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Purpose: Intensive support teams (ISTs) are often poorly understood, despite reports of their effectiveness in managing behaviour that challenges for individuals with an intellectual disability. This paper aims to contribute to the understanding of ISTs through evaluating one IST's process and their use of positive behaviour support (PBS) as an intervention. Design/methodology/approach: Participants were obtained from the ISTs discharge database, and pre- and post-intervention data from these participants was used for analysis. Findings: Three-paired sample t-tests found that there were significant differences between pre- and post-scores on the behaviour problem inventory, Health of the Nation Outcomes Scale for people with Learning Disabilities and periodic service reviews, which measure quality of targeted, individualised support. This indicates that challenging behaviour frequency and severity were lower post-intervention, quality of life improved post-intervention and staff teams implemented recommended strategies more consistently by the end of the intervention. Originality/value: This service evaluation captured data over seven-year period, which helps to contribute to the understanding of the effectiveness of ISTs and the PBS framework. [ABSTRACT FROM AUTHOR]

The critically endangered hawksbill sea turtle (Eretmochelys imbricata) is of conservation concern worldwide. Conservation actions which act to reduce high levels of embryonic mortality aid to boost hatchling production. At Cousine Island, Seychelles, a mixed management method has been adopted to maximize the number of hatchlings entering the ocean. We examined the effectiveness of a hatchery at increasing hatching and emergence success from four seasons of data (2017–2021). Hatchery nests had significantly higher hatching and emergence success across all years relative to nests left in situ (i.e., natural), with inter‐annual variation observed. A greater percentage of in situ clutches was found to be influenced by both crab activity and predation as compared to relocated clutches. Overall, the mixed management approach increased hatching success (mean = 75.1%) relative to the various nest management techniques previously used (2004/2005–2016/2017; mean = 63.5%). By mitigating external influences such as tidal flooding, beach erosion, and crab activity/predation, this study provides evidence for the success of a hatchery in directly increasing hatchling recruitment. Strict and careful hatchery management as well as timely and efficient relocation procedures are needed to minimize potential negative effects of nest relocation. [ABSTRACT FROM AUTHOR]

Globally cannabis regulations are rapidly changing. In recent years social and political pressure, not science, has driven this change. Experience from jurisdictions that have implemented regulatory change, although relatively new, should be used to inform future policy development for other jurisdictions, assisting in addressing the wicked problem that cannabis regulations present. This review aimed to elicit underlying themes from a broad range of literature exploring the effects of regulatory change relating to cannabis. To achieve this a meta-narrative theoretical approach using inductive constant comparative analysis was used to synthesize data until thematic saturation was reached. Following a systematic literature search, 92 papers were analyzed before thematic saturation was complete. Five super-ordinate themes emerged that observed the societal and health effects following legislative and regulatory change: Normalization; Economics; Gatekeeping; Community and Health. These themes, empirically derived through a formal qualitative approach, were considered regarding cultural contexts, providing an understanding of how cannabis regulation is changing the social landscape. Consideration of the themes during future research may provide a focus point for the discussion of legislation and policy, not only relating to cannabis, but also other broad-ranging areas such as social policy, welfare, education and health. [ABSTRACT FROM AUTHOR]

