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Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of the motor neurons that innervate muscle, resulting in gradual paralysis and culminating in the inability to breathe or swallow. This neuronal degeneration occurs in a spatiotemporal manner from a point of onset in the central nervous system (CNS), suggesting that there is a molecule that spreads from cell-to-cell. There is strong evidence that the onset and progression of ALS pathology is a consequence of protein misfolding and aggregation. In line with this, a hallmark pathology of ALS is protein deposition and inclusion formation within motor neurons and surrounding glia of the proteins TAR DNA-binding protein 43, superoxide dismutase-1, or fused in sarcoma. Collectively, the observed protein aggregation, in conjunction with the spatiotemporal spread of symptoms, strongly suggests a prion-like propagation of protein aggregation occurs in ALS. In this review, we discuss the role of protein aggregation in ALS concerning protein homeostasis (proteostasis) mechanisms and prion-like propagation. Furthermore, we examine the experimental models used to investigate these processes, including in vitro assays, cultured cells, invertebrate models, and murine models. Finally, we evaluate the therapeutics that may best prevent the onset or spread of pathology in ALS and discuss what lies on the horizon for treating this currently incurable disease.

Live attenuated bacterial vectors, such as Salmonella typhimurium, have shown promise as delivery vehicles for DNA. We have examined two new strains of S. typhimurium and their impact on dendritic cell maturation (CD12-sifA/aroC mutant and WT05-ssaV/aroC, both in TML background). Strain WT05 matured dendritic cells in a more efficient way; caused higher release of cytokines TNF-α, IL-12, IL-1β; and was efficient for gene transfer. These findings suggest that the genetic background of the attenuation can influence the pattern of inflammatory immune response to Salmonella infection.

With the onset of the rapidly ageing population, the impact of age related neurodegenerative diseases is becoming a predominant health and economic concern. Neurodegenerative diseases such as Alzheimer’s disease, Creutzfeldt-Jakob disease, Parkinson’s disease, Huntington’s disease, frontotemporal dementia and amyotrophic lateral sclerosis result from the loss of a specific subsets of neurons, which is closely associated with accumulation and deposition of specific protein aggregates. Protein aggregation, or fibril formation, is a well-studied phenomenon that occurs in a nucleation-dependent growth reaction. Recently, there has been a swell of literature implicating protein aggregation and its ability to propagate cell-to-cell in the rapid progression of these diseases. In order for protein aggregation to be kindled in recipient cells it is a requisite that aggregates must be able to be released from one cell and then taken up by others. In this article we will explore the relationship between protein aggregates, their propagation and the role of macropinocytosis in their uptake. We highlight the ability of neurons to undergo stimulated macropinocytosis and identify potential therapeutic targets.

Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores.

Abstract Accurate detection and tracking of animals across diverse environments are crucial for studying brain and behavior. Recently, computer vision techniques have become essential for high-throughput behavioral studies; however, localizing animals in complex conditions remains challenging due to intra-class visual variability and environmental diversity. These challenges hinder studies in naturalistic settings, such as when animals are partially concealed within nests. Moreover, current tools are laborious and time-consuming, requiring extensive, setup-specific annotation and training procedures. To address these challenges, we introduce the 'Detect-Any-Mouse-Model' (DAMM), an object detector for localizing mice in complex environments with minimal training. Our approach involved collecting and annotating a diverse dataset of single- and multi-housed mice in complex setups. We trained a Mask R-CNN, a popular object detector in animal studies, to perform instance segmentation and validated DAMM’s performance on a collection of downstream datasets using zero-shot and few-shot inference. DAMM excels in zero-shot inference, detecting mice and even rats, in entirely unseen scenarios and further improves with minimal training. Using the SORT algorithm, we demonstrate robust tracking, competitive with keypoint-estimation-based methods. Notably, to advance and simplify behavioral studies, we release our code, model weights, and data, along with a user-friendly Python API and a Google Colab implementation.

