that genetic diversity is typically greatest in areas least affected by historical ice sheet formation. We discuss the implications of our findings in the context of conservation planning, and highlight the benefits of this rapid and costâ effective genome scan approach for characterizing evolutionary processes at multispecies and landscape scales.
Direct access colonoscopy: impact of intervention on time to colorectal cancer diagnosis and treatment in North West Tasmania
BACKGROUND: Direct access colonoscopy (DAC) allows general practitioners to refer directly for colonoscopy, without specialist review. Research suggests DAC reduces times to diagnosis and treatment of colorectal cancer. However, there is no information about outcomes of DAC in Australia. AIM: To determine if DAC in North West Tasmania expedited colorectal diagnosis and treatment. METHODS: Pre-post intervention study evaluating time from referral to diagnosis and definitive treatment. Patient demographic characteristics, referral, colonoscopy and treatment information was retrieved from hospital records. Timelines were investigated in standard referrals (SR), emergency department/inpatient referrals and DAC using survival analysis. RESULTS: Two hundred and six colorectal cancer cases were identified (117 SR, 26 DAC, 48 emergency department/inpatient and 15 unknown pathways). Median time to colonoscopy/diagnosis (DAC 6 weeks vs SR 7 weeks, P = 0.55) or definitive treatment (surgery/chemoradiation) (DAC 8 weeks vs SR 9 weeks, P = 0.81) was not significantly improved with DAC. Among SR only, time to diagnosis was 9 weeks pre-intervention versus 5 weeks post-intervention (P = 0.13), and time to treatment was 11 weeks pre-intervention versus 6 weeks post-intervention (P = 0.07). CONCLUSION: There was no statistically significant improvement in time to colorectal cancer diagnosis or treatment among patients referred through DAC compared to SR. There was a trend towards improved waiting times for SR concurrent with the introduction of the DAC pathway, indicating improvement of all referral processes. DAC may not be effective at expediting colorectal cancer diagnosis if it is not accompanied by strict referral guidelines. Larger evaluations of DAC are required in the Australian context.
Hearing and neurodevelopmental outcomes for children with asymptomatic congenital cytomegalovirus infection: A systematic review
INTRODUCTION: Congenital CMV is one of the commonest congenital infections and a recognised cause of sensorineural hearing loss and neurodevelopmental impairment. Ninety percent are clinically inapparent at birth but are reported to be at risk of developing such abnormalities throughout childhood, the extent of which requires further elucidation. METHODS: A systematic literature review was conducted using Medline and Embase databases, manual citation review, and personal libraries for articles reporting primary data on hearing and neurodevelopmental outcomes for children with asymptomatic congenital CMV. PROSPERO registration number CRD42015025407. RESULTS: Thirty-seven of 480 articles identified between 1969 and 2016 met the eligibility criteria. Twenty-nine of these contributed primary data on hearing outcomes and 20 on neurodevelopmental outcomes (12 of the 37 studies contributed data on both). Cumulative incidence of sensorineural hearing loss with follow-up to at least 5 years was 7% to 11%, which is more than healthy controls but less than children with symptomatic congenital CMV (34%-41%). The onset, course, and severity of hearing loss was variable with no reliable virological prognostic marker. In comparison to controls, children with asymptomatic congenital CMV did not perform worse than controls in neurodevelopmental assessments and performed better than children with symptomatic congenital CMV. CONCLUSIONS: Studies show children with asymptomatic congenital CMV are at increased risk of developing hearing loss but perform equally well on neurodevelopmental assessments when compared with healthy controls. There is no reliable virological marker to determine which infants will develop sequelae. Regular follow-up until school entry is supported by the literature.
Testing the niche-breadth-range-size hypothesis: habitat specialization vs. performance in Australian alpine daisies
Relatively common species within a clade are expected to perform well across a wider range of conditions than their rarer relatives, yet experimental tests of this "niche-breadth-range-size" hypothesis remain surprisingly scarce. Rarity may arise due to trade-offs between specialization and performance across a wide range of environments. Here we use common garden and reciprocal transplant experiments to test the niche-breadth-range-size hypothesis, focusing on four common and three rare endemic alpine daisies (Brachyscome spp.) from the Australian Alps. We used three experimental contexts: (1) alpine reciprocal seedling experiment, a test of seedling survival and growth in three alpine habitat types differing in environmental quality and species diversity; (2) warm environment common garden, a test of whether common daisy species have higher growth rates and phenotypic plasticity, assessed in a common garden in a warmer climate and run simultaneously with experiment 1; and (3) alpine reciprocal seed experiment, a test of seed germination capacity and viability in the same three alpine habitat types as in experiment 1. In the alpine reciprocal seedling experiment, survival of all species was highest in the open heathland habitat where overall plant diversity is high, suggesting a general, positive response to a relatively productive, low-stress environment. We found only partial support for higher survival of rare species in their habitats of origin. In the warm environment common garden, three common daisies exhibited greater growth and biomass than two rare species, but the other rare species performed as well as the common species. In the alpine reciprocal seed experiment, common daisies exhibited higher germination across most habitats, but rare species maintained a higher proportion of viable seed in all conditions, suggesting different life history strategies. These results indicate that some but not all rare, alpine endemics exhibit stress tolerance at the cost of reduced growth rates in low-stress environments compared to common species. Finally, these findings suggest the seed stage is important in the persistence of rare species, and they provide only weak support at the seedling stage for the niche-breadth-range-size hypothesis.