We compared clinical outcomes between different starting doses of cabozantinib in a retrospective analysis of 87 mRCC patients. Although patients treated with full starting dose had improved clinical outcomes, this was likely driven by underlying disease characteristics. We also found that hypertension, hand-foot skin reaction and mucositis were associated with improved outcomes. This important real-world data in the standard-of-care setting may be informative for practicing medical oncologists. Background: Full dose cabozantinib for metastatic renal cell carcinoma (mRCC) is 60 mg, but adverse events (AEs) may require dose reductions. Limited data exist comparing efficacy among cabozantinib doses. We compared AEs and clinical outcomes in mRCC patients treated with full vs. reduced starting cabozantinib dose. Methods: We performed a retrospective analysis of 87 mRCC patients treated with cabozantinib at Winship Cancer Institute from 2016 to 2019. Overall survival (OS), progression-free survival (PFS), and objective response (OR) rate measured clinical outcomes. AEs were collected from clinic notes and the most common were hypertension, mucositis/hand-foot skin reaction (HFSR), or gastrointestinal toxicity. Univariate analysis (UVA) between starting doses and AEs with clinical outcomes was performed using logistic regression model. Multivariable analysis was also performed using Cox proportional hazard model. Results: Most patients were men (71%) with clear-cell RCC (72%). The majority were IMDC intermediate (58%) or poor (35%) risk. One third received first-line cabozantinib and 64% had =3 baseline metastatic sites. Most patients (68%) required dose reduction from 60 mg or started at reduced dose without escalation. Reduced dose patients were more likely to have =3 distant metastatic sites (70% vs. 58%) and =2 prior lines of systemic therapy (50% vs. 40%) compared to full dose patients. UVA revealed a trend towards shorter OS (HR: 1.78, P = .095), PFS (HR: 1.50, P = .107), and lower chance of OR (HR:0.42, P = .149) among reduced dose patients. This trend did not hold in Multivariable analysis (OS HR: 1.20, P = .636; PFS HR: 1.23, P = .4662). Mucositis/HFSR and hypertension were significantly associated with improved outcomes in UVA. Conclusions: Although we found a trend favoring full dose cabozantinib, this is likely due to worse baseline disease characteristics among patients starting on a reduced dose. Hypertension and mucositis/HFSR may be associated with improved outcomes. Larger studies are warranted to validate these findings. [ABSTRACT FROM AUTHOR]

This study examined whether individuals who were assaultive at a forensic psychiatric inpatient hospital were more likely to be referred for malingering assessment and whether there was a difference in assaultive behavior between individuals who had non-valid test performance (NVTP) on Performance Validity Tests (PVTs) and those who demonstrated valid test performance (VTP). Of 136 assessments that met inclusion criteria, there were no statistically significant differences in inpatient aggression between the NVTP and VTP groups. However, when inpatient aggression of those 136 subjects was compared to the base rates of inpatient aggression in the general hospital population, a significant difference was found, suggesting that those patients who were referred for malingering testing by their treatment team had higher rates of inpatient aggression than the general hospital population. Implications regarding the role of clinical judgment in identifying individuals who are malingering will be discussed. [ABSTRACT FROM AUTHOR]

Objective: To define a new anatomic relationship in pediatric sinus surgery, assessing the maxillary roof as a constant safe landmark to avoid skull base injury in the pediatric population. Study Design: Retrospective analysis. Setting: Tertiary care children hospital. Subjects and Methods: A retrospective analysis was performed of all computed tomography scans of the sinuses and facial bones at the emergency department of a tertiary children's hospital over the course of a year. Radiographic measurements included the lowest cribriform plate and planum sphenoidale (PS) heights, or posterior skull base when not yet pneumatized, as well as the highest maxillary roof height. The nasal floor was used for reference. Statistics were performed via Shapiro-Wilks test with a P -value of.05 indicating statistical significance. Results: Three hundred and seven unique scans were reviewed (38.9% female; n = 122; P =.58). Age stratification was based on previously described sinus growth patterns. In all patients, the maximum maxillary height was inferior to the lowest measured cribriform lamella and PS (P <.001; CI, 98.5%-99%). Inter- and intrarater reliability and accuracy were verified through blinded review and re-review (ρ =.99 and.98 respectively, P ≤.001). The validity of sole coronal measurements due to incomplete sagittal reformatting was also confirmed (ρ = 1.00, P ≤.001). Conclusion: Despite variation in sinus growth and development in children, the current study demonstrated the validity of the maxillary sinus roof as a constant safe landmark in the pediatric population, offering a novel anatomic relationship for teaching safety in performing pediatric sinus surgery. Level of Evidence: 4 [ABSTRACT FROM AUTHOR]

