Clinical Approach to Immune-Mediated Hemolytic Anemia and Thrombocytopenia.

Primary immune mediated hemolytic anemia (IMHA) and thrombocytopenia (IMTP) are rare in horses with the conditions more commonly occurring secondary to underlying disease. Several case reports have suggested a link between neoplasia and immune-mediated destruction of platelets and red blood cells. Diagnostic investigations should therefore focus on identifying possible underlying causes such as infections and neoplasia. Immunosuppressive therapy with corticosteroids and azathioprine is the mainstay of treatment but should be used cautiously in cases where underlying infection has not been excluded. Given the frequent association of secondary IMHA and IMTP cases with neoplasia, primary cases generally have a better prognosis.

Risk-Adapted Breast Screening for Women at Low Predicted Risk of Breast Cancer: An Online Discrete Choice Experiment.

BACKGROUND: A risk-stratified breast screening program could offer low-risk women less screening than is currently offered by the National Health Service. The acceptability of this approach may be enhanced if it corresponds to UK women's screening preferences and values. OBJECTIVES: To elicit and quantify preferences for low-risk screening options. METHODS: Women aged 40 to 70 y with no history of breast cancer took part in an online discrete choice experiment. We generated 32 hypothetical low-risk screening programs defined by 5 attributes (start age, end age, screening interval, risk of dying from breast cancer, and risk of overdiagnosis), the levels of which were systematically varied between the programs. Respondents were presented with 8 choice sets and asked to choose between 2 screening alternatives or no screening. Preference data were analyzed using conditional logit regression models. The relative importance of attributes and the mean predicted probability of choosing each program were estimated. RESULTS: Participants (N = 502) preferred all screening programs over no screening. An older starting age of screening, younger end age of screening, longer intervals between screening, and increased risk of dying had a negative impact on support for screening programs (P < 0.01). Although the risk of overdiagnosis was of low relative importance, a decreased risk of this harm had a small positive impact on screening choices. The mean predicted probabilities that risk-adapted screening programs would be supported relative to current guidelines were low (range, 0.18 to 0.52). CONCLUSIONS: A deintensified screening pathway for women at low risk of breast cancer, especially one that recommends a later screening start age, would run counter to women's breast screening preferences. Further research is needed to enhance the acceptability of offering less screening to those at low risk of breast cancer. HIGHLIGHTS: Risk-based breast screening may involve the deintensification of screening for women at low risk of breast cancer.Low-risk screening pathways run counter to women's screening preferences and values.Longer screening intervals may be preferable to a later start age.Work is needed to enhance the acceptability of a low-risk screening pathway.

Protein engineering enables a soakable crystal form of human CDK7 primed for high-throughput crystallography and structure-based drug design.

Cyclin dependent kinase 7 (CDK7) is an important therapeutic kinase best known for its dual role in cell cycle regulation and gene transcription. Here, we describe the application of protein engineering to generate constructs leading to high resolution crystal structures of human CDK7 in both active and inactive conformations. The active state of the kinase was crystallized by incorporation of an additional surface residue mutation (W132R) onto the double phosphomimetic mutant background (S164D and T170E) that yielded the inactive kinase structure. A novel back-soaking approach was developed to determine crystal structures of several clinical and pre-clinical inhibitors of this kinase, demonstrating the potential utility of the crystal system for structure-based drug design (SBDD). The crystal structures help to rationalize the mode of inhibition and the ligand selectivity profiles versus key anti-targets. The protein engineering approach described here illustrates a generally applicable strategy for structural enablement of challenging molecular targets.

Association between emergency department attendances, sociodemographic factors and long-term health conditions in the population of Norfolk and Waveney, England: Cross sectional study.

