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1.
Bioelectron Med ; 10(1): 13, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38825695

ABSTRACT

BACKGROUND: Blue light activates melanopsin, a photopigment that is expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs). The axons of ipRGCs converge on the optic disc, which corresponds to the physiological blind spot in the visual field. Thus, a blue light stimulus aligned with the blind spot captures the ipRGCs axons at the optic disc. This study examined the potential changes in choroidal thickness and axial length associated with blue light stimulation of melanopsin-expressing ipRGCs at the blind spot. It was hypothesized that blue light stimulation at the blind spot in adults increases choroidal thickness. METHODS: The blind spots of both eyes of 10 emmetropes and 10 myopes, with a mean age of 28 ± 6 years (SD), were stimulated locally for 1-minute with blue flickering light with a 460 nm peak wavelength. Measurements of choroidal thickness and axial length were collected from the left eye before stimulation and over a 60-minute poststimulation period. At a similar time of day, choroidal thickness and axial length were measured under sham control condition in all participants, while a subset of 3 emmetropes and 3 myopes were measured after 1-minute of red flickering light stimulation of the blind spot with a peak wavelength of 620 nm. Linear mixed model analyses were performed to examine the light-induced changes in choroidal thickness and axial length over time and between refractive groups. RESULTS: Compared with sham control (2 ± 1 µm, n = 20) and red light (-1 ± 2 µm, n = 6) stimulation, subfoveal choroidal thickness increased within 60 min after blue light stimulation of the blind spot (7 ± 1 µm, n = 20; main effect of light, p < 0.001). Significant choroidal thickening after blue light stimulation occurred in emmetropes (10 ± 2 µm, p < 0.001) but not in myopes (4 ± 2 µm, p > 0.05). Choroidal thickening after blue light stimulation was greater in the fovea, diminishing in the parafoveal and perifoveal regions. There was no significant main effect of light, or light by refractive error interaction on the axial length after blind spot stimulation. CONCLUSIONS: These findings demonstrate that stimulating melanopsin-expressing axons of ipRGCs at the blind spot with blue light increases choroidal thickness in young adults. This has potential implications for regulating eye growth.

3.
BMJ Open Gastroenterol ; 11(1)2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38519047

ABSTRACT

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a minimally invasive therapeutic option to treat the sequelae of portal hypertension. It is unclear whether current international recommendations are reflected in current clinical practice across Australia and the extent of variations in care. This study aimed to address this gap in knowledge and benchmark the current landscape of TIPS services in Australia against international guidelines. METHODS: We designed a 42-item questionnaire according to practice-based recommendations and standards of international guidelines to investigate current landscape of TIPS service across four key domains: (1) service provision, (2) patient selection and indications, (3) best procedure practice, and (4) postoperative care. RESULTS: Gastroenterologist/hepatologists from 23 major liver centres (67.6%) across Australia currently performing TIPS completed the questionnaire. Between 2017 and 2020, there were 456 elective TIPS insertions. Units offering TIPS service had a low median number of TIPS insertions (n=7 per annum). More than half of respondents (56.5%) did not have institutional clinical practice protocols. There was marked variation in practices across institutions in terms of TIPS indications and patient selection. Despite variations, the success rate of elective TIPS was high at 91.7% (79-100%), with 86.6% (29-100%) for rescue TIPS. There was significant variation in postoperative follow-up and care. CONCLUSION: Current TIPS practice in Australia varies significantly across institutions. There is a need for a national consensus clinical practice guidelines to improve access and minimise unwarranted variation. A national registry for TIPS could measure, monitor, and report on quality of clinical care and patient outcomes.


