Utilization of geospatial distribution in the measurement of study cohort representativeness.

OBJECTIVE: The ability to apply results from a study to a broader population remains a primary objective in translational science. Distinct from intrinsic elements of scientific rigor, the extrinsic concept of generalization requires there be alignment between a study cohort and population in which results are expected to be applied. Widespread efforts have been made to quantify representativeness of study cohorts. These techniques, however, often consider the study and target cohorts as monolithic collections that can be directly compared. Overlooking known impacts to health from socio-demographic and environmental factors tied to individual's geographical location, and potentially obfuscating misalignment in underrepresented population subgroups. This manuscript introduces several measures to account for geographic information in the assessment of cohort representation. METHODS: Metrics were defined across two themes: First, measures of recruitment, to assess if a study cohort is drawn at an expected rate and in an expected geographical pattern with respect to individuals in a reference cohort. Second, measures of individual characteristics, to assess if the individuals in the study cohort accurately reflect the sociodemographic, clinical, and geographic diversity observed across a reference cohort while accounting for the geospatial proximity of individuals. RESULTS: As an empirical demonstration, methods are applied to an active clinical study examining asthma in Black/African American patients at a US Midwestern pediatric hospital. Results illustrate how areas of over- and under-recruitment can be identified and contextualized in light of study recruitment patterns at an individual-level, highlighting the ability to identify a subset of features for which the study cohort closely resembled the broader population. In addition they provide an opportunity to dive deeper into misalignments, to identify study cohort members that are in some way distinct from the communities for which they are expected to represent. CONCLUSION: Together, these metrics provide a comprehensive spatial assessment of a study cohort with respect to a broader target population. Such an approach offers researchers a toolset by which to target expected generalization of results derived from a given study.

Metacognitive accuracy differences in Parkinson's disease and REM sleep behavioral disorder relative to healthy controls.

Background: Metacognition is the ability to monitor and self-assess cognitive performance. It can be impaired in neurodegenerative diseases, with implications for daily function, and the ability of patients to reliably report their symptoms to health professionals. However, metacognition has not been systematically assessed in early-mid stage Parkinson's disease (PD) and REM sleep behavioral disorder (RBD), a prodrome of PD. Objectives: This study aimed to evaluate metacognitive accuracy and self-confidence in PD and RBD patients across various cognitive tasks. Methods: We conducted detailed computerized cognitive assessments with 19 cognitive tasks within an established PD and RBD cohort. Participants self-rated their performance post-task. Metacognitive accuracy was calculated by comparing these ratings against objective performance and further analyzed against clinical and mental health factors. Results: PD and RBD patients' metacognitive accuracy aligned with control subjects. However, they exhibited lower confidence across cognitive domains, reflecting their reduced cognitive performance. A notable inverse correlation was observed between their confidence and MDS-UPDRS I and II scales and HADS anxiety and depression scores. Conclusion: Our findings indicate that patients with early to mid-stage PD and RBD are generally aware of their cognitive status, differing from other neurological disorders. The inverse relationship between patient confidence and symptoms of depression, anxiety, and daily life challenges underscores the impact of emotional and functional difficulties on their self-perception of cognitive abilities. This insight could be significant for understanding how these conditions affect mental health, aiding clinicians in developing more effective patient care strategies.

Shifting institutional culture to develop climate solutions with Open Science.

To address our climate emergency, "we must rapidly, radically reshape society"-Johnson & Wilkinson, All We Can Save. In science, reshaping requires formidable technical (cloud, coding, reproducibility) and cultural shifts (mindsets, hybrid collaboration, inclusion). We are a group of cross-government and academic scientists that are exploring better ways of working and not being too entrenched in our bureaucracies to do better science, support colleagues, and change the culture at our organizations. We share much-needed success stories and action for what we can all do to reshape science as part of the Open Science movement and 2023 Year of Open Science.