INTRODUCTION: Demand for urgent and emergency health care in England has grown over the last decade, for reasons that are not clear. Changes in population demographics may be a cause. This study investigated associations between individuals' characteristics (including socioeconomic deprivation and long term health conditions (LTC)) and the frequency of emergency department (ED) attendances, in the Norfolk and Waveney subregion of the East of England. METHODS: The study population was people who were registered with 91 of 106 Norfolk and Waveney general practices during one year from 1 April 2022 to 31 March 2023. Linked primary and secondary care and geographical data included each individual's sociodemographic characteristics, and number of ED attendances during the same year and, for some individuals, LTCs and number of general practice (GP) appointments. Associations between these factors and ED attendances were estimated using Poisson regression models. RESULTS: 1,027,422 individuals were included of whom 57.4% had GP data on the presence or absence of LTC, and 43.1% had both LTC and general practitioner appointment data. In the total population ED attendances were more frequent in individuals aged under five years, (adjusted Incidence Rate Ratio (IRR) 1.25, 95% confidence interval 1.23 to 1.28) compared to 15-35 years); living in more socioeconomically deprived areas (IRR 0.61 (0.60 to 0.63)) for least deprived compared to most deprived,and living closer to the nearest ED. Among individuals with LTC data, each additional LTC was also associated with increased ED attendances (IRR 1.16 (1.15 to 1.16)). Among individuals with LTC and GP appointment data, each additional GP appointment was also associated with increased ED attendances (IRR 1.03 (1.026 to 1.027)). CONCLUSIONS: In the Norfolk and Waveney population, ED attendance rates were higher for young children and individuals living in more deprived areas and closer to EDs. In individuals with LTC and GP appointment data, both factors were also associated with higher ED attendance.

Phase contrast micro-CT with adjustable in-slice spatial resolution at constant magnification.

Objective.To report on a micro computed tomography (micro-CT) system capable of x-ray phase contrast imaging and of increasing spatial resolution at constant magnification.Approach.The micro-CT system implements the edge illumination (EI) method, which relies on two absorbing masks with periodically spaced transmitting apertures in the beam path; these split the beam into an array of beamlets and provide sensitivity to the beamlets' directionality, i.e. refraction. In EI, spatial resolution depends on the width of the beamlets rather than on the source/detector point spread function (PSF), meaning that resolution can be increased by decreasing the mask apertures, without changing the source/detector PSF or the magnification.Main results.We have designed a dedicated mask featuring multiple bands with differently sized apertures and used this to demonstrate that resolution is a tuneable parameter in our system, by showing that increasingly small apertures deliver increasingly detailed images. Phase contrast images of a bar pattern-based resolution phantom and a biological sample (a mouse embryo) were obtained at multiple resolutions.Significance.The new micro-CT system could find application in areas where phase contrast is already known to provide superior image quality, while the added tuneable resolution functionality could enable more sophisticated analyses in these applications, e.g. by scanning samples at multiple scales.

Hospitality Work as Social Reproduction: Embodied and Emotional Labour during COVID-19.

This article focuses on how the imaginary of a 'safe' environment was visualised and conveyed within the hospitality sector during the COVID-19 pandemic, drawing on diaries and interviews with 21 workers in the UK. Our findings show increased workloads for hospitality staff, compounded by anxieties of risk and individualised COVID-19 regulation work. This includes workers' negotiations of corporeal boundaries and distancing from customers, the visible cleaning of communal areas and recuperation and care work for their own bodies and others in shared living spaces. We draw on conceptualisations of embodied and emotional labour to understand these experiences, reflecting on the importance of the actions performed by workers in maintaining community spaces and creating customer confidence in safely enjoying a 'hospitable' environment. This article contributes to social science scholarship of embodied and emotional labour, hospitality and social reproduction.

Diversity of Microbial Mats in the Makgadikgadi Salt Pans, Botswana.

