Detecting Risky Authentication Using the OpenID Connect Token Exchange Time.

With the rise in sophisticated cyber threats, traditional authentication methods are no longer sufficient. Risk-based authentication (RBA) plays a critical role in the context of the zero trust framework-a paradigm shift that assumes no trust within or outside the network. This research introduces a novel proposal as its core: utilization of the time required by OpenID Connect (OIDC) token exchanges as a new RBA feature. This innovative approach enables the detection of tunneled connections without any intervention from the user's browser or device. By analyzing the duration of OIDC token exchanges, the system can identify any irregularities that may signify unauthorized access attempts. This approach not only improves upon existing RBA frameworks but is also in alignment with the broader movement toward intelligent and responsive security systems.

Bonobos Maintain Immune System Diversity with Three Functional Types of MHC-B.

Fast-evolving MHC class I polymorphism serves to diversify NK cell and CD8 T cell responses in individuals, families, and populations. Because only chimpanzee and bonobo have strict orthologs of all HLA class I, their study gives unique perspectives on the human condition. We defined polymorphism of Papa-B, the bonobo ortholog of HLA-B, for six wild bonobo populations. Sequences for Papa-B exon 2 and 3 were determined from the genomic DNA in 255 fecal samples, minimally representing 110 individuals. Twenty-two Papa-B alleles were defined, each encoding a different Papa-B protein. No Papa-B is identical to any chimpanzee Patr-B, human HLA-B, or gorilla Gogo-B. Phylogenetic analysis identified a clade of MHC-B, defined by residues 45-74 of the α1 domain, which is broadly conserved among bonobo, chimpanzee, and gorilla. Bonobo populations have 3-14 Papa-B allotypes. Three Papa-B are in all populations, and they are each of a different functional type: allotypes having the Bw4 epitope recognized by killer cell Ig-like receptors of NK cells, allotypes having the C1 epitope also recognized by killer cell Ig-like receptors, and allotypes having neither epitope. For population Malebo, these three Papa-B are the only Papa-B allotypes. Although small in number, their sequence divergence is such that the nucleotide diversity (mean proportional distance) of Papa-B in Malebo is greater than in the other populations and is also greater than expected for random combinations of three Papa-B Overall, Papa-B has substantially less diversity than Patr-B in chimpanzee subspecies and HLA-B in indigenous human populations, consistent with bonobo having experienced narrower population bottlenecks.

IL-33 promotes food anaphylaxis in epicutaneously sensitized mice by targeting mast cells.

BACKGROUND: Cutaneous exposure to food allergens predisposes to food allergy, which is commonly associated with atopic dermatitis (AD). Levels of the epithelial cytokine IL-33 are increased in skin lesions and serum of patients with AD. Mast cells (MCs) play a critical role in food-induced anaphylaxis and express the IL-33 receptor ST2. The role of IL-33 in patients with MC-dependent food anaphylaxis is unknown. OBJECTIVE: We sought to determine the role and mechanism of action of IL-33 in patients with food-induced anaphylaxis in a model of IgE-dependent food anaphylaxis elicited by oral challenge of epicutaneously sensitized mice. METHODS: Wild-type, ST2-deficient, and MC-deficient KitW-sh/W-sh mice were epicutaneously sensitized with ovalbumin (OVA) and then challenged orally with OVA. Body temperature was measured by means of telemetry, Il33 mRNA by means of quantitative PCR, and IL-33, OVA-specific IgE, and mouse mast cell protease 1 by means of ELISA. Bone marrow-derived mast cell (BMMC) degranulation was assessed by using flow cytometry. RESULTS: Il33 mRNA expression was upregulated in tape-stripped mouse skin and scratched human skin. Tape stripping caused local and systemic IL-33 release in mice. ST2 deficiency, as well as ST2 blockade before oral challenge, significantly reduced the severity of oral anaphylaxis without affecting the systemic TH2 response to the allergen. Oral anaphylaxis was abrogated in KitW-sh/W-sh mice and restored by means of reconstitution with wild-type but not ST2-deficient BMMCs. IL-33 significantly enhanced IgE-mediated degranulation of BMMCs in vitro. CONCLUSION: IL-33 is released after mechanical skin injury, enhances IgE-mediated MC degranulation, and promotes oral anaphylaxis after epicutaneous sensitization by targeting MCs. IL-33 neutralization might be useful in treating food-induced anaphylaxis in patients with AD.