Study of the Huntington's disease IT-15 gene in different ethnic groups in Ecuador.
This study aims to establish the current state of the IT-15 (HTT) gene in different Ecuadorian ethnic groups and patients by determining CAG triplet repeats, compared with the ethnicity of individuals. A total of 412 individuals were studied using nested polymerase chain reaction and Sanger sequencing: 75 individuals were indigenous (Kichwas), 211 mestizos, and 65 Afro-Ecuadorians. We included 31 patients who were clinically diagnosed with Huntington's disease (HD) and relatives of the affected patients (n = 30). Moreover, we correlated the presence of HD in Ecuadorian patients with 46 genetic ancestry-informative insertion-deletion polymorphic markers. We found that 77.20% had <28 CAG repetitions, 18.80% had mutable alleles, 2.27% had incomplete penetrance, and 1.70% reflected >39 repetitions. The average of CAG repetitions was 24 ± 3 for indigenous people; 28 ± 2 for mestizos; and 24 ± 3.2 repetitions for the Afro-Ecuadorians. The ancestral component showed that the main ancestry corresponded to Native Americans (0.873) and European ascendants (0.145), Africans were less represented in the evaluated population (0.018). There was a significant difference between the number of CAG repeats in mestizos and indigenous people (P < .01), suggesting that the Ecuadorian mestizo population has a risk factor for the gene mutation.
Plasma Proteome Association and Catalytic Activity of Stealth Polymer-Grafted Iron Oxide Nanoparticles
(WILEY-V C H VERLAG GMBH, 2017-09-27)
Polyethylene glycol (PEG) is widely used as an antifouling and stealth polymer in surface engineering and nanomedicine. However, recent research has revealed adverse effects of bioaccumulation and immunogenicity following the administration of PEG, prompting this proteomic examination of the plasma protein coronae association with superparamagnetic iron oxide nanoparticles (IONPs) grafted with brushed PEG (bPEG) and an alternative, brushed phosphorylcholine (bPC). Using label-free quantitation by liquid chromatography tandem-mass spectrometry, this study determines protein abundances for the in vitro hard coronae of bare, bPC-, and bPEG-grafted IONPs in human plasma. This study also shows unique protein compositions in the plasma coronae of each IONP, including enrichment of coagulation factors and immunogenic complement proteins with bPEG, and enhanced binding of apolipoproteins with bPC. Functional analysis reveals that plasma protein coronae elevate the horseradish peroxidase-like activities of the bPC- and bPEG-IONPs by approximately twofold, an effect likely mediated by the diverse composition and physicochemical properties of the polymers as well as their associated plasma proteins. Taken together, these observations support the rational design of stealth polymers based on a quantitative understanding of the interplay between IONPs and the plasma proteome, and should prove beneficial for the development of materials for nanomedicine, biosensing, and catalysis.
Visual methods in health dialogues: A qualitative study of public health nurse practice in schools
AIMS: We aimed to explore how using visual methods might improve or complicate the dynamics of the health dialogue between public health nurses (PHNs) and school pupils. This was done from the perspective of PHNs, specifically examining how they understood their role and practice as a PHN and the application of visual methods in this practice. BACKGROUND: The health dialogue is a method used by PHNs in school nursing in Norway. In this practice, there can be communicative barriers between pupils and PHNs. Investigating how PHNs understand their professional practice can lead to ways of addressing these communicative barriers, which can affect pupil satisfaction and achievement of health-related behaviours in the school context. Specifically, the use of visual methods by PHNs may address these communicative barriers. DESIGN: The research design was qualitative, using focus groups combined with visual methods. METHODS: We conducted focus group interviews using a semi-structured discussion guide and visual methods with five groups of PHNs (n = 31) working in northern Norwegian school health services. The data were collected during January and February 2016. Discussions were audio recorded, transcribed and coded into themes and sub-themes using systematic text condensation and drawings were analysed using interpretive engagement, a method of visual analysis. FINDINGS: Drawings and focus group discussions showed that PHNs perceived their professional practice as primarily a relational praxis. The PHNs used a variety of visual methods as part of the health dialogue with school pupils. This active use of visualization worked to build and strengthen relations when words were inadequate and served to enhance the flexible and relational practice employed by the PHNs. CONCLUSIONS: PHNs used different kinds of visualization methods to establish relations with school pupils, especially when verbalization by the pupils was difficult. PHNs were aware of both the benefits and challenges of using visualization with school pupils in health education. We recommend the use of visual methods in schools because they are useful for PHNs, other health professionals and teachers working with children and young people in developing relations, particularly where verbal communication may be a challenge.