Subject(s)
Hypertension, Portal , Portasystemic Shunt, Transjugular Intrahepatic , Humans , Portasystemic Shunt, Transjugular Intrahepatic/methods , Hypertension, Portal/surgery , Hypertension, Portal/complications , Liver Cirrhosis/complications , Australia/epidemiology
4.
Gut Microbes ; 16(1): 2331520, 2024.
Article in English | MEDLINE | ID: mdl-38517357

ABSTRACT

Bacteriophages (phages) are estimated to be the most abundant microorganisms on Earth. Their presence in human blood suggests that they can translocate from non-sterile sites such as the gastrointestinal tract where they are concentrated. To examine phage translocation ex vivo, we adapted a primary colonoid monolayer model possessing cell diversity and architecture, and a thick layer of mucus akin to the colonic environment in vivo. We show that the colonoid monolayer is superior to the Caco-2 cell-line model, possessing intact and organized tight junctions and generating a physiologically relevant mucus layer. We showed, using two different phages, that translocation across the colonoid monolayer was largely absent in differentiated monolayers that express mucus, unlike Caco-2 cultures that expressed little to no mucus. By stimulating mucus production or removing mucus, we further demonstrated the importance of colonic mucus in preventing phage translocation. Finally, we used etiological drivers of gut permeability (alcohol, fat, and inflammatory cytokines) to measure their effects on phage translocation, demonstrating that all three stimuli have the capacity to amplify phage translocation. These findings suggest that phage translocation does occur in vivo but may be largely dependent on colonic mucus, an important insight to consider in future phage applications.


Subject(s)
Bacteriophages , Gastrointestinal Microbiome , Humans , Caco-2 Cells , Bacteriophages/physiology , Tight Junctions , Colon
5.
J Glaucoma ; 33(2): 101-109, 2024 02 01.
Article in English | MEDLINE | ID: mdl-37523634

ABSTRACT

PRCIS: This study demonstrated significant differences in optic nerve head characteristics in Aboriginal and Torres Strait Islander children compared with non-Indigenous children, which has implications for glaucoma risk and diagnosis in Aboriginal and Torres Strait Islander populations. PURPOSE: The purpose of this study was to examine the optic nerve head (ONH) characteristics of visually normal Aboriginal and Torres Strait Islander children and non-Indigenous Australian children. MATERIALS AND METHODS: Spectral domain optical coherence tomography imaging was performed on the right eye of 95 Aboriginal and Torres Strait Islander children and 149 non-Indigenous Australian children (5-18 years). Horizontal and vertical line scans, centered on the ONH, were analyzed to determine the dimensions of the ONH (Bruch membrane opening diameter), optic cup diameter, Bruch membrane opening minimum rim width, and the peripapillary retinal nerve fiber layer thickness. RESULTS: The vertical but not horizontal Bruch membrane opening diameter of Aboriginal and Torres Strait Islander children was significantly larger than non-Indigenous children (mean difference: 0.09 mm, P = 0.001). The horizontal (mean difference: 0.12 mm, P = 0.003) and vertical cup diameter (mean difference: 0.16 mm, P < 0.001) were also significantly larger in Aboriginal and Torres Strait Islander children, as were the horizontal and vertical cup-to-disc ratios (both P < 0.01). Aboriginal and Torres Strait Islander children also had a significantly thinner Bruch membrane opening minimum rim width in the superior, nasal, and temporal meridians (all P < 0.001). Peripapillary retinal nerve fiber layer thickness did not differ between groups. CONCLUSIONS: Differences exist in the ONH structure between Aboriginal and Torres Strait Islander children and non-Indigenous children, which may have implications for the detection and monitoring of ocular disease in this population and highlights the need to extend this research to the adult population.


Subject(s)
Australian Aboriginal and Torres Strait Islander Peoples , Optic Disk , Child , Humans , Australia/epidemiology , Intraocular Pressure , Tomography, Optical Coherence
6.
Ophthalmic Physiol Opt ; 44(1): 42-51, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37787443