Readability of patient education materials on the American Orthopaedic Society for Sports Medicine website.

BACKGROUND: The recommended readability of patient education materials by the American Medical Association (AMA) and National Institutes of Health (NIH) should be no greater than a sixth-grade reading level. However, online resources may be too complex for some patients to understand, and poor health literacy predicts inferior health-related quality of life outcomes. AIM: This study evaluated whether the American Orthopaedic Society for Sports Medicine (AOSSM) website's patient education materials meet recommended readability guidelines for medical information. We hypothesized that the readability of these online materials would have a Flesch-Kincaid formula grade above the sixth grade. METHODS: All 65 patient education entries of the AOSSM website were analyzed for grade level readability using the Flesch-Kincaid formula, a widely used and validated tool to evaluate the text reading level. RESULTS: The average (standard deviation) readability of all 65 articles was grade level 10.03 (1.44); 64 articles had a readability score above the sixth-grade level, which is the maximum level recommended by the AMA and NIH. Mean readability of the articles exceeded this level by 4.03 grade levels (95% CI, 3.7-4.4; P < 0.0001). We found post-hoc that only 7 articles had a readability score ≤ an eighth-grade level, the average reading level of US adults. Mean readability of the articles exceeded this level by 2.03 grade levels (95% CI, 1.7-2.4; P < 0.0001). CONCLUSION: The readability of online AOSSM patient education materials exceeds the readability level recommended by the AMA and NIH, and is above the average reading level of the majority of US adults. This online information may be of limited utility to most patients due to a lack of comprehension. Our study provides a clear example of the need to improve the readability of specific education material in order to maximize the efficacy of multimedia sources.

Social media and postsecondary student adoption of mental health labels: protocol for a scoping review.

INTRODUCTION: Many postsecondary students use social media at an age when mental health issues often arise for the first time. On social media, students describe their mental states or social interactions using psychiatric language. This is a process of mental health labelling as opposed to receiving a formal diagnosis from a psychiatrist. Despite substantial literature on psychiatric labelling effects such as stigma, little research has addressed the mechanisms and effects of labelling through social media. Our objective is to summarise the existing evidence to address this gap. METHODS AND ANALYSIS: This review includes articles in English published since 1995 on how postsecondary students interact with mental health labels in their use of social media. We will consider empirical studies and theses. The search strategy includes SCOPUS, PubMed, OVID MEDLINE (to access APA PsycINFO), Web of Science and ProQuest Global Dissertations and Theses. This scoping review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extensions for protocols and Scoping Reviews guidelines. The artificial intelligence application, Connected Papers, will assist in identifying additional references. The outcomes of interest are labelling by self or others and changes in self-concept and presentation associated with these labels. Two researchers will independently identify the included studies and extract data, solving disagreements with a third opinion. We will produce tables and narrative descriptions of the operationalisation and measurement methods of labelling and social media use, reported effects and uses of labelling, and explanatory mechanisms for the adoption of labels. ETHICS AND DISSEMINATION: This literature review does not require ethics approval. The researchers will present their findings for publication in an open-access peer-reviewed journal and at student/scientific conferences. Potential knowledge users include university students, social media users, researchers, mental health professionals and on-campus mental health services.

Nature of quantum states created by one photon absorption: pulsed coherent vs pulsed incoherent light.