Clinical outcomes after local field conformal reirradiation of patients with retropharyngeal nodal metastasis
BACKGROUND: The purpose of this study was to present our experience with retropharyngeal node reirradiation using highly conformal radiotherapy (RT). METHODS: A retrospective screen of 2504 consecutively irradiated patients with head and neck malignancies between 2005 and 2015 identified 19 patients who underwent reirradiation for retropharyngeal node metastasis. Clinical and toxicity outcomes were assessed in these patients. RESULTS: Thirteen patients (68%) had squamous cell carcinoma. Eleven patients (58%) received conventionally fractionated intensity-modulated radiotherapy (IMRT) or proton therapy, and 8 patients (42%) received single-fractionated or hypofractionated stereotactic RT. Fourteen patients (74%) received chemotherapy. Median follow-up was 14.7 months. The 1-year local control, locoregional control, overall survival, and progression-free survival rates were 100%, 94%, 92%, and 92%, respectively. Three patients (16%) experienced acute grade 3 toxicity and occurred in those treated with IMRT. There was no late grade ≥3 toxicity. CONCLUSION: Retropharyngeal node reirradiation with conformal therapy is well tolerated and associated with excellent short-term disease control.
Role of art centres for Aboriginal Australians living with dementia in remote communities
OBJECTIVE: To explore the role art centres in remote communities play for Aboriginal and Torres Strait Islander Australians living with dementia. METHODS: A comprehensive literature search was undertaken, with no restrictions on articles regarding year of publication. RESULTS: Art programmes have been found to be of benefit to both people living with dementia and their carers, particularly when programmes are administered in environments that are culturally revered. Findings indicate remote art centres play a key role in maintaining traditions, culture and practices unique to Aboriginal and Torres Strait Islanders, but there is a gap in knowledge regarding how they cater for the needs of people with dementia. CONCLUSION: Addressing this gap will be helpful in remote areas where prevalence of dementia is up to five times that of non-Aboriginal people, and there are limited health and support services. Further research is required to explore strengths and gaps of current practices.
Filling the gaps and finding our way: family carers navigating the healthcare system to access physical health services for the people they care for.
AIMS AND OBJECTIVES: To elicit the perspectives of carers of people with mental illness regarding access to, and experience with, physical healthcare services for mental health consumers. BACKGROUND: People diagnosed with mental illness have increased risks of physical illness and earlier death, problems able to be addressed through better physical health services. Carers of people with mental illness play a significant role in the mental healthcare system yet research examining their views is lacking. DESIGN: Qualitative exploratory. METHODS: In-depth interviews were conducted with 13 mental health carers. They were asked to describe their views and experiences pertaining to the physical health and availability of physical health care for the people they care for. Data were analysed using the framework of Braun and Clarke. RESULTS: Analysis of carer responses identified two important themes: responsiveness and access, and a shortage of care coordination. Carers felt alienated from physical healthcare providers and were compelled to fill gaps in available care through persistence in ensuring access to physical healthcare services. CONCLUSIONS: The findings identify carers as key stakeholders in the physical health care for the people they care for. Their involvement in accessing and coordinating care provides vital perspective on health service capacity, which requires further consideration in the practice and research domains. RELEVANCE TO CLINICAL PRACTICE: Carers of people diagnosed with mental illness are crucial to the effective delivery of mental health services. Their perspectives must be central to their research agenda and contribute to the development of initiatives to improve clinical practice and promote improved physical health care.
Fifteen-year groin hernia trends in Australia: the era of minimally invasive surgeons
BACKGROUND: Groin hernia repairs (GHRs) are among the commonest general surgical procedures in the Western population. The introduction of minimally invasive surgery has prompted the development of laparoscopic totally extraperitoneal and trans-abdominal preperitoneal hernia repairs. We aimed to determine the hernia treatment trends in Australia over the last 15 years. METHODS: Using Medicare Benefit Schedule data, we categorized the number of laparoscopic and open hernia repairs between 2000 and 2015 in Australia. Population data were collected from the Australian Bureau of Statistics. Hernia repair rates were standardized by age, gender and location. RESULTS: During the study period, a total of 324 618 GHRs were performed on adult patients in Australia, 43% by a laparoscopic method. While there was a slight yearly increase in overall total GHRs performed, laparoscopic surgeries increased by 3.1 per 100 000 population every year (95% CI: 2.9-3.3) while open surgeries declined yearly by 2.6 per 100 000 population (95% CI: 2.4-2.8). From the available data, there appears to be a crossover point in 2011/2012 where the laparoscopic hernia repair became more frequent. Considerable state and gender-based trends exist. CONCLUSIONS: The use of laparoscopic GHRs has increased considerably over the last 15 years. Despite the increased use, significant state-based and gender discrepancies were observed. Our data offer insight to the public sector and the respective healthcare-related expenditures pertaining to laparoscopic hernia repair.
Is there a practical role for a virtual bone biopsy using high-resolution imaging of bone in patients with chronic kidney disease?
Renal osteodystrophy (ROD) refers to alterations in bone turnover, mineralisation, mass and microarchitecture in patients with chronic kidney disease (CKD) and represents the skeletal component of 'CKD-mineral and bone disorder'. Changes in bone structure lead to impaired bone quality, compromised bone strength and increased susceptibility to fractures with associated significant morbidity, mortality and financial cost. Diagnosis and management of ROD is hindered by the inadequacy of currently available diagnostic methods to interpret the complex pathophysiology. Bone biopsy, the perceived gold standard test to assess ROD, is invasive and suboptimal for disease screening and management in routine clinical practice. High-resolution imaging, such as high-resolution peripheral quantitative computed tomography and high-resolution magnetic resonance imaging provide accurate non-invasive quantification of bone microarchitecture and facilitate assessment of mechanical competence of bone, correlating with skeletal fragility. We discuss the potential for these imaging techniques in patients with CKD to provide quantification and assessment of bone structure and strength. When used in conjunction with serum biomarkers, these investigative tools may provide a non-invasive diagnostic virtual bone biopsy.