Clinical Practice Guidelines to Support Capacity Building in Orthopaedic Surgical Outreach: An International Consensus Building Approach.

BACKGROUND: Surgical outreach to low- and middle-income countries (LMICs) by organizations from high- income countries is on the rise to help address the growing burden of conditions warranting surgery. However, concerns remain about the impact and sustainability of such outreach. Leading organizations (e.g., the World Health Organization) advocate for a capacity-building approach to ensure the safety, quality, and sustainability of the local health-care system. Despite this, to our knowledge, no guidelines exist to inform such efforts. We aimed to develop clinical practice guidelines (CPGs) to support capacity-building in orthopaedic surgical outreach utilizing a multistakeholder and international voting panel. METHODS: We followed a modified American Academy of Orthopaedic Surgeons (AAOS) CPG development process. We systematically reviewed the existing literature across 7 predefined capacity-building domains (partnership, professional development, governance, community impact, finance, coordination, and culture). A writing panel composed of 6 orthopaedic surgeons with extensive experience in surgical outreach reviewed the existing literature and developed a consensus-based CPG for each domain. We created an international voting panel of orthopaedic surgeons and administrators who have leadership roles in outreach organizations or hospitals with which outreach organizations partner. Members individually reviewed the CPGs and voted to approve or disapprove each guideline. A CPG was considered approved if >80% of panel members voted to approve it. RESULTS: An international voting panel of 14 surgeons and administrators from 6 countries approved all 7 of the CPGs. Each CPG provides recommendations for capacity-building in a specific domain. For example, in the domain of partnership, the CPG recommends the development of a documented plan for ongoing, bidirectional partnership between the outreach organization and the local team. In the domain of professional development, the CPG recommends the development of a needs-based curriculum focused on both surgical and nonsurgical patient care utilizing didactic and hands-on techniques. CONCLUSIONS: As orthopaedic surgical outreach grows, best-practice CPGs to inform capacity-building initiatives can help to ensure that resources and efforts are optimized to support the sustainability of care delivery at local sites. These guidelines can be reviewed and updated in the future as evidence that supports capacity-building in LMICs evolves.The global burden of disease warranting surgery is substantial, and morbidity and mortality from otherwise treatable conditions remain disproportionately high in low- and middle-income countries (LMICs)1,2. It is estimated that up to 2 million (about 40%) of injury-related deaths in LMICs could be avoided annually if mortality rates were reduced to the level of those in high-income countries (HICs)3. Despite this, progress toward improved access to safe, timely surgery in resource-poor areas has been slow. Historically, nongovernmental organizations (NGOs) have tried to address unmet surgical needs through short-term outreach trips; however, growing criticism has highlighted the limitations of short-term trips, including limited follow-up, an increased burden on the local workforce, and further depletion of local resources4-6. In light of ongoing concerns, public health priorities have shifted toward models that emphasize long-term capacity-building rather than short-term care delivery. Capacity-building is an approach to health-care development that builds independence through infrastructure development, sustainability, and enhanced problem-solving while taking context into account7,8.

Online cognitive monitoring technology for people with Parkinson's disease and REM sleep behavioural disorder.

Automated online cognitive assessments are set to revolutionise clinical research and healthcare. However, their applicability for Parkinson's Disease (PD) and REM Sleep Behavioural Disorder (RBD), a strong PD precursor, is underexplored. Here, we developed an online battery to measure early cognitive changes in PD and RBD. Evaluating 19 candidate tasks showed significant global accuracy deficits in PD (0.65 SD, p = 0.003) and RBD (0.45 SD, p = 0.027), driven by memory, language, attention and executive underperformance, and global reaction time deficits in PD (0.61 SD, p = 0.001). We identified a brief 20-min battery that had sensitivity to deficits across these cognitive domains while being robust to the device used. This battery was more sensitive to early-stage and prodromal deficits than the supervised neuropsychological scales. It also diverged from those scales, capturing additional cognitive factors sensitive to PD and RBD. This technology offers an economical and scalable method for assessing these populations that can complement standard supervised practices.