Abstract Natural ecosystems store large amounts of carbon globally, as organisms absorb carbon from the atmosphere to build large, long-lasting, or slow-decaying structures such as tree bark or root systems. An ecosystem’s carbon sequestration potential is tightly linked to its biological diversity. Yet when considering future projections, many carbon sequestration models fail to account for the role biodiversity plays in carbon storage. Here, we assess the consequences of plant biodiversity loss for carbon storage under multiple climate and land-use change scenarios. We link a macroecological model projecting changes in vascular plant richness under different scenarios with empirical data on relationships between biodiversity and biomass. We find that biodiversity declines from climate and land use change could lead to a global loss of between 7.44-103.14 PgC (global sustainability scenario) and 10.87-145.95 PgC (fossil-fueled development scenario). This indicates a self-reinforcing feedback loop, where higher levels of climate change lead to greater biodiversity loss, which in turn leads to greater carbon emissions and ultimately more climate change. Conversely, biodiversity conservation and restoration can help achieve climate change mitigation goals.

Meat Standards Australia (MSA) sensory protocols have been effectively utilized in beef for international consumers employing several cooking methods. Our objective was to compare the consumer response of Australian and American consumers to paired beef brisket samples utilizing a newly developed low and slow cooking method. Briskets were collected from Australian carcasses with diverse eating quality. Half of the briskets (n = 24) were retained in Australia and their pair was exported to Texas for consumer sensory testing. Naïve consumers (Australia; n = 240) and familiar consumers (USA; n = 240) evaluated paired barbequed briskets for tenderness, juiciness, flavor liking, and overall liking from 0 to 100 using a visual analogue scale, and a weighted composite meat quality score was later calculated. Australian consumers scored briskets lower for tenderness (−4.84 ± 1.70 points) and juiciness (−4.44 ± 1.55 points) and higher for flavor liking (3.48 ± 1.58 points); however, there was no difference between the countries for overall liking (p = 0.75) and combined meat quality score (p = 0.88). Differences between Australian and US consumers’ evaluations indicate that there is an impact of cultural background, potentially driven by Australia’s naivety to the low and slow barbeque cooking method.

Abstract Internalization of complement membrane attack complexes (MACs) assembles NLRP3 inflammasomes in endothelial cells (EC) and promotes IL-β-mediated tissue inflammation. Informed by proteomics analyses of FACS-sorted inflammasomes, we identify a protein complex modulating inflammasome activity on endosomes. ZFVYE21, a Rab5 effector, partners with Rubicon and RNF34, forming a “ZRR” complex that is stabilized in a Rab5- and ZFYVE21-dependent manner on early endosomes. There, Rubicon competitively disrupts inhibitory associations between caspase-1 and its pseudosubstrate, Flightless I (FliI), while RNF34 ubiquitinylates and degradatively removes FliI from the signaling endosome. The concerted actions of the ZRR complex increase pools of endosome-associated caspase-1 available for activation. The ZRR complex is assembled in human tissues, its associated signaling responses occur in three mouse models in vivo, and the ZRR complex promotes inflammation in a skin model of chronic rejection. The ZRR signaling complex reflects a potential therapeutic target for attenuating inflammasome-mediated tissue injury.

Virtual healthcare has the potential to increase access to allied health for people living in rural areas, but challenges in delivery of such models have been reported. The COVID-19 pandemic provided an opportunity for a rural practice of physiotherapists and exercise physiologists to transition service delivery to a virtual model of care which utilised a combination of phone, video, an exercise app and/or paper handouts. This study aimed to evaluate the uptake and outcomes from virtual delivery of allied health services, and to describe patient and clinician experiences of the virtual model of care. A parallel convergent mixed methods study was conducted. De-identified data from patients who were offered the virtual service between 15 March 2020 and 30 September 2020 were extracted from the database of the rural practice, as were data from patients attending the practice in-person during the same time in 2019 to serve as a historical comparison. De-identified data from a monthly survey tracking clinician experiences of delivering care virtually was also obtained from the practice. Quantitative data were presented descriptively. Between-group differences were compared using independent samples t-tests, and within-group longitudinal changes compared using paired t-tests. Semi-structured interviews were conducted among a purposive sample of patients using the virtual service, and focus groups conducted among clinicians providing this model of care. Qualitative data were recorded and transcribed verbatim, then thematic analysis conducted. During the study period, the practice delivered 4% (n = 242) consultations virtually. Thirty-seven of the 60 patients (62%) using the virtual service were new referrals. Patients attended fewer sessional appointments virtually and a smaller proportion of patients reported high satisfaction with virtual care, compared to those who received in-person care the previous year (p < .05). Clinician confidence in delivering virtual care did not change significantly over time (p>.05), though clinicians not providing virtual care in a given month perceived their lower confidence than those who did provide virtual care (p < .05). Five themes influencing the success of virtual allied health provision emerged from patient interviews and clinician focus groups: adaptation of program elements for virtual delivery, conduct of virtual treatment, clinician flexibility, patient complexity and communication. The theme of communication influenced all the other themes. Virtual healthcare is a potential solution to address lack of access to allied health practitioners in rural areas, but may not suit all patients. Establishing a therapeutic relationship and ensuring people have access to adequate resources prior to virtual care delivery will optimise successful adoption of virtual care models. A hybrid model incorporating limited in-person consultations with virtual consultations appears a more viable option.