Is there a role for newer biomarkers in chronic kidney disease-mineral and bone disorder management?
The current management of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) relies largely on clinical judgement and assessment of biochemical parameters including serum calcium, phosphate and intact parathyroid hormone concentrations. In the past two decades, there has been a leap in the understanding of the pathophysiology of CKD-MBD, leading to the discovery of novel biomarkers. The potential utility of these markers in this clinical setting is an area of intense investigation. In the absence of any guidelines aiding the clinician's understanding and application of these markers, we summarise the current available literature surrounding fibroblast growth factor-23, α-Klotho, sclerostin and serum calcification propensity testing and their respective assays in the context of CKD-MBD management.
MUC13 overexpression in renal cell carcinoma plays a central role in tumor progression and drug resistance
Metastatic renal cell carcinoma is a largely incurable disease, and existing treatments targeting angiogenesis and tyrosine kinase receptors are only partially effective. Here we reveal that MUC13, a cell surface mucin glycoprotein, is aberrantly expressed by most renal cell carcinomas, with increasing expression positively correlating with tumor grade. Importantly, we demonstrated that high MUC13 expression was a statistically significant independent predictor of poor survival in two independent cohorts, particularly in stage 1 cancers. In cultured renal cell carcinoma cells MUC13 promoted proliferation and induced the cell cycle regulator, cyclin D1, and inhibited apoptosis by inducing the anti-apoptotic proteins, BCL-xL and survivin. Silencing of MUC13 expression inhibited migration and invasion, and sensitized renal cancer cells to killing by the multi-kinase inhibitors used clinically, sorafenib and sunitinib, and reversed acquired resistance to these drugs. Furthermore, we demonstrated that MUC13 promotion of renal cancer cell growth and survival is mediated by activation of nuclear factor κB, a transcription factor known to regulate the expression of genes that play key roles in the development and progression of cancer. These results show that MUC13 has potential as a prognostic marker for aggressive early stage renal cell cancer and is a plausible target to sensitize these tumors to therapy.
Bone turnover markers and bone mineral density in healthy mother-daughter pairs from South India
Bone turnover markers (BTMs) provide important insights into the dynamics of bone remodelling and are subjected to preanalytical and ethnic variations in addition to influence of genetic and environmental factors. AIM/OBJECTIVES: To derive ethnicity specific reference range for BTMs and to study their correlation with Bone Mineral Density (BMD) in a cohort of healthy postmenopausal women and their premenopausal daughters and to look at the impact of maternal bone mineral status on daughters bone health. MATERIAL AND METHODS: This community based cross sectional study included 300 subjects (150 mother-daughter pairs). Demographic details were collected. Fasting blood and a second void morning urine samples were obtained for measurement of BTMs (sCTX, sPTNP1, sOC and urine DPD respectively) and bone mineral parameters. BMD was measured by DXA scan. RESULTS: Osteoporosis was seen in 44·7% of the postmenopausal women. Ethnicity specific reference ranges of BTMs were derived for the study population. Significant inverse correlation was found between all BTMs (except urine DPD) and BMD(P < 0·05). Daughters of mothers with osteoporosis at spine and femoral neck had lower BMD, compared to daughters of mothers without osteoporosis(P = 0·03 & 0·05). CONCLUSION: Apart from deriving the ethnicity specific reference range for BTMs and finding a significant inverse correlation between BTM and BMD, this study found significantly lower BMD in daughters of mothers with osteoporosis at spine and femoral neck implicating the probable interplay of genetic, epigenetic and similar environmental factors.
Tropical Drosophila pandora carry Wolbachia infections causing cytoplasmic incompatibility or male killing
Wolbachia infections have been described in several Drosophila species, but relatively few have been assessed for phenotypic effects. Cytoplasmic incompatibility (CI) is the most common phenotypic effect that has been detected, while some infections cause male killing or feminization, and many Wolbachia infections have few host effects. Here, we describe two new infections in a recently described species, Drosophila pandora, one of which causes near-complete CI and near-perfect maternal transmission (the "CI" strain). The other infection is a male killer (the "MK" strain), which we confirm by observing reinitiation of male production following tetracycline treatment. No incompatibility was detected in crosses between CI strain males and MK strain females, and rare MK males do not cause CI. Molecular analyses indicate that the CI and MK infections are distantly related and the CI infection is closely related to the wRi infection of Drosophila simulans. Two population surveys indicate that all individuals are infected with Wolbachia, but the MK infection is uncommon. Given patterns of incompatibility among the strains, the infection dynamics is expected to be governed by the relative fitness of the females, suggesting that the CI infection should have a higher fitness. This was evidenced by changes in infection frequencies and sex ratios in population cages initiated at different starting frequencies of the infections.
'That red flag on your file': misinterpreting physical symptoms as mental illness.
