Immunomodulation and fibroblast dynamics driving nociceptive joint pain within inflammatory synovium: Unravelling mechanisms for therapeutic advancements in osteoarthritis.

OBJECTIVE: Synovitis is a widely accepted sign of osteoarthritis (OA), characterised by tissue hyperplasia, where increased infiltration of immune cells and proliferation of resident fibroblasts adopt a pro-inflammatory phenotype, and increased the production of pro-inflammatory mediators that are capable of sensitising and activating sensory nociceptors, which innervate the joint tissues. As such, it is important to understand the cellular composition of synovium and their involvement in pain sensitisation to better inform the development of effective analgesics. METHODS: Studies investigating pain sensitisation in OA with a focus on immune cells and fibroblasts were identified using PubMed, Web of Science and SCOPUS. RESULTS: In this review, we comprehensively assess the evidence that cellular crosstalk between resident immune cells or synovial fibroblasts with joint nociceptors in inflamed OA synovium contributes to peripheral pain sensitisation. Moreover, we explore whether the elucidation of common mechanisms identified in similar joint conditions may inform the development of more effective analgesics specifically targeting OA joint pain. CONCLUSION: The concept of local environment and cellular crosstalk within the inflammatory synovium as a driver of nociceptive joint pain presents a compelling opportunity for future research and therapeutic advancements.

Nanoscopic gel particle for intra-articular injection formulation.

Hyaluronic acid (HA) based nanogels showed effective intracellular delivery efficacy for anti-cancer and anti-inflammatory drugs, characterized by their ability targeting relevant cell receptors. In the present study, we demonstrate the ability of hyaluronic acid-polyethyleneimine (HA-PEI) nanogels as a promising dual-functional interfacial active for intra-articular injection to intervene arthritis. Nanomechanical measurements on both model substrates and human cartilage samples confirm that the HA-PEI nanogels can significantly improve interfacial lubrication, in comparison to HA molecules, or silica-based nanoparticles. We show that the Coefficient of Friction significantly decreases with a decreasing nanogel size. The exceptional lubricating performance, coupled with the proven drug delivery capability, evidences the great potential of nanoscopic hydrogels for early-stage arthritis treatment. The flexibility in choosing the chemical nature, molecular architecture, and structural characteristics of nanogels makes it possible to modulate both drug delivery kinetics and interfacial lubrication, thus representing an innovative approach to treat degenerative joint diseases.

Therapeutic avenues in bone repair: Harnessing an anabolic osteopeptide, PEPITEM, to boost bone growth and prevent bone loss.

The existing suite of therapies for bone diseases largely act to prevent further bone loss but fail to stimulate healthy bone formation and repair. We describe an endogenous osteopeptide (PEPITEM) with anabolic osteogenic activity, regulating bone remodeling in health and disease. PEPITEM acts directly on osteoblasts through NCAM-1 signaling to promote their maturation and formation of new bone, leading to enhanced trabecular bone growth and strength. Simultaneously, PEPITEM stimulates an inhibitory paracrine loop: promoting osteoblast release of the decoy receptor osteoprotegerin, which sequesters RANKL, thereby limiting osteoclast activity and bone resorption. In disease models, PEPITEM therapy halts osteoporosis-induced bone loss and arthritis-induced bone damage in mice and stimulates new bone formation in osteoblasts derived from patient samples. Thus, PEPITEM offers an alternative therapeutic option in the management of diseases with excessive bone loss, promoting an endogenous anabolic pathway to induce bone remodeling and redress the imbalance in bone turnover.

From sabers to spikes: A newfangled reconstruction of the ancient, giant, sexually dimorphic Pacific salmon, †Oncorhynchus rastrosus (SALMONINAE: SALMONINI).