Outcomes and complications of revision reverse shoulder arthroplasty after failed primary anatomic shoulder arthroplasty or hemiarthroplasty: a systematic review.

BACKGROUND: The purpose of this study is to systematically review the evidence in the literature to ascertain the functional outcomes, range of motion (ROM), and complication and reoperation rates after revision reverse shoulder arthroplasty (RSA) for a failed primary total shoulder arthroplasty (TSA) or hemiarthroplasty (HA). METHODS: Two independent reviewers performed the literature search based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the EMBASE, MEDLINE, and The Cochrane Library databases. Studies were included if they reported clinical outcomes for revision RSA for a failed primary TSA or HA. RESULTS: Our review found 23 studies including 1041 shoulders (627 TSA and 414 HA) meeting our inclusion criteria. The majority of patients were female (66.1%), with an average age of 69.0 years (range: 39-93 years) and a mean follow-up of 46.3 months. American Shoulder and Elbow Surgeons and visual analog scale pain scores improved from 32.6 to 61.9 and 6.7 to 2.7, respectively. ROM results include forward flexion, abduction, and external rotation, which improved from 59.4° to 107.7°, 50.7° to 104.4°, and 19.8° to 26.3°, respectively. Only 1 of the 10 studies reporting internal rotation found a statistically significant difference, with the mean internal rotation improving from S1-S3 preoperatively to L4-L5 postoperatively for patients undergoing HA. The overall complication rate and reoperation rate were 23.4% and 12.5%, respectively. The most common complications were glenoid component loosening (6.0%), fracture (periprosthetic, intraoperative, or other scapula fractures) (n = 4.7%), and infection (n = 3.3%). CONCLUSIONS: Revision RSA for a failed primary TSA and HA has been shown to result in excellent functional outcomes and improved ROM, suggesting that patients who have failed TSA or HA may benefit from a revision RSA.

Essential genes for Haemophilus parainfluenzae survival and biofilm growth.

Haemophilus parainfluenzae ( Hp ) is a Gram-negative, pleomorphic rod, highly prevalent and abundant as a commensal in the human oral cavity, and an infrequent extraoral opportunistic pathogen. Hp occupies multiple niches in the oral cavity, including the tongue dorsum, keratinized gingiva, and the supragingival plaque biofilm. As a member of the HACEK group, Hp is also known to cause infective endocarditis. Additionally, case reports have identified Hp as the causative agent of meningitis, septic arthritis, chronic osteomyelitis, septicemia, and a variety of other infectious diseases. Little is known about how Hp interacts with its neighbors in the healthy biofilm nor about its mechanisms of pathogenesis as an extraoral opportunistic pathogen. To address these unknowns, we identified the essential genomes of two Hp strains and the conditionally essential genes for their growth in in vitro biofilms aerobically and anaerobically. Using transposon insertion sequencing (TnSeq) with a highly saturated mariner transposon library in two strains, the ATCC33392 type-strain ( Hp 392) and a commensal oral isolate EL1 ( Hp EL1), we show that the essential genome of Hp 392 and Hp EL1 is composed of 395 and 384 genes, respectively. The core essential genome, consisting of 341 essential genes conserved between both strains, was composed of genes associated with genetic information processing, carbohydrate, protein, and energy metabolism. We also identified conditionally essential genes for aerobic and anaerobic biofilm growth, which were associated with carbohydrate and energy metabolism in both strains of Hp . Additionally, RNAseq analysis determined that most genes upregulated during anaerobic growth are not essential for Hp 392 anaerobic biofilm survival. The completion of this library and analysis under these conditions gives us a foundational insight into the basic biology of H. parainfluenzae in differing oxygen conditions, similar to its in vivo oral habitat. Further, the creation of this library presents a valuable tool for further investigation into conditionally essential genes for an organism that lives in close contact with many microbial species in the human oral habitat.