The Makgadikgadi Salt Pans are the remnants of a mega paleo-lake system in the central Kalahari, Botswana. Today, the Makgadikgadi Basin is an arid to semi-arid area receiving water of meteoric origin during the short, wet season. Large microbial mats, which support primary production, are formed due to desiccation during the dry season. This study aimed to characterise the microbial diversity of the microbial mats and the underlying sediment. The focus was the Ntwetwe Pan, located west of the Makgadikgadi Basin. Metagenomic analyses demonstrated that the mats consisted of a high relative abundance of Cyanobacteriota (synonym Cyanobacteria) (20.50-41.47%), Pseudomonadota (synonym Proteobacteria) (15.71 to 32.18%), and Actinomycetota (synonym Actinobacteria) (8.53-32.56%). In the underlying sediments, Pseudomonadota, Actinomycetota, and Euryarchaeota represented over 70% of the community. Localised fluctuations in water content and pH did not significantly affect the microbial diversity of the sediment or the mats.

Perinatal mental health in medical school curricula: a national scoping survey of British universities and student psychiatry societies.

AIMS AND METHOD: With increasing recognition of the prevalence and impact of perinatal mental health (PMH) disorders comes a responsibility to ensure that tomorrow's doctors can support families during the perinatal period. Online surveys seeking information about the inclusion of PMH education in undergraduate curricula were sent to psychiatry curriculum leads and student psychiatry societies from each university medical school in the UK between April and September 2021. RESULTS: Responses were received from 32/35 (91.4%) medical schools. Two-thirds reported specific inclusion of PMH content in the core curriculum, typically integrated into general adult psychiatry or obstetric teaching. Students at the remaining schools were all likely to be examined on the topic or see perinatal cases during at least one clinical attachment. CLINICAL IMPLICATIONS: PMH education offers an opportunity for collaboration between psychiatry and other disciplines. Future work looking at educational case examples with objective outcomes would be valuable.

Understanding barriers and enablers to participation in a proposed online lifestyle intervention for older adults with age-related macular degeneration to guide programme implementation.

Age-related macular degeneration (AMD) is a blinding condition associated with depression, loneliness and unhealthy lifestyle behaviours which drives AMD progression. We have proposed the first online lifestyle intervention for AMD, called Movement, Interaction and Nutrition for Greater Lifestyles in the Elderly (MINGLE) to promote positive lifestyle changes and reduce loneliness. This qualitative grounded-theory study explored enablers and barriers to future participation in MINGLE for older adults with AMD. Thirty-one participants were interviewed and thematic analysis revealed nine themes. Enablers to participation were: socialising and learning about AMD, motivation to improve health, programme accessibility and structure. Barriers were: lack of time, technology, limited knowledge regarding holistic interventions, vision-related issues, mobility and negative perception of group interactions. These factors must be considered when developing lifestyle interventions for AMD patients to maximise participation. Supporting technology use and raising awareness about benefits of healthy lifestyle behaviours for AMD may help overcome these barriers.

Enabling synthesis in fragment-based drug discovery (FBDD): microscale high-throughput optimisation of the medicinal chemist's toolbox reactions.

Miniaturised high-throughput experimentation (HTE) is widely employed in industrial and academic laboratories for rapid reaction optimisation using material-limited, multifactorial reaction condition screening. In fragment-based drug discovery (FBDD), common toolbox reactions such as the Suzuki-Miyaura and Buchwald-Hartwig cross couplings can be hampered by the fragment's intrinsic heteroatom-rich pharmacophore which is required for ligand-protein binding. At Astex, we are using microscale HTE to speed up reaction optimisation and prevent target down-prioritisation. By identifying catalyst/base/solvent combinations which tolerate unprotected heteroatoms we can rapidly optimise key cross-couplings and expedite route design by avoiding superfluous protecting group manipulations. However, HTE requires extensive upfront training, and this modern automated synthesis technique largely differs to the way organic chemists are traditionally trained. To make HTE accessible to all our synthetic chemists we have developed a semi-automated workflow enabled by pre-made 96-well screening kits, rapid analytical methods and in-house software development, which is empowering chemists at Astex to run HTE screens independently with minimal training.