AIMS AND OBJECTIVES: To ascertain the views and experiences of mental health consumers regarding the availability and quality of care and treatment received for their physical health needs. BACKGROUND: People diagnosed with mental illness have higher occurrence of physical health problems. Responsive health care services are crucial for prevention and management of physical health problems, and for reducing disparities in health between people diagnosed with mental illness and those who are not. There is limited research giving voice to consumer perspectives on their experiences with health care providers. DESIGN: Exploratory qualitative. METHODS: Focus group interviews with mental health consumers accessed via a consumer network group in a region of Australia (n = 31). All interview audio recordings were transcribed professionally. Interviews were thematically analysed. RESULTS: The main themes were: symptomising; failure to act and alertness to prejudice. The first two themes were consumer perceptions of the actions and behaviours of health professionals, and the third describes consumer responses to these behaviours and actions. Consumers described increased risks of illness and death because of undiagnosed physical illness despite their physical health advice-seeking as the reason for the health consultation. CONCLUSION: Health care providers' non-recognition of physical health problems presents a clear example of a significant and potentially life threatening health inequity. The service provider responses described by participants suggest that mental health consumers' physical health needs may not be taken seriously. RELEVANCE TO CLINICAL PRACTICE: Clinicians need to take seriously the physical health needs and concerns of people with mental illness. Nurses can play a crucial role in the prevention of diagnostic overshadowing as part of a broader direction of balancing biomedical perspectives with other approaches to health care.
Participative mental health consumer research for improving physical health care: An integrative review.
People with mental illness have a significantly lower life expectancy and higher rates of chronic physical illnesses than the general population. Health care system reform to improve access and quality is greatly needed to address this inequity. The inclusion of consumers of mental health services as co-investigators in research is likely to enhance service reform. In light of this, the current paper reviews mental health consumer focussed research conducted to date, addressing the neglect of physical health in mental health care and initiatives with the aim of improving physical health care. The international literature on physical healthcare in the context of mental health services was searched for articles, including mental health consumers in research roles, via Medline, CINAHL and Google Scholar, in October 2015. Four studies where mental health consumers participated as researchers were identified. Three studies involved qualitative research on barriers and facilitators to physical health care access, and a fourth study on developing technologies for more effective communication between GPs and patients. This review found that participatory mental health consumer research in physical health care reform has only become visible in the academic literature in 2015. Heightened consideration of mental health consumer participation in research is required by health care providers and researchers. Mental health nurses can provide leadership in increasing mental health consumer research on integrated care directed towards reducing the health gap between people with and without mental illness.
Gene expression profiling of reproductive meristem types in early rice inflorescences by laser microdissection
In rice, inflorescence architecture is established at early stages of reproductive development and contributes directly to grain yield potential. After induction of flowering, the complexity of branching, and therefore the number of seeds on the panicle, is determined by the activity of different meristem types and the timing of transitions between them. Although some of the genes involved in these transitions have been identified, an understanding of the network of transcriptional regulators controlling this process is lacking. To address this we used a precise laser microdissection and RNA-sequencing approach in Oryza sativa ssp. japonica cv. Nipponbare to produce quantitative data that describe the landscape of gene expression in four different meristem types: the rachis meristem, the primary branch meristem, the elongating primary branch meristem (including axillary meristems), and the spikelet meristem. A switch in expression profile between apical and axillary meristem types followed by more gradual changes during transitions in axillary meristem identity was observed, and several genes potentially involved in branching were identified. This resource will be vital for a mechanistic understanding of the link between inflorescence development and grain yield.
A randomised controlled trial comparing meat-based with human cadaveric models for teaching ultrasound-guided regional anaesthesia
The aim of this prospective, blinded, randomised controlled study was to compare novices' acquisition of the technical skills of ultrasound-guided regional anaesthesia using either a meat phantom model or fresh-frozen human cadavers. The primary outcome was the time taken to successfully perform an ultrasound-guided sciatic nerve block on a cadaver; secondary outcomes were the cumulative score of errors, and best image quality of the sciatic nerve achieved. After training, the median (IQR [range]) time taken to perform the block was 311(164-390 [68-600]) s in the meat model trained group and 210 (174-354 [85-600]) s in the fresh-frozen cadaver trained group (p = 0.24). Participants made a median (IQR [range]) of 18 (14-33 [8-55]) and 15 (12-22 [8-44]) errors in the two groups respectively (p = 0.39). The image quality score was also not different, with a median (IQR [range]) of 62.5 (59.4-65.6 [25.0-100.0])% vs 62.5 (62.5-75.0 [25.0-87.5])% respectively (p = 0.58). The training and deliberate feedback improved all participants' block performance, the median (IQR [range]) times being 310 (206-532 [110-600]) s before and 240 (174-354 [85-600]) s after training (p = 0.02). We conclude that novices taught ultrasound scanning and needle guidance skills using an inexpensive and easily constructed meat model perform similarly to those trained on a cadaveric model.