The impressive †Oncorhynchus rastrosus of the Pacific Northwest's Miocene and Pliocene eras was the largest salmonid ever to live. It sported a hypertrophied premaxilla with a pair of enlarged teeth which the original describers reconstructed as projecting ventrally into the mouth, leading them to assign the species to "Smilodonichthys," a genus now in synonymy. Through CT reconstruction of the holotype and newly collected specimens, we demonstrate that the famed teeth projected laterally like tusks, not ventrally like sabers or fangs. We also expand the original description to characterize sexual dimorphism in mature, breeding individuals. Male and female †Oncorhynchus rastrosus differ in the form of the vomer, rostro-dermethmoid-supraethmoid, and dentary, much as do other extant species of Oncorhynchus. Male specimens possess a more elongate vomer than do females, and female vomers have concave ventral surfaces and prominent median dorsal keels. The dentary of females has no evidence of a kype, though some specimens of †O. rastrosus have a non-uniform density mesial to the tooth bed, which we interpret as a male kype. Unlike extant Oncorhynchus, male and female †O. rastrosus do not differ in premaxilla shape. Because male and females possess hypertrophied premaxillae and lateral premaxillary spikes, the former common name "Sabertoothed Salmon" no longer reflects our understanding of the species' morphology. Accordingly, we redub †O. rastrosus the Spike-Toothed Salmon and postulate that its spikes were multifunctional, serving as defense against predators, in agonism against conspecifics, and as a practical aid to nest construction.

The ROSA robotic-arm system reliably restores joint line height, patella height and posterior condylar offset in total knee arthroplasty.

INTRODUCTION: There is growing interest in the use of robotic TKA to improve accuracy of component positioning in Total Knee Arthroplasty (TKA). The aim of this study was to investigate the accuracy of implant component position using the ROSA® knee system with specific reference to Joint Line Height, Patella Height and Posterior Condylar Offset (PCO). METHODS: This was a retrospective review of a prospectively-maintained database of the initial 100 consecutive TKAs performed by a high volume surgeon using the ROSA® knee system. Both the image-based and imageless workflow were used and two prosthesis types were implanted. To determine the accuracy of component positioning, the immediate post-operative radiograph was reviewed and compared with the immediate pre-operative radiograph with regards to Joint Line Height, Patella Height and Posterior Condylar Offset. RESULTS: 100 consecutive patients undergoing TKA using the ROSA system were included; mean age 70 years (range 49-95 years). Mean change in joint line height was 0.2 mm, patella height (Insall-Salvati ratio) 0.01 and posterior condylar offset 0.02 mm; there was no statistically significant difference between the pre and post-operative values. No difference was demonstrated between image-based or imageless workflows, or between implant design (Persona versus Vanguard) regarding joint line height, patella height and PCO. CONCLUSION: This study validates the use of the ROSA® knee system in accurately restoring Joint Line Height, Patella Height and Posterior Condylar Offset in TKA surgery. No significant differences were found between imageless and image-based groups, or between implant designs (Persona versus Vanguard).

Comparative analysis of radiation exposure in robot-assisted total knee arthroplasty using popular robotic systems.

Robotic-assisted TKA (RATKA) is a rapidly emerging technique that has been shown to improve precision and accuracy in implant alignment in TKA. Robotic-assisted TKA (RATKA) uses computer software to create a three-dimensional model of the patient's knee. Different types of preoperative imaging, including radiographs and CT scans, are used to create these models, each with varying levels of radiation exposure. This study aims to determine the radiation dose associated with each type of imaging used in RATKA, to inform patients of the potential risks. A retrospective search of our clinical radiology and arthroplasty database was conducted to identify 140 knees. The patients were divided into three groups based on the type of preoperative imaging they received: (1) CT image-based MAKO Protocol, (2) Antero-posterior long leg alignment films (LLAF), (3) standard AP, lateral, and skyline knee radiographs. The dose of CT imaging technique for each knee was measured using the dose-length product (DLP) with units of mGycm2, whereas the measurement for XRAY images was with the dose area product (DAP) with units of Gycm2. The mean radiation dose for patients in the CT (MAKO protocol) image-based group was 1135 mGy.cm2. The mean radiation dose for patients in the LLAF group was 3081 Gycm2. The mean radiation dose for patients undergoing knee AP/lateral and skyline radiographs was the lowest of the groups, averaging 4.43 Gycm2. Through an ANOVA and post hoc analysis, the results between groups was statistically significant. In this study, we found a significant difference in radiation exposure between standard knee radiographs, LLAF and CT imaging. Nonetheless, the radiation dose for all groups is still within acceptable safety limits.

Robotic trials in arthroplasty surgery.