Mechanisms of Resistance to Immunotherapy in Hepatocellular Carcinoma.

Systemic treatment for advanced hepatocellular carcinoma (HCC) has been revolutionized over the last few years following the approval of immune checkpoint inhibitors (ICI). Despite the promising survival extension seen with ICI combination regimens, responses are not universally seen and the optimal partner for programmed cell death 1 pathway inhibitors remains to be identified. Even fewer encouraging results have been demonstrated with ICI used for monotherapy. Several mechanisms of resistance have been described so far, involving characteristics of cancer cells (intrinsic mechanisms) and of the surrounding tumor microenvironment (extrinsic mechanisms). Factors related to therapy may also contribute to the development of resistance. Increasing research efforts are being dedicated to the discovery of novel approaches and targets to overcome resistance, some of which may be introduced into clinic in the future. Herein we describe a selection of resistance mechanisms that have been involved in impairing response to ICI and propose potential therapeutic approaches to overcome resistance.

Voltage-gated sodium channels, sodium transport and progression of solid tumours.

Sodium (Na+) concentration in solid tumours of different origin is highly dysregulated, and this corresponds to the aberrant expression of Na+ transporters. In particular, the α subunits of voltage gated Na+ channels (VGSCs) raise intracellular Na+ concentration ([Na+]i) in malignant cells, which influences the progression of solid tumours, predominantly driving cancer cells towards a more aggressive and metastatic phenotype. Conversely, re-expression of VGSC ß subunits in cancer cells can either enhance tumour progression or promote anti-tumourigenic properties. Metastasis is the leading cause of cancer-related mortality, highlighting an important area of research which urgently requires improved therapeutic interventions. Here, we review the extent to which VGSC subunits are dysregulated in solid tumours, and consider the implications of such dysregulation on solid tumour progression. We discuss current understanding of VGSC-dependent mechanisms underlying increased invasive and metastatic potential of solid tumours, and how the complex relationship between the tumour microenvironment (TME) and VGSC expression may further drive tumour progression, in part due to the interplay of infiltrating immune cells, cancer-associated fibroblasts (CAFs) and insufficient supply of oxygen (hypoxia). Finally, we explore past and present clinical trials that investigate utilising existing VGSC modulators as potential pharmacological options to support adjuvant chemotherapies to prevent cancer recurrence. Such research demonstrates an exciting opportunity to repurpose therapeutics in order to improve the disease-free survival of patients with aggressive solid tumours.

The molecular basis of drug selectivity for α5 subunit-containing GABAA receptors.

α5 subunit-containing γ-aminobutyric acid type A (GABAA) receptors represent a promising drug target for neurological and neuropsychiatric disorders. Altered expression and function contributes to neurodevelopmental disorders such as Dup15q and Angelman syndromes, developmental epilepsy and autism. Effective drug action without side effects is dependent on both α5-subtype selectivity and the strength of the positive or negative allosteric modulation (PAM or NAM). Here we solve structures of drugs bound to the α5 subunit. These define the molecular basis of binding and α5 selectivity of the ß-carboline, methyl 6,7-dimethoxy-4-ethyl-ß-carboline-3-carboxylate (DMCM), type II benzodiazepine NAMs, and a series of isoxazole NAMs and PAMs. For the isoxazole series, each molecule appears as an 'upper' and 'lower' moiety in the pocket. Structural data and radioligand binding data reveal a positional displacement of the upper moiety containing the isoxazole between the NAMs and PAMs. Using a hybrid molecule we directly measure the functional contribution of the upper moiety to NAM versus PAM activity. Overall, these structures provide a framework by which to understand distinct modulator binding modes and their basis of α5-subtype selectivity, appreciate structure-activity relationships, and empower future structure-based drug design campaigns.