Orientia tsutsugamushi causes scrub typhus, a potentially fatal infection that threatens over one billion people. Nuclear translocation of the transcription factor, NF-κB, is the central initiating cellular event in the antimicrobial response. Here, we report that NF-κB p65 nuclear accumulation and NF-κB-dependent transcription are inhibited in O. tsutsugamushi infected HeLa cells and/or primary macrophages, even in the presence of TNFα. The bacterium modulates p65 subcellular localization by neither degrading it nor inhibiting IκBα degradation. Rather, it exploits host exportin 1 to mediate p65 nuclear export, as this phenomenon is leptomycin B-sensitive. O. tsutsugamushi antagonizes NF-κB-activated transcription even when exportin 1 is inhibited and NF-κB consequently remains in the nucleus. Two ankyrin repeat-containing effectors (Anks), Ank1 and Ank6, each of which possess a C-terminal F-box and exhibit 58.5% amino acid identity, are linked to the pathogen’s ability to modulate NF-κB. When ectopically expressed, both translocate to the nucleus, abrogate NF-κB-activated transcription in an exportin 1-independent manner, and pronouncedly reduce TNFα-induced p65 nuclear levels by exportin 1-dependent means. Flag-tagged Ank 1 and Ank6 co-immunoprecipitate p65 and exportin 1. Both also bind importin β1, a host protein that is essential for the classical nuclear import pathway. Importazole, which blocks importin β1 activity, abrogates Ank1 and Ank6 nuclear translocation. The Ank1 and Ank6 regions that bind importin β1 also mediate their transport into the nucleus. Yet, these regions are distinct from those that bind p65/exportin 1. The Ank1 and Ank6 F-box and the region that lies between it and the ankyrin repeat domain are essential for blocking p65 nuclear accumulation. These data reveal a novel mechanism by which O. tsutsugamushi modulates the activity and nuclear transport of NF-κB p65 and identify the first microbial proteins that co-opt both importin β1 and exportin 1 to antagonize a critical arm of the antimicrobial response. [ABSTRACT FROM AUTHOR]

Institutional aggression within forensic psychiatric facilities is a common problem that has not been adequately researched. Several studies have shown that a relatively small portion of the at-risk patient population is responsible for the majority of inpatient aggression. The present study compared a sample of forensic inpatients who engaged in repeated and severe aggression towards staff or peers with a sample of non-aggressive inpatients that were matched for age, gender, legal commitment type, and hospital length of stay. The discriminant model correctly predicted 74.2% of those classified as perpetrating severe and repeated aggression and 87.1% of those classified as non-aggressive within the institution. The model accounted for 51% of the variance. The predictors included variables traditionally associated with violence risk, such as the presence of a personality disorder. However, the model also included suicide attempts and psychiatric hospitalization as a juvenile; two predictors that have not been commonly included in community violence measures. These findings identify unique predictors of highly aggressive patients who cause serious injuries to other patients and staff. The early identification and management of individuals with increased risk for severe and repeated aggression is an important consideration for triaging inpatients at risk for this type of aggression. [ABSTRACT FROM PUBLISHER]