Lysine acetylation of the Mycobacterium tuberculosis HU protein modulates its DNA binding and genome organization
Nucleoid-associated protein HU, a conserved protein across eubacteria is necessary for maintaining the nucleoid organization and global regulation of gene expression. Mycobacterium tuberculosis HU (MtHU) is distinct from the other orthologues having 114 amino acid long carboxyl terminal extensions with a high degree of sequence similarity to eukaryotic histones. In this study, we demonstrate that the DNA binding property of MtHU is regulated by posttranslational modifications akin to eukaryotic histones. MtHU purified from M. tuberculosis cells is found to be acetylated on multiple lysine residues unlike the E. coli expressed recombinant protein. Using coimmunoprecipitation assay, we identified Eis as one of the acetyl transferases that interacts with MtHU and modifies it. Although Eis is known to acetylate aminoglycosides, the kinetics of acetylation showed that its protein acetylation activity on MtHU is robust. In vitro Eis modified MtHU at various lysine residues, primarily those located at the carboxyl terminal domain. Acetylation of MtHU caused reduced DNA interaction and alteration in DNA compaction ability of the NAP. Over-expression of the Eis leads to hyperacetylation of HU and decompaction of genome. These results provide first insights into the modulation of the nucleoid structure by lysine acetylation in bacteria.
Wide allelic heterogeneity with predominance of large IDS gene complex rearrangements in a sample of Mexican patients with Hunter syndrome
Hunter syndrome or mucopolysaccharidosis type II (MPSII) is caused by pathogenic variants in the IDS gene. This is the first study that examines the mutational spectrum in 25 unrelated Mexican MPSII families. The responsible genotype was identified in 96% of the families (24/25) with 10 novel pathogenic variants: c.133G>C, c.1003C>T, c.1025A>C, c.463_464delinsCCGTATAGCTGG, c.754_767del, c.1132_1133del, c.1463del, c.508-1G>C, c.1006+1G>T and c.(-217_103del). Extensive IDS gene deletions were identified in four patients; using DNA microarray analysis two patients showed the loss of the entire AFF2 gene, and epilepsy developed in only one of them. Wide allelic heterogeneity was noted, with large gene alterations (e.g. IDS/IDSP1 gene inversions, partial to extensive IDS deletions, and one chimeric IDS-IDSP1 allele) that occurred at higher frequencies than previously reported (36% vs 18.9-29%). The frequency of carrier mothers (80%) is consistent with previous descriptions (>70%). Carrier assignment allowed molecular prenatal diagnoses. Notably, somatic and germline mosaicism was identified in one family, and two patients presented thrombocytopenic purpura and pancytopenia after idursulfase enzyme replacement treatment. Our findings suggest a wide allelic heterogeneity in Mexican MPSII patients; DNA microarray analysis contributes to further delineation of the resulting phenotype for IDS and neighboring loci deletions.
Examining the N400m in affectively negative sentences: A magnetoencephalography study
Magnetoencephalography was used to examine the effect on the N400m of reading words that create emotional violations in sentences. The beginnings of the sentences were affectively negative and were completed with either a negative congruous, positive incongruous, or neutral incongruous adjective (e.g., "My mother was killed and I felt bad/great/normal"). The task conditions were also manipulated to favor semantic over affective processing. Compared to the sentences with the congruous negative adjectives, the results of sensor space analysis showed that there was an N400m effect with the sentences with the neutral but not positive adjectives, despite both types of sentences containing an emotional violation. Source localization results showed a similar pattern where the sentences with the incongruous positive versus congruous negative adjectives showed no significant N400m effect in the temporal and frontal areas examined, but the sentences with the incongruous neutral versus incongruous positive adjectives in the temporal areas did, particularly the left middle temporal gyrus. These results suggest that (a) the N400m effect was likely to be caused by the incongruous neutral adjectives being comparatively harder to integrate into a negative emotional context than the incongruous positive ones, (b) emotional context created by the negative sentence stems caused deeper semantic processing of the incongruous positive adjectives to be bypassed, and (c) negative affective context was generated from reading the sentences even in task conditions where it has not been generated with isolated words.
Embedding a physical health nurse consultant within mental health services: Consumers' perspectives.
The life expectancy of people living with mental illness is significantly shorter than that of the rest of the population. Despite the profound impact of physical health issues on both quality of life and life expectancy, the perspectives of mental health consumers have yet to be thoroughly explored. Furthermore, research has focused far more on describing barriers than on identifying solutions. This paper reports on findings from a qualitative exploratory research study, with the aim to examine the potential role of a specialist nurse with advanced physical health-care skills. Focus groups were conducted with 31 consumers. Data were analysed thematically. The concept of a role like this was supported; however, participants stressed: (i) the importance of integration between health professionals and various components of the health-care system; and (ii) the need for culture change for nurses to work from a less medically-dominated approach. Previous research literature suggests that a nursing position dedicated to physical health care and coordination might produce positive outcomes for mental health consumers. The findings from the current research project emphasize the need for consumers to be identified as key stakeholders in a solution-focused approach to improved physical health care for mental health consumers.
Evaluating a Muscle Ultrasound Education Program: Theoretical Knowledge, Hands-on Skills, Reliability, and Satisfaction of Critical Care Physiotherapists.