Technical note: Cartilage imaging with sub-cellular resolution using a laboratory-based phase-contrast x-ray microscope.

BACKGROUND: Microscopic imaging of cartilage is a key tool for the study and development of treatments for osteoarthritis. When cellular and sub-cellular resolution is required, histology remains the gold standard approach, albeit limited by the lack of volumetric information as well as by processing artifacts. Cartilage imaging with the sub-cellular resolution has only been demonstrated in the synchrotron environment. PURPOSE: To provide a proof-of-concept demonstration of the capability of a laboratory-based x-ray phase-contrast microscope to resolve sub-cellular features in a cartilage sample. METHODS: This work is based on a laboratory-based x-ray microscope using intensity-modulation masks. The structured nature of the beam, resulting from the mask apertures, allows the retrieval of three contrast channels, namely, transmission, refraction and dark-field, with resolution depending only on the mask aperture width. An ex vivo equine cartilage sample was imaged with the x-ray microscope and results were validated with synchrotron tomography and histology. RESULTS: Individual chondrocytes, that is, cells responsible for cartilage formation, could be detected with the laboratory-based microscope. The complementarity of the three retrieved contrast channels allowed the detection of sub-cellular features in the chondrocytes. CONCLUSIONS: We provide the first proof-of-concept of imaging cartilage tissue with sub-cellular resolution using a laboratory-based x-ray microscope.

Associations Between Cardiovascular Risk Factors and Audiometric Hearing: Findings From the Canadian Longitudinal Study on Aging.

OBJECTIVES: The objectives of the study were to determine, among a population-based sample of Canadian adults, if risk factors for cardiovascular disease (alone and in combination) were associated with hearing loss. Cross-sectional and longitudinal associations (the latter with about 3 years of follow-up) were examined. Risk factors considered included diabetes, dyslipidemia, hypertension, obesity, and smoking. We also aimed to determine if associations were modified by sex and age group (45 to 54, 55 to 64, 65 to 74, and 75 to 86 years old at baseline). DESIGN: A secondary analysis of data collected for the Canadian Longitudinal Study on Aging was performed. Data were collected in two waves, the first between 2012 and 2015, and the second between 2015 and 2018. Hearing was measured using screening air-conduction pure-tone audiometry. The outcome of interest was defined as the mid-frequency (1000, 2000, 3000, and 4000 Hz) pure-tone average for both ears. Diabetes was defined based on self-reported physician diagnosis, use of diabetes medications, or a hemoglobin A1c level ≥6.5%. Dyslipidemia was determined by blood lipid profile as defined using the Canadian guidelines for the diagnosis and treatment of dyslipidemia (low-density lipoprotein cholesterol ≥3.5 mmol/L or non-high-density lipoprotein cholesterol ≥4.3 mmol/L). Hypertension was determined by self-reported physician diagnosis or an average systolic blood pressure ≥140 mm Hg or an average diastolic blood pressure ≥90 mm Hg. Obesity was defined as a waist-to-height ratio ≥0.6. Smoking history was determined by self-report (current/former/never-smoker). Two composite measures of cardiovascular risk were also constructed: a count of the number of risk factors and a general cardiovascular risk profile (Framingham) score. Independent associations between risk factors for cardiovascular disease and hearing were determined using multivariable regression models. Survey weights were incorporated into the analyses. All results were disaggregated by sex. Effect modification according to age was determined using multiplicative interaction terms between the age group and each of the risk factor variables. A complete case (listwise deletion) approach was performed for the primary analysis. We then repeated the multivariable regression analyses using multiple imputation using chained equations to determine if the different approaches to dealing with missing data qualitatively changed the outcomes. RESULTS: In longitudinal analyses, hypertension and the general cardiovascular risk profile score were associated with greater loss of hearing over the 3-year follow-up period for both sexes. In addition, smoking in males and obesity in females were associated with faster rates of hearing decline. In cross-sectional analyses, smoking, obesity, diabetes, and composite measures were each independently associated with worse hearing for both sexes (although for females, obesity was only associated with hearing loss in the 55 to 64-year-old age group). The results were similar for the complete case and multiple imputation approaches, but more cross-sectional associations were observed using multiple imputation. CONCLUSIONS: Diabetes, obesity, hypertension, and smoking were associated with hearing loss. Higher combinations of risk factors increased the risk of hearing loss. Further studies are needed to confirm age and sex differences and whether interventions to address these risk factors could slow the progression of hearing loss in older adults.