Background HIV-1 Vif promotes the degradation of host anti-retroviral factor family, APOBEC3 proteins via the recruitment of a multi-subunit E3 ubiquitin ligase complex. The complex is composed of a scaffold protein, Cullin 5 (Cul5), RING-box protein (Rbx), a SOCS box binding protein complex, Elongins B/C (Elo B/C), as well as newly identified host co-factor, core binding factor beta (CBF-β). Cul5 has previously been shown to bind amino acids within an HCCH domain as well as a PPLP motif at the C-terminus of Vif; however, it is unclear whether Cul5 binding requires additional regions of the Vif polypeptide. 2 Results Here, we provide evidence that an amino terminal region of full length Vif is necessary for the Vif-Cul5 interaction. Single alanine replacement of select amino acids spanning residues 25-30 (25VXHXMY30) reduced the ability for Vif to bind Cul5, but not CBF-β or Elo B/C in pull-down experiments. In addition, recombinant Vif mutants had a reduced binding affinity for Cul5 compared to wild-type as measured by isothermal titration calorimetry. N-terminal mutants that demonstrated reduced Cul5 binding were also unable to degrade APOBEC3G as well as APOBEC3F and were unable to restore HIV infectivity, in the presence of APOBEC3G. Although the Vif N-terminal amino acids were necessary for Cul5 interaction, the mutation of each residue to alanine induced a change in the secondary structure of the Vif-CBF-β-Elo B/C complex as suggested by results from circular dichroism spectroscopy and size-exclusion chromatography experiments. Surprisingly, the replacement of His108 to alanine also contributed to the Vif structure. Thus, it is unclear whether the amino acids contribute to a direct interaction with Cul5 or whether the amino acids are responsible for the structural organization of the Vif protein that promotes Cul5 binding. Conclusions Taken together, we propose a novel Vif N-terminal motif that is responsible for Vif recruitment of Cul5. Motifs in Vif that are absent from cellular proteins represent attractive targets for future HIV pharmaceutical design. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus-1 (HIV-1) viral infectivity factor (Vif) is essential for viral replication because of its ability to eliminate the host's antiviral response to HIV-1 that is mediated by the APOBEC3 family of cellular cytidine deaminases. Vif targets these proteins, including APOBEC3G, for polyubiquitination and subsequent proteasome-mediated degradation via the formation of a Cullin5-ElonginB/C-based E3 ubiquitin ligase. Determining how the cellular components of this E3 ligase complex interact with Vif is critical to the intelligent design of new antiviral drugs. However, structural studies of Vif, both alone and in complex with cellular partners, have been hampered by an inability to express soluble full-length Vif protein. Here we demonstrate that a newly identified host regulator of Vif, core-binding factor-beta (CBFβ), interacts directly with Vif, including various isoforms and a truncated form of this regulator. In addition, carboxyl-terminal truncations of Vif lacking the BC-box and cullin box motifs were sufficient for CBFβ interaction. Furthermore, association of Vif with CBFβ, alone or in combination with Elongin B/C (EloB/C), greatly increased the solubility of full-length Vif. Finally, a stable complex containing Vif-CBFβ-EloB/C was purified in large quantity and shown to bind purified Cullin5 (Cul5). This efficient strategy for purifying Vif-Cul5-CBFβ-EloB/C complexes will facilitate future structural and biochemical studies of Vif function and may provide the basis for useful screening approaches for identifying novel anti-HIV drug candidates. [ABSTRACT FROM AUTHOR]

Abstract: The use of antimicrobials in commercial broiler poultry production results in the presence of drug-resistant bacteria shed in the excreta of these birds. Because these wastes are largely land-disposed these pathogens can affect the surrounding environment and population. In this analysis, we characterized the survival of antimicrobial-resistant enterococci and staphylococci and resistance genes in poultry litter. Temperature, moisture, and pH were measured in the litter over a 120-day period from storage sheds at three conventional US broiler chicken farms, as well as colony-forming units of Enterococcus spp. and Staphylococcus spp. Selected isolates from each sampling event were tested for resistance to eight antimicrobials used in poultry feeds as well as the presence of resistance genes and mobile genetic elements. Temperatures greater than 60°C were only intermittently observed in the core of the litter piles. Both antimicrobial-resistant enterococci and staphylococci, as well as resistance genes persisted throughout the 120-day study period. Resistance genes identified in the study include: erm(A), erm(B), erm (C), msr(A/B), msr(C), and vat(E). This study indicates that typical storage practices of poultry litter are insufficient for eliminating drug-resistant enterococci and staphylococci, which may then be released into the environment through land disposal. [Copyright &y& Elsevier]

In the past decade, immune checkpoint inhibitors (ICI) have been approved for treatment of genitourinary malignancies and have revolutionized the treatment landscape of these tumors. However, despite the remarkable success of these therapies in some GU malignancies, many patients' tumors do not respond to these therapies, and others may experience significant side effects, such as immune-related adverse events (iRAEs). Accordingly, biomarkers and improved prognostic tools are critically needed to help predict which patients will respond to ICI, predict and mitigate risk of developing immune-related adverse events, and inform personalized choice of therapy for each patient. Ongoing clinical and preclinical studies continue to provide an increasingly robust understanding of the mechanisms of the response to immunotherapy, which continue to inform biomarker development and validation. Herein, we provide a comprehensive review of biomarkers of the response to immunotherapy in GU tumors and their role in selection of therapy and disease monitoring. [ABSTRACT FROM AUTHOR]