We analyze electronically excited nuclear wave functions and their coherence when subjecting a molecule to the action of natural, pulsed incoherent solar-like light and to that of ultrashort coherent light assumed to have the same center frequencies and spectral bandwidths. Specifically, we compute the spatiotemporal dependence of the excited wave packets and their electronic coherence for these two types of light sources, on different electronic potential energy surfaces. The resultant excited state wave functions are shown to be dramatically different, reflecting the light source from which they originated. In addition, electronic coherence is found to decay significantly faster for incoherent light than for coherent ultrafast excitation, for both continuum and bound wave packets. These results confirm that the dynamics observed from ultrashort coherent excitation does not reflect what happens in processes induced by solar-like radiation, and conclusions drawn from one do not, in general, apply to the other. These results provide further support to the view that the dynamics observed in studies using ultrashort coherent pulses can be significantly different than those that would result from excitation with natural incoherent light.

Systematic Comparison of Ligament Reconstruction With Tendon Interposition and Suture-Button Suspensionplasty for Trapeziometacarpal Osteoarthritis.

Ligament reconstruction tendon interposition (LRTI) and suture-button suspensionplasty (SBS) are both common treatment options for trapeziometacarpal osteoarthritis. The primary purpose of this systematic review was to compare the subjective improvement in patient-reported outcomes in regard to disability for patients undergoing LRTI and SBS for trapeziometacarpal osteoarthritis. A secondary purpose was to compare the subjective improvement, objective outcome scores, and complication rates following both procedures. We performed a systematic review using PubMed, Scopus, and Embase to compare the clinical outcomes of LRTI and SBS. Inclusion criteria were level I-IV evidence articles reporting postoperative Disabilities of the Arm, Shoulder, and Hand (DASH) or QuickDASH scores. Study methodological quality, risk of bias, and recommendation strength were assessed. This systematic review included 31 studies for final analysis with 1289 thumbs undergoing LRTI (25 studies) and 113 thumbs undergoing SBS (6 studies). Both procedures demonstrated similar improvement in DASH and/or QuickDASH scores, while key pinch and grip strength inconsistently improved following both procedures. Complication rate was similar between the 2 procedures; LRTI 12% and SBS 13%. Although both LRTI and SBS seem to provide improved short-term patient-reported functional improvement and objective strength, there was significant heterogeneity within the included studies, and those studies discussing SBS were of lower quality evidence than those of LRTI. Thus, to truly delineate whether a difference exists between these 2 techniques for the treatment of first carpometacarpal joint arthritis, larger prospectively designed studies of high-quality evidence are necessary.

Delayed administration of a small molecule tropomyosin-related kinase B ligand promotes recovery after hypoxic-ischemic stroke.

BACKGROUND AND PURPOSE: Stroke is the leading cause of long-term disability in the United States, yet no drugs are available that are proven to improve recovery. Brain-derived neurotrophic factor stimulates neurogenesis and plasticity, processes that are implicated in stroke recovery. It binds to both the tropomyosin-related kinase B and p75 neurotrophin receptors. However, brain-derived neurotrophic factor is not a feasible therapeutic agent, and no small molecule exists that can reproduce its binding to both receptors. We tested the hypothesis that a small molecule (LM22A-4) that selectively targets tropomyosin-related kinase B would promote neurogenesis and functional recovery after stroke. METHODS: Four-month-old mice were trained on motor tasks before stroke. After stroke, functional test results were used to randomize mice into 2 equally, and severely, impaired groups. Beginning 3 days after stroke, mice received LM22A-4 or saline vehicle daily for 10 weeks. RESULTS: LM22A-4 treatment significantly improved limb swing speed and accelerated the return to normal gait accuracy after stroke. LM22A-4 treatment also doubled both the number of new mature neurons and immature neurons adjacent to the stroke. Drug-induced differences were not observed in angiogenesis, dendritic arborization, axonal sprouting, glial scar formation, or neuroinflammation. CONCLUSIONS: A small molecule agonist of tropomyosin-related kinase B improves functional recovery from stroke and increases neurogenesis when administered beginning 3 days after stroke. These findings provide proof-of-concept that targeting of tropomyosin-related kinase B alone is capable of promoting one or more mechanisms relevant to stroke recovery. LM22A-4 or its derivatives might therefore serve as "pro-recovery" therapeutic agents for stroke.