Hyalocytes in proliferative vitreo-retinal diseases.

Introduction: Hyalocytes are sentinel macrophages residing within the posterior vitreous cortex anterior to the retinal inner limiting membrane (ILM). Following anomalous PVD and vitreoschisis, hyalocytes contribute to paucicellular (vitreo-macular traction syndrome, macular holes) and hypercellular (macular pucker, proliferative vitreo-retinopathy, proliferative diabetic vitreo-retinopathy) diseases. Areas covered: Studies of human tissues employing dark-field, phase, and electron microscopy; immunohistochemistry; and in vivo imaging of human hyalocytes. Expert opinion: Hyalocytes are important in early pathophysiology, stimulating cell migration and proliferation, as well as subsequent membrane contraction and vitreo-retinal traction. Targeting hyalocytes early could mitigate advanced disease. Ultimately, eliminating the role of vitreous and hyalocytes may prevent proliferative vitreo-retinal diseases entirely.

Community stakeholder-driven technology solutions towards rural health equity: A concept mapping study in Western Canada.

BACKGROUND: Technology holds great potential for promoting health equity for rural populations, who have more chronic illnesses than their urban counterparts but less access to services. Yet, more participatory research approaches are needed to gather community-driven health technology solutions. The purpose was to collaboratively identify and prioritize action strategies for using technology to promote rural health equity through community stakeholder engagement. METHODS: Concept mapping, a quantitative statistical technique, embedded within a qualitative approach, was used to identify and integrate technological solutions towards rural health equity from community stakeholders in three steps: (1) idea generation; (2) sorting and rating feasibility/importance and (3) group interpretation. Purposeful recruitment strategies were used to recruit key stakeholders and organizational representatives from targeted rural communities. RESULTS: Overall, 34 rural community stakeholders from western Canada (76% female, mean age = 55.4 years) participated in the concept mapping process. In Step 1, 84 ideas were generated that were reduced to a pool of 30. Multidimensional scaling and cluster analysis resulted in a six-cluster map representing how technological solutions can contribute toward rural health equity. The clusters of ideas included technological solutions and applications, but also ideas to make health care more accessible regardless of location, training and support in the use of technology, ensuring digital tools are simplified for ease of use, technologies to support collaboration among healthcare professionals and ideas for overcoming challenges to data sharing across health systems/networks. Each cluster included ideas that were rated as equally important and feasible. Key themes included organizational and individual-level solutions and connecting patients to newly developed technologies. CONCLUSIONS: Overall, the grouping of solutions revealed that technological applications require not only access but also support and collaboration. Concept mapping is a tool that can engage rural community stakeholders in the identification of technological solutions for promoting rural health equity. PATIENT OR PUBLIC CONTRIBUTION: Rural community stakeholders were involved in the generation and interpretation of technological solutions towards rural health equity in a three-step process: (1) individual brainstorming of ideas, (2) sorting and rating all ideas generated and (3) collective interpretation and group consensus on final results.

Fragment-Based Discovery of a Novel, Brain Penetrant, Orally Active HDAC2 Inhibitor.

Fragment-based ligand discovery was successfully applied to histone deacetylase HDAC2. In addition to the anticipated hydroxamic acid- and benzamide-based fragment screening hits, a low affinity (∼1 mM) α-amino-amide zinc binding fragment was identified, as well as fragments binding to other regions of the catalytic site. This alternative zinc-binding fragment was further optimized, guided by the structural information from protein-ligand complex X-ray structures, into a sub-µM, brain penetrant, HDAC2 inhibitor (17) capable of modulating histone acetylation levels in vivo.