Background: As targeted treatments for amyloid transthyretin cardiomyopathy (ATTR‐CM) are becoming available, we aim to characterize the rates of ventricular arrhythmias (VAs), implantable cardioverter‐defibrillator (ICD) utilization, and their impact on survival. Methods: This is a retrospective cohort study of 130 patients with ATTR‐CM diagnosed at Emory University's Cardiac Amyloidosis Center between April 2012 and September 2020. VAs were defined as nonsustained or sustained ventricular tachycardia and ventricular fibrillation. Results: Of 130 patients, 42 had wild‐type disease (wtATTR) and 88 had hereditary variants (hATTR), most commonly Val122Ile (89%). At ATTR‐CM diagnosis, 80 (62%) patients had EF ≤ 40% consistent with systolic heart failure. Of the 69 (53%) patients with documented VAs significantly higher rates occurred among those with EF ≤ 40% compared with EF > 40% (67% vs. 28%, p =.001). Thirty‐two patients (25 hATTR, 7 wtATTR) had primary prevention ICDs implanted. Eight (25%) of these patients received appropriate ICD therapy while two (6%) experienced inappropriate therapy. Comparing patients with EF ≤ 35% with and without ICDs did not reveal any survival difference (3.3 ± 0.5 vs. 2.8 ± 0.4 years, p =.699). Conclusions: High rates of VAs and appropriate ICD therapy were found among a unique cohort of largely hereditary ATTR‐CM patients with a high rate of systolic heart failure. [ABSTRACT FROM AUTHOR]

The article provides information on team-based learning (TBL) introduced into online seven-week prematriculation courses (PMCs) as the pedagogical approach to learning biomedical sciences, replacing an entirely lecture-based format. Topics discussed include communications platform used, modifications to traditional TBL readiness assurance tests (RATs) that were made to promote problem-solving and collaboration, and lessons learned from the TBL model.

Objective: An inner-city hospital purchased a local hotel to provide support, digital engagement, skill development groups and referrals to partner agencies. Being aware of the hotel's importance to the local community, we sought feedback on a model of care relevant to perceived gaps and needs in support for mental health. Methods: Four online focus groups included healthcare professionals, nominated opinion leaders from local Non-Government Organisations (NGOs), consumers and carers to reflect a range of views. Focus group data were qualitatively analysed. Results: Participants made useful suggestions about WHAT educational, preventative and therapeutic services were needed. They emphasised the importance of HOW people engage with the service, the balance between accessibility and security. Other themes included targeting people with limited health literacy, integration with existing services, building on site heritage and ongoing evaluation of objectives and needs. Conclusions: This pilot study demonstrated clear support for providing safe and welcoming access to services, with resources and access to services to improve their health and wellbeing built on principles of social justice and inclusion. Participants had constructive ideas of what was needed, and ongoing patient and public research is anticipated. [ABSTRACT FROM AUTHOR]

Objectives: Review the incidence and factors associated with respiratory compromise requiring intensive care unit level interventions in children with planned admission to the pediatric intensive care unit (PICU) following tonsillectomy or adenotonsillectomy (T/AT). Study design: Retrospective cohort study. Methods: Review of all patients with PICU admissions following T/AT from 2015 to 2020 at a tertiary care pediatric hospital. Patient demographics, underlying comorbidities, operative data, and respiratory complications during PICU admission were extracted. Results: Seven hundred and seventy-two patients were admitted to the PICU following T/AT, age 6.1 ± 4.6 years. All children were diagnosed with obstructive sleep apnea or sleep-disordered breathing (mean pre-operative apnea-hypopnea index 29 ± 26.5 and O2 nadir 77.1% ± 11.1). Neuromuscular disease, enteral feed dependence, and obesity were common findings (N = 240 (31%), N = 106 (14%), and N = 209 (27%) respectively). Overall, 29 patients (3.7%) developed respiratory compromise requiring PICU-level support, defined as new-onset continuous or bilevel positive airway pressure support (n = 25) or reintubation (n = 9). Three patients were diagnosed with pulmonary edema. Multivariable regression analysis demonstrated pre-operative oxygen nadir and enteral feed dependence were associated with respiratory compromise (OR = 0.97, 95% CI 0.94-0.99, P =.04; OR = 6.3, 95% CI 2.36-52.6, P =.001 respectively). Conclusions: Our study found respiratory compromise in 3.7% of patients with planned PICU admissions following T/AT. Oxygen nadir and enteral feeds were associated with higher respiratory compromise rates. Attention should be given to these factors in planning for post-operative disposition. [ABSTRACT FROM AUTHOR]