Spatial ecology of Haemophilus and Aggregatibacter in the human oral cavity.

Haemophilus and Aggregatibacter are two of the most common bacterial genera in the human oral cavity, encompassing both commensals and pathogens of substantial ecological and medical significance. In this study, we conducted a metapangenomic analysis of oral Haemophilus and Aggregatibacter species to uncover genomic diversity, phylogenetic relationships, and habitat specialization within the human oral cavity. Using three metrics-pangenomic gene content, phylogenomics, and average nucleotide identity (ANI)-we first identified distinct species and sub-species groups among these genera. Mapping of metagenomic reads then revealed clear patterns of habitat specialization, such as Aggregatibacter species predominantly in dental plaque, a distinctive Haemophilus parainfluenzae sub-species group on the tongue dorsum, and H. sp. HMT-036 predominantly in keratinized gingiva and buccal mucosa. In addition, we found that supragingival plaque samples contained predominantly only one out of the three taxa, H. parainfluenzae, Aggregatibacter aphrophilus, and A. sp. HMT-458, suggesting independent niches or a competitive relationship. Functional analyses revealed the presence of key metabolic genes, such as oxaloacetate decarboxylase, correlated with habitat specialization, suggesting metabolic versatility as a driving force. Additionally, heme synthesis distinguishes H. sp. HMT-036 from closely related Haemophilus haemolyticus, suggesting that the availability of micronutrients, particularly iron, was important in the evolutionary ecology of these species. Overall, our study exemplifies the power of metapangenomics to identify factors that may affect ecological interactions within microbial communities, including genomic diversity, habitat specialization, and metabolic versatility. IMPORTANCE: Understanding the microbial ecology of the mouth is essential for comprehending human physiology. This study employs metapangenomics to reveal that various Haemophilus and Aggregatibacter species exhibit distinct ecological preferences within the oral cavity of healthy individuals, thereby supporting the site-specialist hypothesis. Additionally, it was observed that the gene pool of different Haemophilus species correlates with their ecological niches. These findings shed light on the significance of key metabolic functions in shaping microbial distribution patterns and interspecies interactions in the oral ecosystem.

A patient journey audit tool (PJAT) to assess quality indicators in a nuclear medicine service.

PURPOSE: To develop a nuclear medicine specific patient journey audit tool (PJAT) to survey and audit patient journeys in a nuclear medicine department such as staff interaction with patients, equipment, quality of imaging and laboratory procedures, patient protection, infection control and radiation safety, with a view to optimising patient care and providing a high-quality nuclear medicine service. METHODS: The PJAT was developed specifically for use in nuclear medicine practices. Thirty-two questions were formulated in the PJAT to test the department's compliance to the Australian National Safety and Quality Health Service Standards, namely clinical governance, partnering with consumers, preventing and controlling health care infection, medication safety, comprehensive care, communicating for safety, blood management and recognising and responding to acute deterioration. The PJAT was also designed to test our department's adherence to diagnostic reference levels (DRL). A total of 60 patient journey audits were completed for patients presenting for nuclear medicine, positron emission tomography and bone mineral density procedures during a consecutive 4-week period to audit the range of procedures performed. A further 120 audits were captured for common procedures in nuclear medicine and positron emission tomography during the same period. Thus, a total of 180 audits were completed. A subset of 12 patients who presented for blood labelling procedures were audited to solely assess the blood management standard. RESULTS: The audits demonstrated over 85% compliance for the Australian national health standards. One hundred percent compliance was noted for critical aspects such as correct patient identification for the correct procedure prior to radiopharmaceutical administration, adherence to prescribed dose limits and distribution of the report within 24 h of completion of the imaging procedure. CONCLUSION: This PJAT can be applied in nuclear medicine departments to enhance quality programmes and patient care. Austin Health has collaborated with the IAEA to formulate the IAEA PJAT, which is now available globally for nuclear medicine departments to survey patient journeys.