Linear response in the strong field domain.

We show that, while it is well-known that first-order perturbation theory leads to linear response (of, e.g., a material system to an external field), the reverse is not true: linear response does not necessarily imply the validity of first-order perturbation theory, nor does it follow from it that the external perturbation is weak. We do so by analyzing the intensity dependence in the photoexcitation followed by dissociation or isomerization of a bound molecular system by a shaped broadband laser pulse. We show that, in certain cases where strong field effects are definitely present, the observed photoexcitation yield as a function of intensity may exhibit linear dependence over a wide range of intensities. The behavior is shown to coexist with a rather extensive range of coherent control over the branching ratios, an effect that was shown in the past to be impossible in the single precursor state (e.g., in the first-order perturbation theory) domain. For example, we demonstrate computationally that when (flat continuum-mediated) Raman transitions are present, appropriate pulse shaping can lead to a linear yield with intensity over a wide range of intensities, while coherent control over the branching ratio is significant. Thus, it is not necessary to invoke external bath effects (as is currently being done) to explain present-day experiments where coherent control is observed in the linear response regime.

Comprehensive analysis of trends in Medicare utilization and reimbursement in Physical Medicine & Rehabilitation: 2012 to 2017.

INTRODUCTION: There is an absence of literature describing Medicare utilization by physiatrists, despite their key role in treating Medicare enrollees with qualifying disabilities and common neuromusculoskeletal conditions. OBJECTIVE: To analyze Medicare data regarding physiatrists and their beneficiaries, services, and reimbursement, as well as trends in utilization and geographic distribution. DESIGN AND SETTING: Retrospective analysis of publicly available Centers for Medicare & Medicaid Services data for Medicare beneficiaries receiving physiatric services from 2012 to 2017. MAIN OUTCOME MEASURES: After adjustment for inflation, variables assessed for changes over time included provider and beneficiary demographics, total Medicare reimbursement, and the number of services provided, subsequently separated by drug and medical service metrics. Lorenz curves and Gini coefficients were computed to study reimbursement inequality. Choropleth maps were generated to assess geographic differences in physician density and reimbursement, both by state and ZIP code. RESULTS: The number of physiatrists utilizing Medicare increased from 7230 to 7895 from 2012 to 2017, whereas the average number of unique beneficiaries per clinician remained constant (307 vs. 310; p = .51). The beneficiaries' mean hierarchical conditions category (HCC) health risk score, normalized to 1.0 for the average beneficiary, increased significantly from 2012 to 2017 (1.72 vs. 1.80; p < .01). The mean Medicare reimbursement per physiatrist decreased significantly from 2012 to 2017 ($131,960 vs. $117,623; p < .001), whereas the mean number of services remained constant (3243 vs. 3077; p = .132). Botulinum toxin and baclofen injections were the two most reimbursed drug-related services. Gini coefficients ranged from 0.52 to 0.53 for 2012 to 2017, suggesting moderate reimbursement inequality, with the 75th percentile receiving on average two times the median. Both physician density and top earners were concentrated in urban and metropolitan areas. CONCLUSIONS: Despite rising health care costs and the increasing medical complexity of physiatrists' beneficiaries, Medicare payments have decreased over time. These trends are relevant to both providers and policymakers, particularly in light of unequal geographic distribution of physiatrists across the country.

Effects of COVID-19 on Geographical Trends in the Orthopaedic Surgery Residency Match.