Total hip and knee arthroplasty (THA, TKA) are largely successful procedures; however, both have variable outcomes, resulting in some patients being dissatisfied with the outcome. Surgeons are turning to technologies such as robotic-assisted surgery in an attempt to improve outcomes. Robust studies are needed to find out if these innovations are really benefitting patients. The Robotic Arthroplasty Clinical and Cost Effectiveness Randomised Controlled Trials (RACER) trials are multicentre, patient-blinded randomized controlled trials. The patients have primary osteoarthritis of the hip or knee. The operation is Mako-assisted THA or TKA and the control groups have operations using conventional instruments. The primary clinical outcome is the Forgotten Joint Score at 12 months, and there is a built-in analysis of cost-effectiveness. Secondary outcomes include early pain, the alignment of the components, and medium- to long-term outcomes. This annotation outlines the need to assess these technologies and discusses the design and challenges when conducting such trials, including surgical workflows, isolating the effect of the operation, blinding, and assessing the learning curve. Finally, the future of robotic surgery is discussed, including the need to contemporaneously introduce and evaluate such technologies.

An evaluation of factors influencing the adoption and usage of robotic surgery in lower limb arthroplasty amongst orthopaedic trainees: a clinical survey.

BACKGROUND: The rise of robotics in orthopaedic training, driven by the demand for better training outcomes and patient care, presents specific challenges for junior trainees due to its novelty and steep learning curve. This paper explores how orthopaedic trainees perceive and adopt robotic-assisted lower limb arthroplasty. METHODS: The study utilised the UTUAT model questionnaire as the primary data collection tool, employing targeted questions on a five-point Likert scale to efficiently gather responses from a large number of participants. Data analysis was conducted using partial least squares (PLS), a well-established method in previous technology acceptance research. RESULT: The findings indicate a favourable attitude amongst trainees towards adopting robotic technology in orthopaedic training. They acknowledge the potential advantages of improved surgical precision and patient outcomes through roboticassisted procedures. Social factors, including the views of peers and mentors, notably influence trainees' decision-making. However, the availability of resources and expert mentors did not appear to have a significant impact on trainees' intention to use robotic technology. CONCLUSION: The study contributes to the understanding of factors influencing trainees' interest in robotic surgery and emphasises the importance of creating a supportive environment for its adoption.

Mako versus ROSA: comparing surgical accuracy in robotic total knee arthroplasty.

There is increasing adoption of robotic surgical technology in Total Knee Arthroplasty. The ROSA® knee system can be used in either image-based mode (using pre-operative calibrated radiographs) or imageless modes (using intra-operative bony registration). The Mako knee system is an image-based system (using a pre-operative CT scan). This study aimed to compare surgical accuracy between the ROSA and Mako systems with specific reference to joint line height, patella height, posterior condylar offset and tibial slope. This was a retrospective review of a prospectively collected data of the initial 50 consecutive ROSA TKAs and the initial 50 consecutive Mako TKAs performed by two high-volume surgeons. To determine the accuracy of component positioning, the immediate post-operative radiograph was reviewed and compared with the immediate pre-operative radiograph with regards to joint line height (JLH), patella height (PH), tibial slope (TS) and posterior condylar offset (PCO). Mean difference between pre- and post-operative radiographs using the ROSA knee system of joint line height was 0.47 mm (SD 0.95) posterior condylar offset 0.16 mm (SD 0.76), tibial slope 0.9 degrees (SD 1.6) and patella height 0.01 (SD 0.05). Mean difference using the MAKO knee system of joint line height was 0.26 (SD 1.08), posterior condylar offset -0.26 mm (SD 0.78), tibial slope 1.8 degrees and patella height 0.03. No significant difference was demonstrated between the accuracy of component positioning of the ROSA or MAKO knee systems. Our study is the first study to compare the accuracy of the ROSA and MAKO knee systems in total knee arthroplasty. Both systems are highly accurate in restoring native posterior condylar offset, joint line height, tibial slope and patella height in TKA with no significant difference demonstrated between the two groups.

What's important for recovery after a total knee replacement? A systematic review of mixed methods studies.

BACKGROUND: Understanding how patients perceive and prioritise various aspects of recovery following total knee replacement, including pain, function and return to activity, will help clinicians in pre-operative consultations by ensuring they effectively address patient concerns and managing their expectations. AIMS: The aim of this study is to identify aspects of recovery that are important to people after a total knee replacement. METHODS: Studies were identified from Medline, Embase, PsycInfo, Cochrane Library and Web of Science. This mixed methods review included all original study types (quantitative, qualitative, discrete choice experiments and mixed methods design). Reviews and non-peer-reviewed publications were excluded. Studies with participants (age ≥ 18 years) who had a primary TKR for osteoarthritis were included. Studies of people with unicompartmental knee, patella-femoral or revision knee replacement were excluded. Recovery attributes were extracted from individual papers and grouped into recovery themes. RESULTS: A total of 23 studies with 8404 participants and 18 recovery themes were developed. The most frequently identified overarching theme was pain, followed by activities of daily living, mobility (walking), recreational activities, specific functional movements of the knee, use of walking aids, sexual activity and range of motion of the knee. Medical complications were an infrequently reported theme, however, was deemed to be high importance. CONCLUSIONS: Reducing pain, returning of activities and daily living and mobility are the three most frequently reported recovery domains for people after TKR. Clinicians should be aware of recovery themes, to ensure they are explored sufficiently when consenting for a TKR. Future research should aim to determine the relative importance of these attributes compared to each other. Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021253699.