Prodromal dementia with Lewy bodies in REM sleep behavior disorder: A multicenter study.

INTRODUCTION: Isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) is a powerful early predictor of dementia with Lewy bodies (DLB) and Parkinson's disease (PD). This provides an opportunity to directly observe the evolution of prodromal DLB and to identify which cognitive variables are the strongest predictors of evolving dementia. METHODS: IRBD participants (n = 754) from 10 centers of the International RBD Study Group underwent annual neuropsychological assessment. Competing risk regression analysis determined optimal predictors of dementia. Linear mixed-effect models determined the annual progression of neuropsychological testing. RESULTS: Reduced attention and executive function, particularly performance on the Trail Making Test Part B, were the strongest identifiers of early DLB. In phenoconverters, the onset of cognitive decline began up to 10 years prior to phenoconversion. Changes in verbal memory best differentiated between DLB and PD subtypes. DISCUSSION: In iRBD, attention and executive dysfunction strongly predict dementia and begin declining several years prior to phenoconversion. HIGHLIGHTS: Cognitive decline in iRBD begins up to 10 years prior to phenoconversion. Attention and executive dysfunction are the strongest predictors of dementia in iRBD. Decline in episodic memory best distinguished dementia-first from parkinsonism-first phenoconversion.

The oral microbiome: diversity, biogeography and human health.

The human oral microbiota is highly diverse and has a complex ecology, comprising bacteria, microeukaryotes, archaea and viruses. These communities have elaborate and highly structured biogeography that shapes metabolic exchange on a local scale and results from the diverse microenvironments present in the oral cavity. The oral microbiota also interfaces with the immune system of the human host and has an important role in not only the health of the oral cavity but also systemic health. In this Review, we highlight recent advances including novel insights into the biogeography of several oral niches at the species level, as well as the ecological role of candidate phyla radiation bacteria and non-bacterial members of the oral microbiome. In addition, we summarize the relationship between the oral microbiota and the pathology of oral diseases and systemic diseases. Together, these advances move the field towards a more holistic understanding of the oral microbiota and its role in health, which in turn opens the door to the study of novel preventive and therapeutic strategies.

Contextual Determinants of Time to Surgery for Patients With Hip Fracture.

Importance: Surgery within 24 hours after a hip fracture improves patient morbidity and mortality, which has led some hospitals to launch quality improvement programs (eg, targeted resource management, documented protocols) to address delays. However, these programs have had mixed results in terms of decreased time to surgery (TTS), identifying an opportunity to improve the effectiveness of interventions. Objective: To identify the contextual determinants (site-specific barriers and facilitators) of TTS for patients with hip fracture across diverse hospitals. Design, Setting, and Participants: This qualitative mixed-methods study used an exploratory sequential design that comprised 2 phases. In phase 1, qualitative semistructured interviews were conducted with stakeholders involved in hip fracture care (orthopedic surgeons or residents, emergency medicine physicians, hospitalists, anesthesiologists, nurses, and clinical or support staff) at 4 hospitals with differing financial, operational, and educational structures. Interviews were completed between May and July 2021. In phase 2, a quantitative survey assessing contextual determinants of TTS within 24 hours for adult patients with hip fracture was completed by orthopedic surgeon leaders representing 23 diverse hospitals across the US between May and July 2022. Data analysis was performed in August 2022. Main Outcomes and Measures: Thematic analysis of the interviews identified themes of contextual determinants of TTS within 24 hours for patients with hip fracture. The emergent contextual determinants were then measured across multiple hospitals, and frequency and distribution were used to assess associations between determinants and various hospital characteristics (eg, setting, number of beds). Results: A total of 34 stakeholders were interviewed in phase 1, and 23 surveys were completed in phase 2. More than half of respondents in both phases were men (19 [56%] and 18 [78%], respectively). The following 4 themes of contextual determinants of TTS within 24 hours were identified: availability, care coordination, improvement climate, and incentive structure. Within these themes, the most commonly identified determinants across the various hospitals involved operating room availability, a formal comanagement system between orthopedics and medicine or geriatrics, the presence of a physician champion focused on timely surgery, and a program that facilitates improvement work. Conclusions and Relevance: In this study, contextual determinants of TTS within 24 hours for patients with hip fracture varied across hospital sites and could not be generalized across various hospital contexts because no 2 sites had identical profiles. As such, these findings suggest that guidance on strategies for improving TTS should be based on the contextual determinants unique to each hospital.