ABSTRACT

INTRODUCTION: Hyperopia is associated with reduced vision and educational outcomes in schoolchildren. This study explored the impact of clinically significant hyperopia (≥+2.00 D) on visual function in schoolchildren and compared the ability of different screening tests (alone and in combination) to detect this level of hyperopia. METHODS: Vision testing including monocular logMAR visual acuity (VA) measured to threshold (distance [DVA], near [NVA] and DVA through a plus lens [+2.50 D]), stereoacuity and cycloplegic autorefraction (tropicamide 1%) were undertaken on 263 schoolchildren (mean age: 11.76 years ± 3.38) in Queensland, Australia. Vision measures were compared between children with clinically significant hyperopia in at least one meridian (≥+2.00 D) and emmetropia/low hyperopia (>0.00 and <+2.00 D). Receiver operating curve (ROC) analysis was performed to identify optimal pass/fail criteria for each test and the diagnostic accuracy of individual and combinations of tests. RESULTS: Thirty-two children had clinically significant hyperopia and 225 had emmetropia/low hyperopia. DVA and NVA were worse (p < 0.01), while the difference in DVA through a plus lens was less in children with clinically significant hyperopia (p < 0.01). ROC analysis for individual tests resulted in areas under the curve (AUCs) ranging from 0.65 to 0.85. Combining screening tests revealed that failing one or more of the following tests was most effective for detecting hyperopia: DVA, NVA and difference in DVA through a plus lens, resulting in a sensitivity and specificity of 72% and 81%, respectively. CONCLUSION: Significant differences in visual function existed between schoolchildren with clinically significant hyperopia and emmetropia/low hyperopia. Combining measures of DVA and NVA and the difference in DVA through a plus lens demonstrated good discriminative ability for detecting clinically significant hyperopia in this population.


Subject(s)
Hyperopia , Vision Screening , Child , Humans , Hyperopia/diagnosis , Visual Acuity , Vision Tests , Emmetropia , Sensitivity and Specificity , Vision Screening/methods
7.
Transl Vis Sci Technol ; 12(11): 18, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37962538

ABSTRACT

Purpose: To objectively quantify near-work gaze behaviors and the visual environment during reading tasks performed on a smartphone and on paper in both indoor and outdoor environments in myopes and emmetropes. Methods: A novel wearable gaze and viewing distance tracking device was used to quantify near-work gaze behaviors (focusing demand) and the visual environment (20° peripheral scene relative defocus) during a series of reading tasks. Data from nine myopes (mean age, 21 ± 1.4 years) and 10 emmetropes (21 ± 0.8 years) were analyzed. Five-minute reading tasks (matched for font type and size) were performed under four conditions: reading from a smartphone indoors, paper indoors, smartphone outdoors, and paper outdoors. Results: A significantly greater focusing demand (closer viewing distance) was found with smartphone-based reading (mean, 3.15 ± 0.74 D) compared to paper-based reading (2.67 ± 0.48 D) (P < 0.001), with the differences being greatest for myopic participants (P = 0.04). Smartphone reading was also associated with greater peripheral scene relative myopic defocus (P < 0.001). Although near-work behaviors were similar between environments, significantly more relative myopic defocus was found at the start of the paper-based task when performed outdoors compared to indoors (P = 0.02). Conclusions: Significant differences in focusing demand and scene relative defocus within a 20° field were found to be associated with reading tasks performed on a smartphone and paper in indoor and outdoor environments. Translational Relevance: These findings highlight the complex interaction between near-work behaviors and the visual environment and demonstrate that factors of potential importance to myopia development vary between paper-based and smartphone-based near tasks.


Subject(s)
Fixation, Ocular , Myopia , Humans , Young Adult , Myopia/diagnosis , Myopia/epidemiology , Environment , Reading
8.
Clin Exp Optom ; : 1-8, 2023 Oct 17.
Article in English | MEDLINE | ID: mdl-37848182