The multilevel correlates, contributions, and consequences of leader humility in humanitarian aid work.

Objective: Leader humility has been linked to many positive outcomes but not examined in humanitarian aid work. Three studies examined the multilevel correlates, contributions, and consequences of leader humility in Medair-a large, multinational, faith-based aid organization. Study 1 examined correlates of leader humility in a sample of 308 workers and 167 leaders. Study 2 explored multilevel contributions of leader humility in 96 teams comprised of 189 workers. Study 3 utilized a subsample (50 workers, 34 leaders) to explore consequences of Time 1 leader and team humility on outcomes 6 months later. Method: Participants completed measures of humility (general, relational, team), leader and team attributions (e.g., effectiveness, cohesion, and growth-mindedness), organizational outcomes (e.g., job engagement and satisfaction; worker and team performance), and psychological outcomes (e.g., depression, anxiety, compassion satisfaction, and flourishing). Results: Leader and team humility contributed to multilevel positive attributions about leaders (as effective and impactful), teams (as cohesive, psychologically safe, and growth-minded), and oneself (as humble), and those attributions contributed to organizational and psychological outcomes. Teams' shared attributions of their leader's humility contributed to higher worker job satisfaction and team performance. Longitudinally, for workers and leaders, leader and team humility were associated with some positive organizational and psychological outcomes over time. Conclusion: In humanitarian organizations, leader humility seems to act as an attributional and motivational social contagion that affects aid personnel's positive attributions about their leaders, teams, and themselves. In turn, these multilevel positive attributions contribute to several positive team, organizational, and psychological outcomes among workers and leaders.

Andy Golden: Mentorship through the Years.

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UK robotic arthroplasty clinical and cost effectiveness randomised controlled trial for hips (RACER-Hip): a study protocol.

INTRODUCTION: The number of robotic-assisted hip replacement procedures has expanded globally with the intended aim of improving outcomes. Intraoperative robotic-arm systems add additional costs to total hip replacement (THR) surgery but may improve surgical precision and could contribute to diminished pain and improved function. Additionally, these systems may reduce the need for expensive revision surgery. Surgery with conventional instruments may be just as successful, quick and affordable. There is timely demand for a robust evaluation of this technology. METHODS AND ANALYSIS: The Robotic Arthroplasty Clinical and cost Effectiveness Randomised controlled trial for Hips (RACER-Hip) is a multicentre (minimum of six UK sites), participant-assessor blinded, randomised controlled trial. 378 participants with hip osteoarthritis requiring THR will be randomised (1:1) to receive robotic-assisted THR, or THR using conventional surgical instruments. The primary outcome is the Forgotten Joint Score at 12 months post-randomisation; a patient-reported outcome measure assessing participants' awareness of their joint when undertaking daily activities. Secondary outcomes will be collected post-operatively (pain, blood loss and opioid usage) and at 3, 6, 12, 24 months, then 5 and 10 years postrandomisation (including function, pain, health-related quality of life, reoperations and satisfaction). Allocation concealment will be accomplished using a computer-based randomisation procedure on the day of surgery. Blinding methods include the use of sham incisions for marker clusters and blinded operation notes. The primary analysis will adhere to the intention-to-treat principle. Results will adhere to Consolidated Standards of Reporting Trials statements. ETHICS AND DISSEMINATION: The trial was approved by an ethics committee (Solihull Research Ethics Committee, 30 June 2021, IRAS: 295831). Participants will provide informed consent before agreeing to participate. Results will be disseminated using peer-reviewed journal publications, presentations at international conferences and through the use of social media. We will develop plans to disseminate to patients and public with our patient partners. TRIAL REGISTRATION NUMBER: ISRCTN13374625.

Identification of rare microbial colonizers of plastic materials incubated in a coral reef environment.