The article focuses on the effective direct student observation strategies in neurology. It informs that direct observation of histories and physicals rarely occurs in the training of neurology. It is suggested that doctors should be confident about its usefulness in busy clinical settings. This strategy was also applied on a student and the author in which the student interviewed the patient whereas the author observed and generated documentation.

The COVID-19 pandemic caused graduate medical education (GME) programs to pivot to virtual interviews (VIs) for recruitment and selection. This systematic review synthesizes the rapidly expanding evidence base on VIs, providing insights into preferred formats, strengths, and weaknesses. PubMed/MEDLINE, Scopus, ERIC, PsycINFO, MedEdPublish, and Google Scholar were searched from 1 January 2012 to 21 February 2022. Two authors independently screened titles, abstracts, full texts, performed data extraction, and assessed risk of bias using the Medical Education Research Quality Instrument. Findings were reported according to Best Evidence in Medical Education guidance. One hundred ten studies were included. The majority (97%) were from North America. Fourteen were conducted before COVID-19 and 96 during the pandemic. Studies involved both medical students applying to residencies (61%) and residents applying to fellowships (39%). Surgical specialties were more represented than other specialties. Applicants preferred VI days that lasted 4–6 h, with three to five individual interviews (15–20 min each), with virtual tours and opportunities to connect with current faculty and trainees. Satisfaction with VIs was high, though both applicants and programs found VIs inferior to in-person interviews for assessing 'fit.' Confidence in ranking applicants and programs was decreased. Stakeholders universally noted significant cost and time savings with VIs, as well as equity gains and reduced carbon footprint due to eliminating travel. The use of VIs for GME recruitment and selection has accelerated rapidly. The findings of this review offer early insights that can guide future practice, policy, and research. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic spurred an abrupt transition away from in-person educational activities. This systematic review investigated the pivot to online learning for nonclinical undergraduate medical education (UGME) activities and explored descriptions of educational offerings deployed, their impact, and lessons learned. The authors systematically searched four online databases and conducted a manual electronic search of MedEdPublish up to December 21, 2020. Two authors independently screened titles, abstracts and full texts, performed data extraction and assessed risk of bias. A third author resolved discrepancies. Findings were reported in accordance with the STORIES (STructured apprOach to the Reporting in healthcare education of Evidence Synthesis) statement and BEME guidance. Fifty-six articles were included. The majority (n = 41) described the rapid transition of existing offerings to online formats, whereas fewer (n = 15) described novel activities. The majority (n = 27) included a combination of synchronous and asynchronous components. Didactics (n = 40) and small groups (n = 26) were the most common instructional methods. Teachers largely integrated technology to replace and amplify rather than transform learning, though learner engagement was often interactive. Thematic analysis revealed unique challenges of online learning, as well as exemplary practices. The quality of study designs and reporting was modest, with underpinning theory at highest risk of bias. Virtually all studies (n = 54) assessed reaction/satisfaction, fewer than half (n = 23) assessed changes in attitudes, knowledge or skills, and none assessed behavioral, organizational or patient outcomes. UGME educators successfully transitioned face-to-face instructional methods online and implemented novel solutions during the COVID-19 pandemic. Although technology's potential to transform teaching is not yet fully realized, the use of synchronous and asynchronous formats encouraged virtual engagement, while offering flexible, self-directed learning. As we transition from emergency remote learning to a post-pandemic world, educators must underpin new developments with theory, report additional outcomes and provide details that support replication. [ABSTRACT FROM AUTHOR]