Abstract Changing seasonal precipitation patterns prompted by climate change are likely causing increasing degradation of adobe architecture in the American Southwest. This deterioration includes surface erosion and catastrophic collapse. This study examines the impact of changing rainfall patterns on untreated adobe walls to understand how damage occurs and anticipate future impacts. To complete the study, we constructed 20 adobe test walls. Using a portable rain simulator, each wall was subjected to two rainfall experiments: high-intensity rainfall simulations (rain intensity variable) and low-intensity rainfall simulations (rain event number variable). Wall-degradation metrics (material loss, volume loss, affected surface area, and cavity depth) were calculated for each wall using pre- and post-simulation LiDAR scans. Internal wall moisture was also measured with embedded volumetric water content sensors. In the high-intensity experiment, the lines of best-fit for material loss and affected surface area show that surface erosion increases with rain intensity, while cavity depth remains consistent. Linear models and post-hoc tests indicate material loss and affected surface area is significantly different for each high-intensity rainfall treatment. Furthermore, the interior of each wall remained relatively dry demonstrating that rain intensity is not a strong predictor of interior wall moisture. In the low-intensity rainfall experiment, the rainfall simulations yielded statistically similar erosion and interior wall moisture results. Greater infiltration occurred under low-intensity long-duration rain conditions, while greater surficial damage occurred under high-intensity rain conditions. In conclusion, changing weather regimes are bringing more intense rainfall events to the arid American Southwest. This study suggests that more frequent high intensity rain events will cause increasing damage to adobe walls. Resource managers will need to adapt current management strategies to account for this change.

Pets often factor in older adults’ health behaviors and decisions. However, the degree to which issues related to pet ownership are encountered or addressed by professionals working with this population remains unknown. The aim of this study was to identify specific issues stemming from pet ownership professionals had encountered in their work with older adults, people living with dementia, and care partners. An interdisciplinary (e.g., social services and healthcare) sample (N = 462, 89.13% female, Mage = 53.02, SDage = 12.18) completed an online survey addressing pet ownership issues encountered in their work. Descriptive statistics, t-tests, and repeated measures ANOVAs were used to analyze quantitative data. A conventional content analysis was used to analyze open-ended responses to an item asking about “other” issues encountered in their work with these populations. The professionals estimated 46.29% of clients had been pet owners, 41.23% regularly asked about pets, and 79.22% had encountered issues related to pet ownership. Specific issues raised to the professionals varied by type of client. The professionals reported older adults most often raised getting pet items into the home and concerns about their pets’ health. The issues most often raised by people living with dementia to the professionals were planning for the pet due to a housing transition and basic pet care. Care partners focused on basic pet care and planning for the pet due to a housing transition. The professionals themselves most often raised the issues of basic pet care, concerns about falling, and the pets’ behavior. Professionals who entered clients’ homes were more likely to raise issues stemming from pet ownership compared to those who reported they did not enter clients’ homes in their current job, t(429.40) = 5.59, p < 0.00001. The eleven new issues identified by the content analysis (e.g., pets impeding care, people refusing care due to the pet) underscored how the health and wellbeing of people and their pets are linked. The results of this study provide strong evidence that professionals do encounter issues related to pet ownership. Including issues stemming from pet ownership into procedures, policies, and programs is likely to have positive impacts on those served by and working in the geriatric workforce.