ABSTRACT

CLINICAL RELEVANCE: Optical coherence tomography angiography (OCT-A) indices are likely to change across time and optometrists should be aware of the variability expected during childhood development and in healthy adults. BACKGROUND: Cross-sectional studies have shown that OCT-A indices are associated with age in adults and children. The aim of this study is to investigate longitudinal changes in retinal and choroidal OCT-A indices over 1 year among healthy children and young adults. METHODS: This prospective longitudinal study captured macular OCT-A and OCT scans, and biometry measures at baseline and 1-year follow-up for 22 adults (18-30 years; -6.87 to +0.37 D) and 21 children (6-15 years; -5.75 to +0.25 D). Superficial and deep retinal layer, choriocapillaris and deep choroidal en face OCT-A images were analysed to extract magnification-corrected vascular indices in foveal, parafoveal and perifoveal regions. The retinal indices included foveal avascular zone metrics, perfusion, and vessel density. Flow deficit number, size, and density were extracted from choriocapillaris and perfusion density from deep choroid. Associations between annual changes in the OCT-A indices and axial length and baseline refraction were also studied. RESULTS: Among children, significant reductions were noted only in parafoveal superficial retinal and foveal and perifoveal deep retinal layer indices over 1 year (p < 0.05). Choroidal OCT-A indices in children and both retinal and choroidal OCT-A indices in adults did not show significant changes. Myopia was associated with a larger reduction in the perifoveal retinal OCT-A indices in children, and with increases in sub-foveal and sub-parafoveal choroidal indices in adults. There were associations between OCT-A indices and axial length changes but differently in adults and children. CONCLUSIONS: Significant changes were noted in retinal OCT-A indices over 1 year among children but not adults. In comparison, choroidal OCT-A indices in adults and children showed a stable morphology over this period of time.

9.
BMC Gastroenterol ; 23(1): 356, 2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37845625

ABSTRACT

OBJECTIVE: Delivering effective secondary preventive and integrated care has the potential to break the revolving-door phenomenon of frequent readmissions in patients with advanced chronic liver disease. To address this, we launched the Care Coordination of Liver Disease (CCoLD) pilot, a novel nurse-led cirrhosis clinic in Western Sydney. METHODS AND ANALYSIS: Following an index presentation to Blacktown or Mount Druitt hospitals (BMDH), patients (n = 89, matched by age, sex, and MELD-NA) were consecutively either followed up by the CCoLD clinical nurse consultant (intervention cohort) or received standard care (control cohort). Controlled evaluation of the impact of the nurse-led clinic was carried out for a 3-month period including readmission rates, survival, and cost effectiveness. RESULTS: The inaugural nurse-led clinic led to improvement in patient-level outcomes including a reduction in unplanned liver-related readmissions (2.08% for intervention cohort vs 12.2% for control cohort, p < 0.01), and mortality at 30 days (0% for intervention cohort vs 7.3% for control cohort, p = 0.03). Similar trends were observed at 90 days from index discharge. No deaths were observed in the intervention cohort as compared to the control cohort at 90 days (0% versus 7.3%, p = 0.03), while unplanned liver-related readmissions were 10.41% for the intervention cohort vs 19.5% for the control cohort (p = 0.115). Moreover, time to readmission was significantly longer in the intervention cohort, resulting in an overall cost-effective intervention. CONCLUSION: These findings highlight the significant impact of optimised care-coordination. A nurse-led clinic can deliver patient-centred, goal-directed, and cost-effective secondary prevention and care. A multicentre randomised trial for wider evaluation of these findings is warranted.


Subject(s)
Nurse's Role , Patient Readmission , Humans , Liver Cirrhosis/therapy , Patient Discharge , Male , Female
10.
JHEP Rep ; 5(10): 100837, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37691688

ABSTRACT

Background and Aims: Although type 2 innate lymphoid cells (ILC2s) were originally found to be liver-resident lymphocytes, the role and importance of ILC2 in liver injury remains poorly understood. In the current study, we sought to determine whether ILC2 is an important regulator of hepatic ischaemia/reperfusion injury (IRI). Methods: ILC2-deficient mice (ICOS-T or NSG) and genetically modified ILC2s were used to investigate the role of ILC2s in murine hepatic IRI. Interactions between ILC2s and eosinophils or macrophages were studied in coculture. The role of human ILC2s was assessed in an immunocompromised mouse model of hepatic IRI. Results: Administration of IL-33 prevented hepatic IRI in association with reduction of neutrophil infiltration and inflammatory mediators in the liver. IL-33-treated mice had elevated numbers of ILC2s, eosinophils, and regulatory T cells. Eosinophils, but not regulatory T cells, were required for IL-33-mediated hepatoprotection in IRI mice. Depletion of ILC2s substantially abolished the protective effect of IL-33 in hepatic IRI, indicating that ILC2s play critical roles in IL-33-mediated liver protection. Adoptive transfer of ex vivo-expanded ILC2s improved liver function and attenuated histologic damage in mice subjected to IRI. Mechanistic studies combining genetic and adoptive transfer approaches identified a protective role of ILC2s through promoting IL-13-dependent induction of anti-inflammatory macrophages and IL-5-dependent elevation of eosinophils in IRI. Furthermore, in vivo expansion of human ILC2s by IL-33 or transfer of ex vivo-expanded human ILC2s ameliorated hepatic IRI in an immunocompromised mouse model of hepatic IRI. Conclusions: This study provides insight into the mechanisms of ILC2-mediated liver protection that could serve as therapeutic targets to treat acute liver injury. Impact and Implications: We report that type 2 innate lymphoid cells (ILC2s) are important regulators in a mouse model of liver ischaemia/reperfusion injury (IRI). Through manipulation of macrophage and eosinophil phenotypes, ILC2s mitigate liver inflammation and injury during liver IRI. We propose that ILC2s have the potential to serve as a therapeutic tool for protecting against acute liver injury and lay the foundation for translation of ILC2 therapy to human liver disease.