Plastic waste accumulation in marine environments has complex, unintended impacts on ecology that cross levels of community organization. To measure succession in polyolefin-colonizing marine bacterial communities, an in situ time-series experiment was conducted in the oligotrophic coastal waters of the Bermuda Platform. Our goals were to identify polyolefin colonizing taxa and isolate bacterial cultures for future studies of the biochemistry of microbe-plastic interactions. HDPE, LDPE, PP, and glass coupons were incubated in surface seawater for 11 weeks and sampled at two-week intervals. 16S rDNA sequencing and ATR-FTIR/HIM were used to assess biofilm community structure and chemical changes in polymer surfaces. The dominant colonizing taxa were previously reported cosmopolitan colonizers of surfaces in marine environments, which were highly similar among the different plastic types. However, significant differences in rare community composition were observed between plastic types, potentially indicating specific interactions based on surface chemistry. Unexpectedly, a major transition in community composition occurred in all material treatments between days 42 and 56 (p < 0.01). Before the transition, Alteromonadaceae, Marinomonadaceae, Saccharospirillaceae, Vibrionaceae, Thalassospiraceae, and Flavobacteriaceae were the dominant colonizers. Following the transition, the relative abundance of these taxa declined, while Hyphomonadaceae, Rhodobacteraceae and Saprospiraceae increased. Over the course of the incubation, 8,641 colonizing taxa were observed, of which 25 were significantly enriched on specific polyolefins. Seven enriched taxa from families known to include hydrocarbon degraders (Hyphomonadaceae, Parvularculaceae and Rhodobacteraceae) and one n-alkane degrader (Ketobacter sp.). The ASVs that exhibited associations with specific polyolefins are targets of ongoing investigations aimed at retrieving plastic-degrading microbes in culture.

Sulforaphane Bioavailability in Healthy Subjects Fed a Single Serving of Fresh Broccoli Microgreens.

Cruciferous vegetable consumption is associated with numerous health benefits attributed to the phytochemical sulforaphane (SFN) that exerts antioxidant and chemopreventive properties, among other bioactive compounds. Broccoli sprouts, rich in SFN precursor glucoraphanin (GRN), have been investigated in numerous clinical trials. Broccoli microgreens are similarly rich in GRN but have remained largely unexplored. The goal of this study was to examine SFN bioavailability and the microbiome profile in subjects fed a single serving of fresh broccoli microgreens. Eleven subjects participated in a broccoli microgreens feeding study. Broccoli microgreens GRN and SFN contents and stability were measured. Urine and stool SFN metabolite profiles and microbiome composition were examined. Broccoli microgreens had similar GRN content to values previously reported for broccoli sprouts, which was stable over time. Urine SFN metabolite profiles in broccoli microgreens-fed subjects were similar to those reported previously in broccoli sprouts-fed subjects, including the detection of SFN-nitriles. We also reported the detection of SFN metabolites in stool samples for the first time. A single serving of broccoli microgreens did not significantly alter microbiome composition. We showed in this study that broccoli microgreens are a significant source of SFN. Our work provides the foundation for future studies to establish the health benefits of broccoli microgreens consumption.

Defining the optimal position of the lipped liner in combination with cup orientation and stem version.

Aims: The aim of this study was to identify the optimal lip position for total hip arthroplasties (THAs) using a lipped liner. There is a lack of consensus on the optimal position, with substantial variability in surgeon practice. Methods: A model of a THA was developed using a 20° lipped liner. Kinematic analyses included a physiological range of motion (ROM) analysis and a provocative dislocation manoeuvre analysis. ROM prior to impingement was calculated and, in impingement scenarios, the travel distance prior to dislocation was assessed. The combinations analyzed included nine cup positions (inclination 30-40-50°, anteversion 5-15-25°), three stem positions (anteversion 0-15-30°), and five lip orientations (right hip 7 to 11 o'clock). Results: The position of the lip changes the ROM prior to impingement, with certain combinations leading to impingement within the physiological ROM. Inferior lip positions (7 to 8 o'clock) performed best with cup inclinations of 30° and 40°. Superior lip positions performed best with cup inclination of 50°. When impingement occurs in the plane of the lip, the lip increases the travel distance prior to dislocation. Inferior lip positions led to the largest increase in jump distance in a posterior dislocation provocation manoeuvre. Conclusion: The lip orientation that provides optimal physiological ROM depends on the orientation of the cup and stem. For a THA with stem anteversion 15°, cup inclination 40°, and cup anteversion 15°, the optimal lip position was posterior-inferior (8 o'clock). Maximizing jump distance prior to dislocation while preventing impingement in the opposite direction is possible with appropriate lip positioning.