QM/MM Simulations Reveal the Determinants of Carbapenemase Activity in Class A ß-Lactamases.

ß-lactam antibiotic resistance in Gram-negative bacteria, primarily caused by ß-lactamase enzymes that hydrolyze the ß-lactam ring, has become a serious clinical problem. Carbapenems were formerly considered "last resort" antibiotics because they escaped breakdown by most ß-lactamases, due to slow deacylation of the acyl-enzyme intermediate. However, an increasing number of Gram-negative bacteria now produce ß-lactamases with carbapenemase activity: these efficiently hydrolyze the carbapenem ß-lactam ring, severely limiting the treatment of some bacterial infections. Here, we use quantum mechanics/molecular mechanics (QM/MM) simulations of the deacylation reactions of acyl-enzyme complexes of eight ß-lactamases of class A (the most widely distributed ß-lactamase group) with the carbapenem meropenem to investigate differences between those inhibited by carbapenems (TEM-1, SHV-1, BlaC, and CTX-M-16) and those that hydrolyze them (SFC-1, KPC-2, NMC-A, and SME-1). QM/MM molecular dynamics simulations confirm the two enzyme groups to differ in the preferred acyl-enzyme orientation: carbapenem-inhibited enzymes favor hydrogen bonding of the carbapenem hydroxyethyl group to deacylating water (DW). QM/MM simulations of deacylation give activation free energies in good agreement with experimental hydrolysis rates, correctly distinguishing carbapenemases. For the carbapenem-inhibited enzymes, free energies for deacylation are significantly higher than for the carbapenemases, even when the hydroxyethyl group was restrained to prevent interaction with the DW. Analysis of these simulations, and additional simulations of mutant enzymes, shows how factors including the hydroxyethyl orientation, the active site volume, and architecture (conformations of Asn170 and Asn132; organization of the oxyanion hole; and the Cys69-Cys238 disulfide bond) collectively determine catalytic efficiency toward carbapenems.

Development, implementation and evaluation of the online Movement, Interaction and Nutrition for Greater Lifestyles in the Elderly (MINGLE) program: The protocol for a pilot trial.

INTRODUCTION: People with age-related macular degeneration (AMD) are more likely to experience loneliness, have poorer diets and be less physically active than people without AMD. The online Movement, Interaction and Nutrition for Greater Lifestyles in the Elderly (MINGLE) program is a holistic evidence-based intervention aiming to support people with AMD by incorporating physical activity, social interaction and nutrition education components all delivered via a COVID-19-safe Zoom platform. This study will involve two phases: 1) a formative qualitative study with AMD patients to identify the barriers and facilitators to participating in the proposed MINGLE program; and 2) a 10-week pilot study to evaluate the feasibility, acceptability and preliminary efficacy of MINGLE. METHODS AND ANALYSIS: Phase 1 involves AMD patients who will be recruited from an eye clinic in Western Sydney, Australia to participate in audio-recorded semi-structured interviews. Verbatim interview transcripts will be coded using the Capability, Opportunity, Motivation and Behaviour (COM-B) model and themes established. These themes will be used as a guide to specifically tailor the proposed MINGLE program to people with AMD. Phase 2 involves 52 AMD patients who will then be recruited from the same clinic to participate in the MINGLE program. Pre-post questionnaires will be administered to intervention participants to collect information on the following variables: demographics, socioeconomic status, vision function, loneliness, quality of life (including depression), falls risk, physical activity (level), and dietary intake. The acceptability and feasibility of the MINGLE program will also be evaluated using descriptive statistics. TRIAL REGISTRATION NUMBER: ACTRN12621000939897p.