(Elsevier BV, 2021-09)
Objective: To evaluate learning results of critical care physiotherapists participating in a muscle ultrasound (MUS) educational program. Design: Cross-sectional study. Setting: A custom-made 20-hour MUS course was performed over a 2-week time period, including knobs familiarization, patient positioning, anatomic landmarks, image acquisition, and limb muscle measurements. Participants: Nineteen critical care physiotherapists with little to no prior experience in ultrasound (N=19). Interventions: Not applicable. Main Outcome Measures: Theoretical knowledge, hands-on skills acquisition, and satisfaction were assessed. Inter- and intrarater reliability on landmarks, thickness, and pennation angle of quadriceps between participants was evaluated using intraclass correlation coefficients (ICCs). Reliability among instructors measured prior to the course was also reported as a reference. Results: The percentage score (mean±SD) of knowledge questionnaires was 69±11 (pre-course), 89±10 (post-course), and 92±9 (hands-on skills). Course satisfaction scores ranged from 90%-100%. Pooled interrater reliability of participants (median ICC [interquartile range]) was good (0.70 [0.59-0.79]) for thickness, moderate (0.47 [0.46-0.92]) for landmarks, and absent (0.00 [0.00-0.05]) for pennation angle and the intrarater reliability was good (0.76 [0.51-0.91]) for thickness and weak (0.35 [0.29-0.52]) for pennation angle. Interrater ICC values for instructors were excellent (0.90) for thickness, good (0.67) for landmarks, and moderate (0.41) for pennation angle and intrarater ICC values were excellent (0.94) for thickness and good (0.75) for pennation angle. Conclusions: Although our sample was quite small and homogeneous, increased theoretical knowledge, high hands-on performance acquisition, and good satisfaction of physiotherapists were observed. Reliability was moderate to excellent for thickness and landmarks and absent to weak for pennation angle. Landmarking and pennation angle remain challenges for physiotherapist training in the application of MUS. Further studies are needed to identify variables that could modify reliability during MUS training.
A Rare Case of Extra-Gonadal Oestrogen-Secreting Choriocarcinoma in a Male.
(SMC Media, 2021)
This report describes a rare case of an extra-gonadal oestrogen-secreting tumour in a male patient. An otherwise healthy 60-year-old man presented to our hospital with a 3-month history of shortness of breath and weight loss. Blood panels and histology supported the diagnosis of an oestrogen-secreting choriocarcinoma. Unfortunately, the patient died soon after his diagnosis. The highlighting features of this case are: (1) the difficulty of confirming a diagnosis in a rapidly deteriorating patient; (2) the rarity of oestrogen-secreting extra-gonadal tumours in males; and (3) the aggressive rate of tumour progression seen on sequential imaging. LEARNING POINTS: Extra-gonadal oestrogen-secreting tumours in males are rare, but early empiric chemotherapy can be of benefit if this diagnosis is suspected.Tumour progression can be rapid, and so prompt referral to oncology services is critical for emergent management of the condition.Full endocrine blood panels including oestrogen, β human chorionic gonadotrophin and α fetoprotein are useful to help diagnose the condition.
Total Body Sodium Balance in Chronic Kidney Disease
(HINDAWI LTD, 2021-09-22)
Excess sodium intake is a leading but modifiable risk factor for mortality, with implications on hypertension, inflammation, cardiovascular disease, and chronic kidney disease (CKD). This review will focus mainly on the limitations of current measurement methods of sodium balance particularly in patients with CKD who have complex sodium physiology. The suboptimal accuracy of sodium intake and excretion measurement is seemingly more marked with the evolving understanding of tissue (skin and muscle) sodium. Tissue sodium represents an extrarenal influence on sodium homeostasis with demonstrated clinical associations of hypertension and inflammation. Measurement of tissue sodium has been largely unexplored in patients with CKD. Development and adoption of more comprehensive and dynamic assessment of body sodium balance is needed to better understand sodium physiology in the human body and explore therapeutic strategies to improve the clinical outcomes in the CKD population.
Activated osteoarthritis following immune checkpoint inhibitor treatment: an observational study
(BMJ PUBLISHING GROUP, 2021-09-01)
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but can result in toxicities, known as immune-related adverse events (irAEs), due to a hyperactivated immune system. ICI-related inflammatory arthritis has been described in literature, but herewith we introduce and characterize post-ICI-activated osteoarthritis (ICI-aOA). We conducted a multicenter, retrospective, observational study of patients with cancer treated with ICIs and diagnosed with ICI-aOA by a rheumatologist. ICI-aOA was defined by (1) an increase in non-inflammatory joint pain after ICI initiation, (2) in joints characteristically affected by osteoarthritis, and (3) lack of inflammation on exam. Cases were graded using the Common Terminology Criteria for Adverse Events (CTCAE) V.6.0 rubric for arthralgia. Response Evaluation Criteria in Solid Tumors V.1.1 (v.4.03) guidelines determined tumor response. Results were analyzed using χ2 tests of association and multivariate logistic regression. Thirty-six patients had ICI-aOA with a mean age at time of rheumatology presentation of 66 years (51-81 years). Most patients had metastatic melanoma (10/36, 28%) and had received a PD-1/PD-L1 inhibitor monotherapy (31/36, 86%) with 5/36 (14%) combination therapy. Large joint involvement (hip/knee) was noted in 53% (19/36), small joints of hand 25% (9/36), and spine 14% (5/36). Two-thirds (24/36) suffered multiple joint involvement. Three of 36 (8%) had CTCAE grade 3, 14 (39%) grade 2 and 19 (53%) grade 1 manifestations. Symptom onset ranged from 6 days to 33.8 months with a median of 5.2 months after ICI initiation; five patients suffered from ICI-aOA after ICI cessation (0.6, 3.5, 4.4, 7.3, and 15.4 months after ICI cessation). The most common form of therapy was intra-articular corticosteroid injections only (15/36, 42%) followed by non-steroidal anti-inflammatory drugs only (7/36, 20%). Twenty patients (56%) experienced other irAEs, with rheumatic and dermatological being the most common. All three patients with high-grade ICI-aOA also had another irAE diagnosis at some point after ICI initiation. ICI-aOA should be recognized as an adverse event of ICI immunotherapy. Early referral to a rheumatologist can facilitate the distinction between ICI induced inflammatory arthritis from post-ICI mechanical arthropathy, the latter of which can be managed with local therapy that will not compromise ICI efficacy.