Subscapularis repair for reverse shoulder arthroplasty: a systematic review and meta-analysis.

BACKGROUND: The purpose of this study is to perform a systematic review of the literature evaluating the importance of subscapularis repair in patients who underwent reverse shoulder arthroplasty (RSA). METHODS: A systematic search of articles in PubMed, EMBASE, and the Cochrane Library databases was carried out according to the PRISMA guidelines. Cohort studies comparing RSA with subscapularis repair vs. RSA without subscapularis repair were included. All statistical analysis was performed using Review Manager. A P value of <.05 was considered to be statistically significant. RESULTS: Seventeen studies with 2620 patients were included. Subscapularis repair resulted in less instability compared to without subscapularis repair (0.8% vs. 4.2%, P = .04), and there were no significant differences in rate of instability with lateralization (0.6% vs. 1.6%, P = .40), revision rates (2.6% vs. 3.9%, P = .62), and complication rates (7.7% vs. 4.9%, P = .21). Subscapularis repair had improved American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores (83.6 vs. 80.2, P = .02) and Constant scores (72.6 vs. 68.9, P < .01) but there was not a significant difference in visual analog scale pain scores (1.2 vs. 1.6, P = .11). Subscapularis repair had a significant difference in forward flexion (140° vs. 137°, P = .04) and internal rotation score (5.5 vs. 4.6, P = .001); however, there was no significant difference in external rotation (35° vs. 35°, P = .80) and abduction (117° vs. 123°, P = .13). CONCLUSION: This study found that RSA with subscapularis repair demonstrated a reduction in the occurrence of implant instability with medialized implants. However, subscapularis repair did not yield improvements in revision rates, complications, or instability with lateralized implants. Additionally, other outcome measures such as ASES, Constant score, and range of motion exhibited statistically significant improvements with subscapularis repair but did not surpass clinically significant thresholds.

Phages are unrecognized players in the ecology of the oral pathogen Porphyromonas gingivalis.

BACKGROUND: Porphyromonas gingivalis (hereafter "Pg") is an oral pathogen that has been hypothesized to act as a keystone driver of inflammation and periodontal disease. Although Pg is most readily recovered from individuals with actively progressing periodontal disease, healthy individuals and those with stable non-progressing disease are also colonized by Pg. Insights into the factors shaping the striking strain-level variation in Pg, and its variable associations with disease, are needed to achieve a more mechanistic understanding of periodontal disease and its progression. One of the key forces often shaping strain-level diversity in microbial communities is infection of bacteria by their viral (phage) predators and symbionts. Surprisingly, although Pg has been the subject of study for over 40 years, essentially nothing is known of its phages, and the prevailing paradigm is that phages are not important in the ecology of Pg. RESULTS: Here we systematically addressed the question of whether Pg are infected by phages-and we found that they are. We found that prophages are common in Pg, they are genomically diverse, and they encode genes that have the potential to alter Pg physiology and interactions. We found that phages represent unrecognized targets of the prevalent CRISPR-Cas defense systems in Pg, and that Pg strains encode numerous additional mechanistically diverse candidate anti-phage defense systems. We also found that phages and candidate anti-phage defense system elements together are major contributors to strain-level diversity and the species pangenome of this oral pathogen. Finally, we demonstrate that prophages harbored by a model Pg strain are active in culture, producing extracellular viral particles in broth cultures. CONCLUSION: This work definitively establishes that phages are a major unrecognized force shaping the ecology and intra-species strain-level diversity of the well-studied oral pathogen Pg. The foundational phage sequence datasets and model systems that we establish here add to the rich context of all that is already known about Pg, and point to numerous avenues of future inquiry that promise to shed new light on fundamental features of phage impacts on human health and disease broadly. Video Abstract.