11.
Invest Ophthalmol Vis Sci ; 64(6): 4, 2023 05 01.
Article in English | MEDLINE | ID: mdl-37126359

ABSTRACT

The choroid is the richly vascular layer of the eye located between the sclera and Bruch's membrane. Early studies in animals, as well as more recent studies in humans, have demonstrated that the choroid is a dynamic, multifunctional structure, with its thickness directly and indirectly subject to modulation by a variety of physiologic and visual stimuli. In this review, the anatomy and function of the choroid are summarized and links between the choroid, eye growth regulation, and myopia, as demonstrated in animal models, discussed. Methods for quantifying choroidal thickness in the human eye and associated challenges are described, the literature examining choroidal changes in response to various visual stimuli and refractive error-related differences are summarized, and the potential implications of the latter for myopia are considered. This review also allowed for the reexamination of the hypothesis that short-term changes in choroidal thickness induced by pharmacologic, optical, or environmental stimuli are predictive of future long-term changes in axial elongation, and the speculation that short-term choroidal thickening can be used as a biomarker of treatment efficacy for myopia control therapies, with the general conclusion that current evidence is not sufficient.


Subject(s)
Axial Length, Eye , Myopia , Animals , Humans , Choroid/physiology , Bruch Membrane , Models, Animal , Tomography, Optical Coherence/methods
12.
Int J Mol Sci ; 24(10)2023 May 15.
Article in English | MEDLINE | ID: mdl-37240132

ABSTRACT

The hepatitis C virus (HCV) relies on cellular lipid pathways for virus replication and also induces liver steatosis, but the mechanisms involved are not clear. We performed a quantitative lipidomics analysis of virus-infected cells by combining high-performance thin-layer chromatography (HPTLC) and mass spectrometry, using an established HCV cell culture model and subcellular fractionation. Neutral lipid and phospholipids were increased in the HCV-infected cells; in the endoplasmic reticulum there was an ~four-fold increase in free cholesterol and an ~three-fold increase in phosphatidyl choline (p < 0.05). The increase in phosphatidyl choline was due to the induction of a non-canonical synthesis pathway involving phosphatidyl ethanolamine transferase (PEMT). An HCV infection induced expression of PEMT while knocking down PEMT with siRNA inhibited virus replication. As well as supporting virus replication, PEMT mediates steatosis. Consistently, HCV induced the expression of the pro-lipogenic genes SREBP 1c and DGAT1 while inhibiting the expression of MTP, promoting lipid accumulation. Knocking down PEMT reversed these changes and reduced the lipid content in virus-infected cells. Interestingly, PEMT expression was over 50% higher in liver biopsies from people infected with the HCV genotype 3 than 1, and three times higher than in people with chronic hepatitis B, suggesting that this may account for genotype-dependent differences in the prevalence of hepatic steatosis. PEMT is a key enzyme for promoting the accumulation of lipids in HCV-infected cells and supports virus replication. The induction of PEMT may account for virus genotype specific differences in hepatic steatosis.