Historically, medical students often match within the same geographic location or to an orthopaedic surgery residency program affiliated with their medical school. The objective of this investigation was to determine differences in geographic trends between orthopaedic residents matching before and during the Coronavirus-19 (COVID-19) pandemic. METHODS: This study analyzed 2 groups of orthopaedic residents: Pre-COVID cohort (years 2016-2020) and COVID-impacted cohort (year 2021). A list of accredited orthopaedic surgery residency programs (n = 202) was obtained. Orthopaedic residency program webpages were located (region [n = 4], division [n = 9], state [n = 50]). For each resident, their medical school and year of postgraduate training were recorded. Year 2021 resident information was obtained from the orthopaedic residency program webpages, social media accounts, and medical school match lists. Residency programs affiliated with a medical school were also assigned. Descriptive statistics were performed. Two sample Student t tests with Bonferroni correction applied to p-values (α < 0.05 significant) were performed. RESULTS: There were 4,832 residents analyzed (4,074 in Pre-COVID cohort; 758 in COVID-impacted cohort [758/868 of all positions in 2021 Match]). Statistically significant differences were detected between the COVID-impacted cohort (39.6%, p < 0.001) matching in the same state as their medical school (Pre-COVID 33.1%) and the COVID-impacted cohort (28.0%, p < 0.001) matching to a residency program affiliated with their medical school (Pre-COVID 21.2%). In the COVID-impacted cohort, students who matched in state matched to their home program more frequently (69.3%) compared with the Pre-COVID cohort (60.5%). Geographically, there was a difference in the COVID-impacted cohort (52.5%, p < 0.011) matching in the same division (Pre-COVID 47.5%). No statistically significant differences were identified for residents matching to the same region as their medical school (Pre-COVID 60.1%; COVID-impacted 61%, p = 0.968). CONCLUSION: Residents matching in the same state, in the same division, and to a residency program affiliated with their medical school increased significantly in the COVID-impacted cohort. There was no difference between cohorts matching in the same region as their medical school. Level of Evidence: Observational/Cross-Sectional.

[Corrigendum] The cranberry flavonoids PAC DP­9 and quercetin aglycone induce cytotoxicity and cell cycle arrest and increase cisplatin sensitivity in ovarian cancer cells.

Following the publication of this article, an interested reader drew to the author's attention that, in Fig. 5D on p. 1931, the two rightmost panels appeared to have been inverted for the SKOV3 cell line (i.e., the 'Q­aglycone' and 'PAC DP­9' data panels appeared to have been included in this figure the wrong way around). The authors checked the figure, and realized that these panels had indeed erroneously been inverted during the assembly of the figure. The corrected version of Fig. 5 is shown on the next page. The authors regret that this error was not picked up upon before the paper was sent to press, and thank the Editor of International Journal of Oncology for allowing them the opportunity to publish this corrigendum. Furthermore, they regret any inconvenience caused to the readership. [International Journal of Oncology 46: 1924­1934, 2015; DOI: 10.3892/ijo.2015.2931].

On-site Clinical Care for Professional Dance Companies.

Thirty years ago the introduction of on-site health care for professional dance companies was a novel concept and dance medicine clinicians often had limited on-site hours, restricted treatment space, and small budgets. Companies are now developing fully staffed on-site clinics and backstage care that provide a multidisciplinary approach to dancer health and wellness. On-site dance medicine programs focus on holistic dancer health and preventive care rather than just triage and rehabilitation. Best practice recommendations for care of professional dancer patients allow for streamlined patient care within a network of medical professionals who understand the demands of a professional dance career.

Percutaneous Needle Fasciotomy versus Collagenase Injection for Dupuytren's Contracture: A Systematic Review of Comparative Studies.

Introduction The purpose of this study was to review and compare clinical outcomes between percutaneous needle fasciotomy (PNF) and collagenase Clostridium histolyticum (CCH) injection for the treatment of Dupuytren's contracture. Materials and Methods A systematic review was performed including all level I-III evidence studies investigating the clinical outcomes of PNF and CCH injection in the treatment of Dupuytren's contracture. Results Five studies (278 CCH patients, 225 PNF patients; 285 CCH fingers, 246 PNF fingers, 405 males, and 98 females) were analyzed. Two randomized studies were level I evidence, one randomized study was level II, and two nonrandomized studies were level III. Two studies analyzed a total of 205 patients, each demonstrating statistically superior outcomes in one outcome measure (contracture improvement and Michigan Hand Questionnaire (MHQ) satisfaction subscore) with PNF, while the remaining three studies demonstrated no significant differences in outcomes between the two techniques. Three studies reported a statistically higher rate of minor complications (local pain, edema, ecchymosis, lymphadenopathy, pruritis) with CCH, while the remaining two studies demonstrated no significant difference in complication rates. Conclusion For the treatment of Dupuytren's contracture, there is some evidence that suggests superior clinical outcomes of PNF compared with CCH and a higher minor complication rate with CCH.