Capacity Assessment Tool to Promote Capacity Building in Global Orthopaedic Surgical Outreach.

BACKGROUND: A growing number of nongovernmental organizations from high-income countries aim to provide surgical outreach for patients in low- and middle-income countries in a manner that builds capacity. There remains, however, a paucity of measurable steps to benchmark and evaluate capacity-building efforts. Based on a framework for capacity building, the present study aimed to develop a Capacity Assessment Tool for orthopaedic surgery (CAT-os) that could be utilized to evaluate and promote capacity building. METHODS: To develop the CAT-os tool, we utilized methodological triangulation-an approach that incorporates multiple different types of data. We utilized (1) the results of a systematic review of capacity-building best practices in surgical outreach, (2) the HEALTHQUAL National Organizational Assessment Tool, and (3) 20 semistructured interviews to develop a draft of the CAT-os. We subsequently iteratively used a modified nominal group technique with a consortium of 8 globally experienced surgeons to build consensus, which was followed by validation through member-checking. RESULTS: The CAT-os was developed and validated as a formal instrument with actionable steps in each of 7 domains of capacity building. Each domain includes items that are scaled for scoring. For example, in the domain of partnership, items range from no formalized plans for sustainable, bidirectional relationships (no capacity) to local surgeons and other health-care workers independently participating in annual meetings of surgical professional societies and independently creating partnership with third party organizations (optimal capacity). CONCLUSIONS: The CAT-os details steps to assess capacity of a local facility, guide capacity-improvement efforts during surgical outreach, and measure the impact of capacity-building efforts. Capacity building is a frequently cited and commendable approach to surgical outreach, and this tool provides objective measurement to aid in improving the capacity in low and middle-income countries through surgical outreach.

Site-specialization of human oral Gemella species.

Gemella species are core members of the human oral microbiome in healthy subjects and are regarded as commensals, although they can cause opportunistic infections. Our objective was to evaluate the site-specialization of Gemella species among various habitats within the mouth by combining pangenomics and metagenomics. With pangenomics, we identified genome relationships and categorized genes as core and accessory to each species. With metagenomics, we identified the primary oral habitat of individual genomes. Our results establish that the genomes of three species, G. haemolysans, G. sanguinis and G. morbillorum, are abundant and prevalent in human mouths at different oral sites: G. haemolysans on buccal mucosa and keratinized gingiva; G. sanguinis on tongue dorsum, throat, and tonsils; and G. morbillorum in dental plaque. The gene-level basis of site-specificity was investigated by identifying genes that were core to Gemella genomes at a specific oral site but absent from other Gemella genomes. The riboflavin biosynthesis pathway was present in G. haemolysans genomes associated with buccal mucosa but absent from the rest of the genomes. Overall, metapangenomics show that Gemella species have clear ecological preferences in the oral cavity of healthy humans and provides an approach to identifying gene-level drivers of site specificity.

The Use and Downstream Associations of Magnetic Resonance Imaging for Lateral Epicondylitis.