Subject(s)
Fatty Liver , Hepatitis C, Chronic , Hepatitis C , Humans , Hepacivirus/genetics , Hepacivirus/metabolism , Transferases/metabolism , Hepatitis C/genetics , Fatty Liver/pathology , Virus Replication , Genotype , Cholesterol/metabolism , Phosphatidylcholines/metabolism , Phenotype , Phosphatidylethanolamine N-Methyltransferase/genetics
13.
J Cardiovasc Nurs ; 38(5): 492-510, 2023.
Article in English | MEDLINE | ID: mdl-37249544

ABSTRACT

BACKGROUND: Comorbid depression and/or anxiety symptoms occur in 25% of patients attending cardiac rehabilitation (CR) programs and are associated with poorer prognosis. There is a need to evaluate psychological interventions, including meditation, that have potential to improve psychological health in CR programs. AIMS: The aim of this study was to determine the feasibility and acceptability of integrating a meditation intervention into an existing Australian CR program for the reduction of depression and anxiety symptoms. METHODS: This was a mixed-methods feasibility randomized controlled trial. Thirty-one patients with CVD and, at a minimum, mild depression and/or anxiety symptoms were randomized to meditation and standard CR or to standard CR alone. A 16-minute guided group meditation was delivered face-to-face once a week for 6 weeks, with daily self-guided meditation practice between sessions. Feasibility outcomes included screening, recruitment, and retention. Semistructured interviews of patients' (n = 10) and health professionals' (n = 18) perspectives of intervention participation and delivery were undertaken to assess acceptability. Between-group differences in depression, anxiety, stress, self-efficacy for mindfulness, and health status at 6 and 12 weeks were also assessed. RESULTS AND CONCLUSION: Meditation was considered feasible, with 83% (12/15) of the intervention group completing an average of 3.13 (SD, 2.56) out of 6 group meditation sessions and 5.28 (SD, 8.50) self-guided sessions. Meditation was considered acceptable by patients, clinicians, and health managers. Between-group differences in the number of CR sessions completed favored the intervention group in per-protocol analyses (intervention group vs control group, 12 vs 9 sessions; P = .014), which suggests that meditation may be useful to improve patients' adherence to exercise-based CR program.


Subject(s)
Heart Diseases , Meditation , Humans , Meditation/methods , Feasibility Studies , Mentors , Australia
14.
Ophthalmic Physiol Opt ; 43(4): 827-841, 2023 07.
Article in English | MEDLINE | ID: mdl-37140840

ABSTRACT

INTRODUCTION: Despite the known associations between near work and myopia, and retinal image quality and eye growth, accommodation-induced changes in higher order aberrations (HOA's) and retinal image quality in children with different refractive errors are poorly understood. METHODS: Ocular HOA's were measured using a Hartmann-Shack wavefront sensor (COAS-HD, Wavefront Sciences) in 18 myopic and 18 age- and sex-matched non-myopic children during short-term accommodation tasks (four demands of 0, 3, 6 and 9 D) presented using a Badal optometer. Eighth order Zernike polynomials were fitted across a 2.3 mm pupil diameter to determine refractive power vectors (M, J180 and J45 ) and the accommodation error, and a 4 mm pupil was used for HOA analyses. Retinal image quality was examined using the visual Strehl ratio based on the optical transfer function (VSOTF) for third to eighth radial orders only. RESULTS: Most refractive error group differences were observed for the 6 and 9 D demands. Myopic children underwent greater changes in with-the-rule astigmatism (J180 ), higher order and third order RMS values, primary vertical ( C 3 - 1 ) and horizontal coma ( C 3 1 ), and several other individual Zernike coefficients compared with non-myopic children (all refractive error group by demand interaction p-values of ≤0.02). Non-myopic children exhibited a greater negative shift in primary ( C 4 0 ) and positive shift in secondary spherical aberration ( C 6 0 ) (both refractive error group by demand interaction p-values of ≤0.002). The VSOTF degraded for the 6 and 9 D demands in both groups, but the myopic children underwent a greater mean (SE) reduction from 0 D of -0.274 (0.048) for the 9 D demand, compared with -0.131 (0.052) for the non-myopic children (p = 0.001). CONCLUSION: These results may have implications for the association between near work, accommodation and myopia development, particularly related to the use of short working distances during near tasks.