Readability of Patient Education Materials in Physical Medicine and Rehabilitation (PM&R): A Comparative Cross-Sectional Study.

BACKGROUND: Patients are increasingly using the Internet to access health information. Patient awareness and education are crucial to advancing the field of PM&R, but many U.S. adults have insufficient health literacy skills to read and understand patient education materials (PEM), frequently written at the 10th-15th-grade level. Reading ability is key for health literacy, but no previous research has assessed the readability of PEM provided by professional PM&R societies. OBJECTIVES: Evaluate whether the readability of PM&R PEM meets the NIH-recommended eighth-grade reading level; compare readability of PM&R PEM to two commonly accessed patient resources for sports and rehabilitation medicine topics, handouts from the American Academy of Orthopaedic Surgeons (AAOS) and American Academy of Family Physicians (AAFP), whose readability has been previously analyzed. DESIGN: Cross-sectional study. METHODS: Publicly accessible entries within the patient education section of websites sanctioned by professional PM&R societies, as well as the AAOS and AAFP, were analyzed for readability using two validated and widely used tools, the Flesch-Kincaid Grade Level (FKGL) and Simplified Measure of Gobbledygook (SMOG) formulas. Comparative statistics were performed between the three surveyed specialties. MAIN OUTCOME MEASURES: FKGL and SMOG readability scores, which estimate U.S. grade level, or years of education, needed to comprehend text. RESULTS: A total of 167 online PM&R resources were identified and compared to 94 articles from AAOS and 65 from AAFP. Mean SMOG and FKGL levels exceeded the eighth-grade level for both PM&R (SMOG-9.71, 95% CI 9.42-10.0; FKGL-10.35, 95% CI 9.99-10.7) and AAOS (SMOG-9.15, 95% CI 8.96-9.35; FKGL-9.51, 95% CI 9.29-9.74), whereas AAFP met readability guidelines for both measures (SMOG-7.00, 95% CI 6.74-7.27; FKGL-6.76, 95% CI 6.45-7.07). SMOG and FKGL scores suggested significantly higher reading difficulty for PM&R compared to AAOS (SMOG P = .017; FKGL P = .0001) and AAFP (SMOG P < .0001; FKGL P < .0001). Results indicated that 17% of PM&R resources complied with NIH guidelines, vs 8% for AAOS and 83% for AAFP. CONCLUSIONS: The average readability of PM&R PEM exceeds the NIH-recommended and average U.S. adult eighth-grade reading level. The physiatry community can make its patient materials more comprehensible and accessible for patients by providing resources at a more appropriate reading level.

The benefits of combining water and land-based therapy.

As the general population ages and lives longer with chronic disease and related disability, an increasing number of individuals may be pre-cluded from participating and excelling in traditional land-based therapy or exercise alone, despite its known benefits. This article discusses the benefits of water as an exercise and therapeutic medium, as well as the value of combining both water and land modalities, which enhance the benefits of exercise synergistically. This combined water and land approach has the potential to help clients achieve greater therapeutic benefits and clinical outcomes. As an example, described in this article are the rationale and basic framework for one treatment paradigm supported by research literature, the Burdenko Method, which has utilized combined exercise in water and on land for over four decades. These perspectives will hopefully foster increased understanding and application of exercise principles and programs outside of traditional land-based approaches.

Trajectories of Quality of Life and Associated Risk Factors in Patients With Knee Osteoarthritis: Findings From the Osteoarthritis Initiative.