Abstract Background Individuals with Down syndrome are likely to develop clinical and neuropathological brain changes resembling Alzheimer’s disease dementia by the ages of 35–40 years. Intranasal insulin is a potential treatment for neurodegenerative disease that has been shown to reduce amyloid plaque burden and improve verbal memory performance in normal as well as memory-impaired adults. Investigations have shown that rapid-acting insulins may result in superior cognitive benefits compared with regular insulin. Objectives The primary objective of this study was to measure the safety and feasibility of intranasal rapid-acting glulisine in subjects with Down syndrome. Secondarily, we estimated the effects of intranasal glulisine on cognition and memory in Down syndrome. Methods A single-center, single-dose, randomized, double-blind, placebo-controlled, cross-over pilot study was performed to test the safety of intranasal glulisine vs placebo in 12 subjects with Down syndrome aged ≥ 35 years. Intranasal administration utilized the Impel NeuroPharma I109 Precision Olfactory Delivery (POD®) device. The primary outcomes were the occurrence of any or related adverse and serious adverse events. Secondary post-treatment cognitive outcome measures included performance on the Fuld Object-Memory Evaluation and Rivermead Behavioral Memory Test. Results Intranasal glulisine was safe and well tolerated in the Down syndrome population. No adverse or serious adverse events were observed. Conclusions Further investigations are necessary to better evaluate the potential cognitive-enhancing role of intranasal insulin in the Down syndrome population. ClinicalTrials.gov ID NCT02432716.

The BYU library implemented a Machine Learning-based tool to perform various text analysis tasks on transcripts of chat-based interactions between patrons and librarians. These text analysis tasks included estimating patron satisfaction and classifying queries into various categories such as Research/Reference, Directional, Tech/Troubleshooting, Policy/Procedure, and others. An accuracy of 78% or better was achieved for each category. This paper details the implementation details and explores potential applications for the text analysis tool.

Abstract Written from a dyadic strength‐based perspective, this article first provides a brief overview of the Education, Information, and Support section of the 2018 Alzheimer's Disease Dementia Care Practice Recommendations.1 Subsequent sections present a comprehensive overview of available valid and reliable psychosocial measures that assess a selection of important domains for dementia care planning that can be used by families from early stage until end‐of‐life. Measures selected for the purposes of this article will focus on concepts that are strength‐based and most relevant to care dyads as they navigate the difficult disease trajectory: readiness, knowledge, coping, dyadic relationship, care values and preferences. We will also highlight measures that have traditionally targeted the family care partner but can potentially be considered for use with the care partner with dementia, with adjustments, beyond the early stages. Part of this discussion will include various strategies for including persons with dementia in all aspects of their own care using a strength‐based perspective, potentially enabling them to answer questions more reliably across disease stages. Last, gaps in existing measures will be identified to provide options to better assess areas of need most meaningful to families, and in ways that positively contribute to the successful aging of those living with dementia and their care partners.

Ocean acidification is a growing environmental problem, and there is a need to investigate how the decreasing pH will affect marine organisms. Here we studied the effects of lowered pH on the growth and development of the threespine stickleback (Gasterosteus aculeatus) eggs. Adult fish, collected from the natural environment, were allowed to mate in aquaria and the newly produced eggs were incubated in an experiment. Eggs and larvae from ambient conditions (produced in the laboratory) were reared at three different pH concentrations (control: pH 7.8; and reduced pH treatments: pH 7.5 and 7.0) for 21 days in the laboratory. Dissolved oxygen concentration (8.1 ± 0.1 mg l−1) and temperature (18.6 ± 0.02°C) were monitored regularly. Then, egg diameter, larval length, weight and survival were measured. There was no relationship between egg diameter and pH or oxygen, but a negative relationship was found with temperature. Survival of larvae was not affected by pH or temperature, whereas dissolved oxygen concentration had a positive effect on number of survivors. The pH did not have a significant effect on the final larval length on day 21, but interacted significantly with dissolved oxygen. Higher temperatures were found to have a positive effect on the final larval length and weight. Larval weight, on the other hand, was not related to pH nor oxygen. Coastal zones are characterized by pH levels that fluctuate due to natural processes, such as upwelling and river runoff. Our results suggest that the threespine stickleback larvae are well adapted to the different pHs tested, and egg development will likely not be affected by decreasing pH, but even slight temperature and oxygen changes can have a great impact on the threespine stickleback development.