Systematic Review and Meta-Analysis of Inflammatory Bowel Disease Adverse Events with Anti-Interleukin 17A Agents and Tumor Necrosis Factor Inhibitors in Rheumatic Disease and Skin Psoriasis
INTRODUCTION: The aim of this work is to perform a systematic review and meta-analysis of anti-tumor necrosis factor (anti-TNF) and anti-interleukin-17 (anti-IL-17) trials for spondyloarthritis, psoriatic arthritis, and psoriasis comparing rates of inflammatory bowel disease (IBD) events compared to placebo. METHODS: MEDLINE, EMBASE, and The Cochrane Library were searched for double-blind, randomized placebo-controlled anti-TNF and anti-IL-17 trials of included diseases. Inflammatory bowel disease events from the RCT period were pooled and meta-analyzed using statistical methods suitable for low-event-rate meta-analysis (Peto's, Mantel-Haenszel, hypergeometric-normal model, and Shuster-Guo-Skyler). When observed data were insufficient, we performed an exploratory sensitivity analysis to compare methods. RESULTS: We identified 9551 original papers, and included 96 publications: 65 anti-TNF and 31 anti-IL-17 trials, containing 21 new and 12 flare IBD events in 28,209 participants. New IBD on anti-IL-17 occurred 0.23/100 patient-years (PY) in psoriasis, 0.61/100 PY in PsA and 1.63/100 PY in spondyloarthritis, rates similar to observational cohorts, and less commonly on anti-TNF (0/100 PY, 0/100 PY, 0.32/100 PY, respectively). No evidence of difference between groups was found, with wide CI from many pooled counts of zero, especially in placebo arms. CONCLUSIONS: IBD events were rare, occurring at rates similar to biologic-naive groups. We could not find statistically significant differences in risk of new or recurrent IBD between treatment and control groups using selected meta-analytical methods for low event rate scenarios. Meta-analyses of this topic require more IBD events, ideally without pooling heterogeneous groups. Larger, thoroughly reported trials with systematic and detailed safety reporting are required to improve risk estimation and to make accurate inferences.
Immediate effect of the COVID-19 pandemic on patient health, health-care use, and behaviours: results from an international survey of people with rheumatic diseases
Background: The impact and consequences of the COVID-19 pandemic on people with rheumatic disease are unclear. We developed the COVID-19 Global Rheumatology Alliance Patient Experience Survey to assess the effects of the COVID-19 pandemic on people with rheumatic disease worldwide. Methods: Survey questions were developed by key stakeholder groups and disseminated worldwide through social media, websites, and patient support organisations. Questions included demographics, rheumatic disease diagnosis, COVID-19 diagnosis, adoption of protective behaviours to mitigate COVID-19 exposure, medication access and changes, health-care access and communication with rheumatologists, and changes in employment or schooling. Adults age 18 years and older with inflammatory or autoimmune rheumatic diseases were eligible for inclusion. We included participants with and without a COVID-19 diagnosis. We excluded participants reporting only non-inflammatory rheumatic diseases such as fibromyalgia or osteoarthritis. Findings: 12 117 responses to the survey were received between April 3 and May 8, 2020, and of these, 10 407 respondents had included appropriate age data. We included complete responses from 9300 adults with rheumatic disease (mean age 46·1 years; 8375 [90·1%] women, 893 [9·6%] men, and 32 [0·3%] participants who identified as non-binary). 6273 (67·5%) of respondents identified as White, 1565 (16·8%) as Latin American, 198 (2·1%) as Black, 190 (2·0%) as Asian, and 42 (0·5%) as Native American or Aboriginal or First Nation. The most common rheumatic disease diagnoses included rheumatoid arthritis (3636 [39·1%] of 9300), systemic lupus erythematosus (2882 [31·0%]), and Sjögren's syndrome (1290 [13·9%]). Most respondents (6921 [82·0%] of 8441) continued their antirheumatic medications as prescribed. Almost all (9266 [99·7%] of 9297) respondents adopted protective behaviours to limit SARS-CoV-2 exposure. A change in employment status occurred in 2524 (27·1%) of 9300) of respondents, with a 13·6% decrease in the number in full-time employment (from 4066 to 3514). Interpretation: People with rheumatic disease maintained therapy and followed public health advice to mitigate the risks of COVID-19. Substantial employment status changes occurred, with potential implications for health-care access, medication affordability, mental health, and rheumatic disease activity. Funding: American College of Rheumatology.