PURPOSE: Low-value imaging is associated with wasteful health care spending and patient harm. The routine use of magnetic resonance imaging (MRI) for the work-up of lateral epicondylitis is an example of low-value imaging. As such, our aim was to investigate the use of MRIs ordered for lateral epicondylitis, the characteristics of those undergoing an MRI, and the downstream associations of MRI with other care. METHODS: We identified patients aged ≥18 years with a diagnosis of lateral epicondylitis between 2010 and 2019 using a Humana claims database. We identified patients with a Current Procedural Terminology code corresponding to an elbow MRI. We analyzed the use and downstream treatment cascades in those undergoing MRI. Multivariable logistic regression models were used to assess the odds of undergoing an MRI, adjusting for age, sex, insurance type, and comorbidity index. Separate multivariable logistic regression analyses were used to determine the association between undergoing an MRI and the incidence of secondary outcomes (eg, receiving surgery). RESULTS: A total of 624,102 patients met the inclusion criteria. Of 8,209 (1.3%) patients undergoing MRI, 3,584 (44%) underwent it within 90 days after diagnosis. There was notable regional variation in MRI use. The MRIs were ordered most frequently by primary care specialties and for younger, female, commercially insured, and patients with more comorbidities. Performance of an MRI was associated with an increase in downstream treatments, including surgery (odds ratio [OR], 9.58 [9.12-10.07]), injection (OR, 2.90 [2.77-3.04]), therapy (OR, 1.81 [1.72-1.91]), and cost ($134 per patient). CONCLUSIONS: Although there is variation in the use of MRI for lateral epicondylitis and its use is associated with downstream effects, the routine use of MRI for the diagnosis of lateral epicondylitis is low. CLINICAL RELEVANCE: The routine use of MRI for lateral epicondylitis is low. Understanding interventions to minimize such low-value care in lateral epicondylitis can be used to inform improvement efforts to minimize low-value care for other conditions.

Mucin glycans drive oral microbial community composition and function.

Human microbiome composition is closely tied to health, but how the host manages its microbial inhabitants remains unclear. One important, but understudied, factor is the natural host environment: mucus, which contains gel-forming glycoproteins (mucins) that display hundreds of glycan structures with potential regulatory function. Leveraging a tractable culture-based system to study how mucins influence oral microbial communities, we found that mucin glycans enable the coexistence of diverse microbes, while resisting disease-associated compositional shifts. Mucins from tissues with unique glycosylation differentially tuned microbial composition, as did isolated mucin glycan libraries, uncovering the importance of specific glycan patterns in microbiome modulation. We found that mucins shape microbial communities in several ways: serving as nutrients to support metabolic diversity, organizing spatial structure through reduced aggregation, and possibly limiting antagonism between competing taxa. Overall, this work identifies mucin glycans as a natural host mechanism and potential therapeutic intervention to maintain healthy microbial communities.

Site Specialization of Human Oral Veillonella Species.

Veillonella species are abundant members of the human oral microbiome with multiple interspecies commensal relationships. Examining the distribution patterns of Veillonella species across the oral cavity is fundamental to understanding their oral ecology. In this study, we used a combination of pangenomic analysis and oral metagenomic information to clarify Veillonella taxonomy and to test the site specialist hypothesis for the Veillonella genus, which contends that most oral bacterial species are adapted to live at specific oral sites. Using isolate genome sequences combined with shotgun metagenomic sequence data, we showed that Veillonella species have clear, differential site specificity: Veillonella parvula showed strong preference for supra- and subgingival plaque, while closely related V. dispar, as well as more distantly related V. atypica, preferred the tongue dorsum, tonsils, throat, and hard palate. In addition, the provisionally named Veillonella sp. Human Microbial Taxon 780 showed strong site specificity for keratinized gingiva. Using comparative genomic analysis, we identified genes associated with thiamine biosynthesis and the reductive pentose phosphate cycle that may enable Veillonella species to occupy their respective habitats. IMPORTANCE Understanding the microbial ecology of the mouth is fundamental for understanding human physiology. In this study, metapangenomics demonstrated that different Veillonella species have clear ecological preferences in the oral cavity of healthy humans, validating the site specialist hypothesis. Furthermore, the gene pool of different Veillonella species was found to be reflective of their ecology, illuminating the potential role of vitamins and carbohydrates in determining Veillonella distribution patterns and interspecies interactions.