Mariprofundus ferrooxydans PV-1 has provided the first genome of the recently discovered Zetaproteobacteria subdivision. Genome analysis reveals a complete TCA cycle, the ability to fix CO(2), carbon-storage proteins and a sugar phosphotransferase system (PTS). The latter could facilitate the transport of carbohydrates across the cell membrane and possibly aid in stalk formation, a matrix composed of exopolymers and/or exopolysaccharides, which is used to store oxidized iron minerals outside the cell. Two-component signal transduction system genes, including histidine kinases, GGDEF domain genes, and response regulators containing CheY-like receivers, are abundant and widely distributed across the genome. Most of these are located in close proximity to genes required for cell division, phosphate uptake and transport, exopolymer and heavy metal secretion, flagellar biosynthesis and pilus assembly suggesting that these functions are highly regulated. Similar to many other motile, microaerophilic bacteria, genes encoding aerotaxis as well as antioxidant functionality (e.g., superoxide dismutases and peroxidases) are predicted to sense and respond to oxygen gradients, as would be required to maintain cellular redox balance in the specialized habitat where M. ferrooxydans resides. Comparative genomics with other Fe(II) oxidizing bacteria residing in freshwater and marine environments revealed similar content, synteny, and amino acid similarity of coding sequences potentially involved in Fe(II) oxidation, signal transduction and response regulation, oxygen sensation and detoxification, and heavy metal resistance. This study has provided novel insights into the molecular nature of Zetaproteobacteria.

BackgroundColonisation of sessile eukaryotic host surfaces (e.g. invertebrates and seaweeds) by bacteria is common in the marine environment and is expected to create significant inter-species competition and other interactions. The bacterium Pseudoalteromonas tunicata is a successful competitor on marine surfaces owing primarily to its ability to produce a number of inhibitory molecules. As such P. tunicata has become a model organism for the studies into processes of surface colonisation and eukaryotic host-bacteria interactions.Methodology/principal findingsTo gain a broader understanding into the adaptation to a surface-associated life-style, we have sequenced and analysed the genome of P. tunicata and compared it to the genomes of closely related strains. We found that the P. tunicata genome contains several genes and gene clusters that are involved in the production of inhibitory compounds against surface competitors and secondary colonisers. Features of P. tunicata's oxidative stress response, iron scavenging and nutrient acquisition show that the organism is well adapted to high-density communities on surfaces. Variation of the P. tunicata genome is suggested by several landmarks of genetic rearrangements and mobile genetic elements (e.g. transposons, CRISPRs, phage). Surface attachment is likely to be mediated by curli, novel pili, a number of extracellular polymers and potentially other unexpected cell surface proteins. The P. tunicata genome also shows a utilisation pattern of extracellular polymers that would avoid a degradation of its recognised hosts, while potentially causing detrimental effects on other host types. In addition, the prevalence of recognised virulence genes suggests that P. tunicata has the potential for pathogenic interactions.Conclusions/significanceThe genome analysis has revealed several physiological features that would provide P. tunciata with competitive advantage against other members of the surface-associated community. We have also identified properties that could mediate interactions with surfaces other than its currently recognised hosts. This together with the detection of known virulence genes leads to the hypothesis that P. tunicata maintains a carefully regulated balance between beneficial and detrimental interactions with a range of host surfaces.