Pre-Younger Dryas megafaunal extirpation at Rancho La Brea linked to fire-driven state shift.

The cause, or causes, of the Pleistocene megafaunal extinctions have been difficult to establish, in part because poor spatiotemporal resolution in the fossil record hinders alignment of species disappearances with archeological and environmental data. We obtained 172 new radiocarbon dates on megafauna from Rancho La Brea in California spanning 15.6 to 10.0 thousand calendar years before present (ka). Seven species of extinct megafauna disappeared by 12.9 ka, before the onset of the Younger Dryas. Comparison with high-resolution regional datasets revealed that these disappearances coincided with an ecological state shift that followed aridification and vegetation changes during the Bølling-Allerød (14.69 to 12.89 ka). Time-series modeling implicates large-scale fires as the primary cause of the extirpations, and the catalyst of this state shift may have been mounting human impacts in a drying, warming, and increasingly fire-prone ecosystem.

Robotic Arthroplasty Clinical and cost Effectiveness Randomised controlled trial (RACER-knee): a study protocol.

INTRODUCTION: Robotic-assisted knee replacement systems have been introduced to healthcare services worldwide in an effort to improve clinical outcomes for people, although high-quality evidence that they are clinically, or cost-effective remains sparse. Robotic-arm systems may improve surgical accuracy and could contribute to reduced pain, improved function and lower overall cost of total knee replacement (TKR) surgery. However, TKR with conventional instruments may be just as effective and may be quicker and cheaper. There is a need for a robust evaluation of this technology, including cost-effectiveness analyses using both within-trial and modelling approaches. This trial will compare robotic-assisted against conventional TKR to provide high-quality evidence on whether robotic-assisted knee replacement is beneficial to patients and cost-effective for healthcare systems. METHODS AND ANALYSIS: The Robotic Arthroplasty Clinical and cost Effectiveness Randomised controlled trial-Knee is a multicentre, participant-assessor blinded, randomised controlled trial to evaluate the clinical and cost-effectiveness of robotic-assisted TKR compared with TKR using conventional instruments. A total of 332 participants will be randomised (1:1) to provide 90% power for a 12-point difference in the primary outcome measure; the Forgotten Joint Score at 12 months postrandomisation. Allocation concealment will be achieved using computer-based randomisation performed on the day of surgery and methods for blinding will include sham incisions for marker clusters and blinded operation notes. The primary analysis will adhere to the intention-to-treat principle. Results will be reported in line with the Consolidated Standards of Reporting Trials statement. A parallel study will collect data on the learning effects associated with robotic-arm systems. ETHICS AND DISSEMINATION: The trial has been approved by an ethics committee for patient participation (East Midlands-Nottingham 2 Research Ethics Committee, 29 July 2020. NRES number: 20/EM/0159). All results from the study will be disseminated using peer-reviewed publications, presentations at international conferences, lay summaries and social media as appropriate. TRIAL REGISTRATION NUMBER: ISRCTN27624068.

Religion/Spirituality, Stress, and Resilience Among Sexual and Gender Minorities: The Religious/Spiritual Stress and Resilience Model.

Although many sexual and gender minorities (SGMs) consider themselves religious or spiritual, the impact of this religiousness or spirituality (RS) on their health is poorly understood. We introduce the religious/spiritual stress and resilience model (RSSR) to provide a robust framework for understanding the variegated ways that RS influences the health of SGMs. The RSSR bridges existing theorizing on minority stress, structural stigma, and RS-health pathways to articulate the circumstances under which SGMs likely experience RS as health promoting or health damaging. The RSSR makes five key propositions: (a) Minority stress and resilience processes influence health; (b) RS influences general resilience processes; (c) RS influences minority-specific stress and resilience processes; (d) these relationships are moderated by a number of variables uniquely relevant to RS among SGMs, such as congregational stances on same-sex sexual behavior and gender expression or an individual's degree of SGM and RS identity integration; and (e) relationships between minority stress and resilience, RS, and health are bidirectional. In this manuscript, we describe the empirical basis for each of the five propositions focusing on research examining the relationship between RS and health among SGMs. We conclude by describing how the RSSR may inform future research on RS and health among SGMs.