OBJECTIVE: Knee osteoarthritis (OA) has a significant impact on quality of life (QOL). Although QOL is generally thought to diminish over time, it is unknown whether different patient groups demonstrate unique patterns of change in QOL. We sought to identify and characterize QOL trajectories in knee OA. DESIGN: This prospective cohort study included 1013 individuals with symptomatic knee OA from the osteoarthritis initiative. We used group-based trajectory modeling to identify distinct temporal patterns of change in the Knee Injury and Osteoarthritis Outcome Score QOL subscale for 8 yrs. Baseline covariates included age, sex, ethnicity, education, co-morbidities, body mass index, substance use, depression, knee pain, and functional tests. RESULTS: Group-based trajectory modeling revealed the following three distinct QOL trajectories: a high QOL trajectory (32% of the cohort) experiencing improvement for 8 yrs as well as moderate (49%) and low QOL (20%) trajectories maintaining similar levels over time. Low QOL trajectory membership was significantly associated with younger age (P < 0.001), nonwhite race (P < 0.001), less education (P < 0.001), more co-morbidities (P < 0.001), higher body mass index (P < 0.001), and more depressive symptoms (P < 0.001). Higher QOL trajectory members were less likely to undergo knee replacement surgery (P < 0.001). CONCLUSIONS: Distinct QOL trajectories exist in knee OA and are associated with modifiable factors, with a subset of patients showing potential to improve their QOL over time.

Diagnostic Criteria and Clinical Outcomes in Sarcopenia Research: A Literature Review.

By the sixth decade of life, nearly one quarter of the population has substantial muscle atrophy, or sarcopenia. Despite the creation of a standardized definition of sarcopenia by the European Working Group on Sarcopenia in Older People, variability may exist in the diagnostic criteria utilized for clinical sarcopenia research. The primary objectives of this review were to characterize diagnostic criteria used for measurement of sarcopenia in original studies, and to describe associations between sarcopenia and important clinical outcomes. We performed a literature review of the term "sarcopenia" in PubMed. Inclusion criteria were English language, original data, a clear and specific definition for diagnosing sarcopenia, and the analysis of sarcopenia's effect on a clinical outcome. A total of 283 studies met inclusion criteria. More than half of the included sarcopenia investigations were level IV studies (54.1%), while 43.1% provided level II evidence. Under one third (27.6%) of studies examined sarcopenia with regard to surgical outcomes. In terms of diagnostic criteria for sarcopenia, 264 (93.3%) studies used measures of skeletal muscle mass, with dual energy X-ray absorptiometry (DEXA) being the most common modality (43.6%). Sarcopenia was found to be a consistent predictor of chronic disease progression, all-cause mortality, poorer functional outcomes, and postoperative complications. In conclusion, there is substantial evidence that sarcopenia impacts both medical and surgical outcomes. However, current research has utilized heterogeneous diagnostic criteria for sarcopenia. Further efforts to standardize the modalities used to diagnose sarcopenia in clinical research and practice will help strengthen our ability to study this important phenomenon.

HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome.

Immunophenotypic differences between closely related human leukocyte antigen (HLA) alleles have been associated with divergent clinical outcomes in infection, autoimmunity, transplantation and drug hypersensitivity. Here we explore the impact of micropolymorphism on peptide antigen presentation by three closely related HLA molecules, HLA-B*57:01, HLA-B*57:03 and HLA-B*58:01, that are differentially associated with the HIV elite controller phenotype and adverse drug reactions. For each allotype, we mine HLA ligand data sets derived from the same parental cell proteome to define qualitative differences in peptide presentation using classical peptide binding motifs and an unbiased statistical approach. The peptide repertoires show marked qualitative overlap, with 982 peptides presented by all allomorphs. However, differences in peptide abundance, HLA-peptide stability, and HLA-bound conformation demonstrate that HLA micropolymorphism impacts more than simply the range of peptide ligands. These differences provide grounds for distinct immune reactivity and insights into the capacity of micropolymorphism to diversify immune outcomes.