Prochlorococcus is a marine cyanobacterium that numerically dominates the mid-latitude oceans and is the smallest known oxygenic phototroph. Numerous isolates from diverse areas of the world's oceans have been studied and shown to be physiologically and genetically distinct. All isolates described thus far can be assigned to either a tightly clustered high-light (HL)-adapted clade, or a more divergent low-light (LL)-adapted group. The 16S rRNA sequences of the entire Prochlorococcus group differ by at most 3%, and the four initially published genomes revealed patterns of genetic differentiation that help explain physiological differences among the isolates. Here we describe the genomes of eight newly sequenced isolates and combine them with the first four genomes for a comprehensive analysis of the core (shared by all isolates) and flexible genes of the Prochlorococcus group, and the patterns of loss and gain of the flexible genes over the course of evolution. There are 1,273 genes that represent the core shared by all 12 genomes. They are apparently sufficient, according to metabolic reconstruction, to encode a functional cell. We describe a phylogeny for all 12 isolates by subjecting their complete proteomes to three different phylogenetic analyses. For each non-core gene, we used a maximum parsimony method to estimate which ancestor likely first acquired or lost each gene. Many of the genetic differences among isolates, especially for genes involved in outer membrane synthesis and nutrient transport, are found within the same clade. Nevertheless, we identified some genes defining HL and LL ecotypes, and clades within these broad ecotypes, helping to demonstrate the basis of HL and LL adaptations in Prochlorococcus. Furthermore, our estimates of gene gain events allow us to identify highly variable genomic islands that are not apparent through simple pairwise comparisons. These results emphasize the functional roles, especially those connected to outer membrane synthesis and transport that dominate the flexible genome and set it apart from the core. Besides identifying islands and demonstrating their role throughout the history of Prochlorococcus, reconstruction of past gene gains and losses shows that much of the variability exists at the "leaves of the tree," between the most closely related strains. Finally, the identification of core and flexible genes from this 12-genome comparison is largely consistent with the relative frequency of Prochlorococcus genes found in global ocean metagenomic databases, further closing the gap between our understanding of these organisms in the lab and the wild.

Owing to their phylogenetic position, cartilaginous fishes (sharks, rays, skates, and chimaeras) provide a critical reference for our understanding of vertebrate genome evolution. The relatively small genome of the elephant shark, Callorhinchus milii, a chimaera, makes it an attractive model cartilaginous fish genome for whole-genome sequencing and comparative analysis. Here, the authors describe survey sequencing (1.4x coverage) and comparative analysis of the elephant shark genome, one of the first cartilaginous fish genomes to be sequenced to this depth. Repetitive sequences, represented mainly by a novel family of short interspersed element-like and long interspersed element-like sequences, account for about 28% of the elephant shark genome. Fragments of approximately 15,000 elephant shark genes reveal specific examples of genes that have been lost differentially during the evolution of tetrapod and teleost fish lineages. Interestingly, the degree of conserved synteny and conserved sequences between the human and elephant shark genomes are higher than that between human and teleost fish genomes. Elephant shark contains putative four Hox clusters indicating that, unlike teleost fish genomes, the elephant shark genome has not experienced an additional whole-genome duplication. These findings underscore the importance of the elephant shark as a critical reference vertebrate genome for comparative analysis of the human and other vertebrate genomes. This study also demonstrates that a survey-sequencing approach can be applied productively for comparative analysis of distantly related vertebrate genomes.

Instruksi merupakan faktor penting yang dapat mempengaruhi keberhasilan perawatan gigi tiruan lengkap. Leaflet merupakan salah satu media tulis yang seringkali digunakan dalam penyampaian informasi dan instruksi. Pemberian instruksi yang baik dapat meningkatkan perilaku pembersihan sehingga akan mempengaruhi kualitas hidup. Penelitian ini dilaksanakan dengan tujuan untuk mengetahui pengaruh pemberian instruksi pembersihan gigi tiruan lengkap dengan menggunakan leaflet terhadap kualitas hidup terkait kebersihan rongga mulut pada lansia pengguna gigi tiruan lengkap. Jenis penelitian ini adalah eksperimental dengan desain one group pre-test dan post-test yang dilakukan di Panti Wreda Kasih Bapa, Pontianak Tenggara dengan mewawancarai 36 pasien dengan menggunakan kuesioner OHIP-EDENT. Pengumpulan data dilakukan sebanyak 2 kali yaitu sebelum diberikan instruksi leaflet dan 1 bulan setelah diberikan instruksi leaflet. Hasil penelitian menunjukkan adanya perubahan kualitas hidup pada lansia setelah diberikan instruksi pembersihan gigi tiruan dengan menggunakan leaflet. Sebelum diberikan instruksi ditemukan bahwa mayoritas pasien di Panti Wreda Kasih Bapa memiliki kualitas hidup sedang (86,11%). Setelah diberikan instruksi terdapat peningkatan dimana mayoritas pasien memiliki kualitas hidup baik (55,56%). Hasil uji Wilcoxon Signed Rank didapatkan nilai p=0,000. Disimpulkan terdapat pengaruh pemberian instruksi leaflet pembersihan gigi tiruan lengkap terhadap kualitas hidup terkait kebersihan rongga mulut pada lansia pengguna gigi tiruan lengkap.