Subject(s)
Myopia , Refractive Errors , Child , Humans , Refraction, Ocular , Refractive Errors/diagnosis , Myopia/diagnosis , Accommodation, Ocular , Retina/diagnostic imaging
15.
Methods Protoc ; 6(2)2023 Mar 28.
Article in English | MEDLINE | ID: mdl-37104017

ABSTRACT

Increasing evidence strongly supports the key role of the tumour microenvironment in response to systemic therapy, particularly immune checkpoint inhibitors (ICIs). The tumour microenvironment is a complex tapestry of immune cells, some of which can suppress T-cell immunity to negatively impact ICI therapy. The immune component of the tumour microenvironment, although poorly understood, has the potential to reveal novel insights that can impact the efficacy and safety of ICI therapy. Successful identification and validation of these factors using cutting-edge spatial and single-cell technologies may enable the development of broad acting adjunct therapies as well as personalised cancer immunotherapies in the near future. In this paper we describe a protocol built upon Visium (10x Genomics) spatial transcriptomics to map and characterise the tumour-infiltrating immune microenvironment in malignant pleural mesothelioma. Using ImSig tumour-specific immune cell gene signatures and BayesSpace Bayesian statistical methodology, we were able to significantly improve immune cell identification and spatial resolution, respectively, improving our ability to analyse immune cell interactions within the tumour microenvironment.

16.
Sci Rep ; 13(1): 3551, 2023 03 02.
Article in English | MEDLINE | ID: mdl-36864086

ABSTRACT

This prospective study investigated the magnitude and pattern of variation in choroidal optical coherence tomography angiography (OCT-A) indices every 4 h over 24 h in healthy young myopic (n = 24) and non-myopic (n = 20) adults. Choriocapillaris and deep choroid en-face images from macular OCT-A scans were analysed from each session to extract magnification-corrected vascular indices including choriocapillaris flow deficit number, size and density and deep choroid perfusion density in the sub-foveal, sub-parafoveal, and sub-perifoveal regions. Choroidal thickness was also obtained from structural OCT scans. Significant variations over 24 h (P < 0.05) were observed in most of the choroidal OCT-A indices excluding sub-perifoveal flow deficit number, with peaks observed between 2 to 6 AM. For myopes, peaks occurred significantly earlier (3-5 h), and the diurnal amplitude was significantly greater for sub-foveal flow deficit density (P = 0.02) and deep choroidal perfusion density (P = 0.03) compared with non-myopes. Choroidal thickness also showed significant diurnal changes (P < 0.05) with peaks between 2 to 4 AM. Significant correlations were found between diurnal amplitudes or acrophases of choroidal OCT-A indices and choroidal thickness, intraocular pressure, and systemic blood pressure. This provides the first comprehensive diurnal assessment of choroidal OCT-A indices over 24 h.


Subject(s)
Myopia , Tomography, Optical Coherence , Young Adult , Humans , Prospective Studies , Angiography , Choroid/diagnostic imaging , Fovea Centralis , Myopia/diagnostic imaging
17.
Biomed Opt Express ; 14(3): 1276-1291, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36950234

ABSTRACT

This study examined anterior corneal, internal ocular, and total ocular higher order aberrations (HOA's), and retinal image quality in a non-myopic, paediatric cohort. Anterior corneal aberrations were derived from corneal topography data captured using a Placido disk videokeratoscope (E300, Medmont International), and whole eye HOA's were measured using a Hartmann-Shack wavefront sensor (COAS-HD, Wavefront Sciences). The associations between HOA's and age, sex, refractive error, and axial length were explored using correlation analyses. Data for 84 children aged between 5 and 12 years (mean ± standard deviation spherical equivalent refraction (SER), +0.63 ± 0.35 D; range 0.00 to +1.75 D) were included, and an eighth order Zernike polynomial was fit for 4 and 6 mm pupil diameters for both the anterior corneal and total ocular HOA's, from which internal ocular HOA's were calculated via subtraction following alignment to a common reference axis (pupil centre). Internal ocular HOA's were of greater magnitude than previous studies of adolescents and adults, however partial internal "compensation" of HOA's was observed, which resulted in reduced levels of HOA's and excellent retinal image quality. Few significant associations were observed between HOA's and age, SER, and axial length (all correlations, p > 0.001), and there were minimal sex-based differences (all comparisons, p > 0.005). Coefficients for vertical coma ( C 3 - 1 and C 5 - 1 ) and spherical aberration ( C 4 0 and C 6 0 ), were most strongly associated with the visual Strehl ratio based on the optical transfer function (VSOTF), which indicated that the absolute magnitudes of these Zernike coefficients have the greatest impact on retinal image quality in this paediatric cohort. These findings provide an improved understanding of the optics and retinal image quality of children's eyes.

18.
Hepatol Int ; 17(3): 542-545, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36971983

ABSTRACT

The perception of high surgical risk among patients with cirrhosis has resulted in a long-standing reluctance to operate. Risk stratification tools, first implemented over 60 years ago, have attempted to assess mortality risk among cirrhotic patients and ensure the best possible outcomes for this difficult to treat cohort. Existing postoperative risk prediction tools including the Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) provide some prediction of risk in counselling patients and their families but tend to overestimate surgical risk. More personalised prediction algorithms such as the Mayo Risk Score and VOCAL-Penn score that incorporate surgery-specific risks have demonstrated a significant improvement in prognostication and can ultimately aid multidisciplinary team determination of potential risks. The development of future risk scores will need to incorporate, first and foremost, predictive efficacy, but perhaps just as important is the feasibility and usability by front-line healthcare professionals to ensure timely and efficient prediction of risk for cirrhotic patients.


Subject(s)
End Stage Liver Disease , Humans , Severity of Illness Index , Liver Cirrhosis/complications , Liver Cirrhosis/surgery , Fibrosis , Risk Factors , Prognosis , Retrospective Studies
20.
Ophthalmic Physiol Opt ; 43(3): 311-318, 2023 05.
Article in English | MEDLINE | ID: mdl-36597948

ABSTRACT

PURPOSE: Eye length increases during accommodation, both on-axis and in the periphery. The aim of this study was to determine whether the peripheral choroid thins with accommodation and to determine the relationship with eye length changes measured at the same location. METHODS: Subjects included 53 young adults in good ocular and general health, with 19 emmetropes and 34 myopes. Measurements from the right eye were made for 0 D and 6 D accommodation stimuli for ±30° horizontal visual field/retinal locations in 10° steps. Valid eye length and choroidal thickness measurements were obtained for 37 and 47 participants, respectively, and both measures were taken for 31 participants. 2.5% phenylephrine was instilled to dilate the pupils. Participants turned their eyes, without head movement, to fixate targets and to make the target 'as clear as possible' during measurements. Correction was made for the influence of lens thickness changing at different peripheral angles. Choroidal thickness was measured with a spectral-domain-Optical Coherence Tomographer. For peripheral images, the internal cross target on the capture screen was moved from the centre to 17.25° nasal/temporal positions. RESULTS: In accordance with previous literature, eye length increased with accommodation. The greatest change (mean ± SD) of 41 ± 17 µm occurred at the centre, with a mean change across the locations of 33 µm. There were no significant differences between emmetropes and myopes. Choroidal thickness decreased with accommodation, with changes being about two-thirds of those occurring for eye length. The greatest change of -30 ± 1 µm occurred at the centre, with a mean change of -21 µm. Greater choroidal thinning occurred for myopes than for emmetropes (23 ± 11 vs. 17 ± 8 µm, p = 0.02). CONCLUSIONS: With accommodation, eye length increased and the choroid thinned, at both central and peripheral positions. Choroidal thinning accounted for approximately 60% of the eye length increase across the horizontal ±30°.


Subject(s)
Axial Length, Eye , Myopia , Young Adult , Humans , Myopia/diagnosis , Accommodation, Ocular , Choroid , Emmetropia , Tomography, Optical Coherence/methods
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