Abstract: Rosai Dorfman disease (RD), also known as sinus histiocytosis with massive lymphadenopathy (SHML), is a benign histiocytic proliferative condition of unsubstantiated etiology that most often presents as bilateral painless cervical lymphadenopathy. Head and neck manifestations of RD are diverse but most commonly present as massive cervical lymphadenopathy. Interestingly, a retropharyngeal fluid collection has never been described as a sequelae of RD. Our objective is to present a novel case of a 9-year old female with RD that suffered from recurrent retropharyngeal phlegmon and to discuss diagnostic and treatment recommendations for this disease process. [Copyright &y& Elsevier]

For decades, aggressive behavior among psychiatric inpatients has been identified as disruptive to the therapeutic environment and a workplace hazard. Most previous research has focused on individual patient risk factors with less attention paid to the situational, environmental, or therapeutic milieu factors that could influence violence rates. This review outlines the prominent areas discussed in situational factor research and presents recent theoretical models that integrate these factors. Based on the identified shortcomings in the available literature, suggestions for future research directions are offered. [Copyright &y& Elsevier]

The human APOBEC3 cytidine deaminases are potent inhibitors of diverse retroviruses, including human immunodeficiency virus-1 (HIV-1). HIV-1 Vif forms an E3 ubiquitin ligase complex with cullin 5 (CUL5), elongin B and elongin C , which promotes the polyubiquitination and degradation of APOBEC3 substrates. Here we demonstrate in human T cells that core binding factor ? (CBF-?) is a key regulator of the evasion of HIV-1 from the host defence mediated by APOBEC3. CBF-?, the non-DNA-binding subunit of a heterodimeric transcription factor, regulates the folding and DNA-binding activity of partner RUNX family proteins, which have important roles in the development and differentiation of diverse cell types, including T lymphocytes. In our study, knockdown of endogenous CBF-? blocked Vif-induced APOBEC3G polyubiquitination and degradation. CBF-? was not required for the interaction between Vif and APOBEC3G, yet was essential for the assembly of the Vif-CUL5 E3-ubiquitin-ligase complex. CBF-? proved to be a unique regulator of primate lentiviral Vif and not a general component of the CUL5 E3 ubiquitin ligase. We show that Vif and CBF-? physically interact, and that the amino-terminal region of Vif is required for this interaction. Furthermore, interactions with Vif required regions in CBF-? that are not involved in RUNX protein binding. Considering the importance of the interaction between Vif and CBF-?, disrupting this interaction represents an attractive pharmacological intervention against HIV-1. [ABSTRACT FROM AUTHOR]

Background: The human immune response to mercury is not well characterized despite the body of evidence that suggests that Hg can modulate immune responses, including the induction of autoimmune disease in some mouse models. Dysregulation of cytokine signaling appears to play an important role in the etiology of Hg-induced autoimmunity in animal models. Objectives: In this study, we systematically investigated the human immune response to Hg in vitro in terms of cytokine release. Methods: Human peripheral blood mononuclear cells (PBMCs) were isolated from 20 volunteers who donated blood six separate times. PBMCs were cultured with lipopolysaccharide and concentrations of mercuric chloride (HgCl2) up to 200 nM. Seven cytokines representing important pathways in physiologic and pathologic immune responses were measured in supernatants. We used multilevel models to account for the intrinsic clustering in the cytokine data due to experimental design. Results: We found a consistent increase in the release of the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α, and concurrent decrease in release of the antiinflammatory cytokines interleukin 1-receptor antagonist (IL-1Ra) and IL-10 in human PBMCs treated with subcytotoxic concentrations of HgCl2. IL-4, IL-17, and interferon-γ increased in a concentration-response manner. These results were replicated in a second, independently recruited population of 20 different volunteers. Conclusions: Low concentrations of HgCl2 affect immune function in human cells by dysregulation of cytokine signaling pathways, with the potential to influence diverse health outcomes such as susceptibility to infectious disease or risk of autoimmunity. [ABSTRACT FROM AUTHOR]

Use of antibiotics as feed additives in poultry production has been linked to the presence of antibiotic resistant bacteria in farm workers, consumer poultry products and the environs of confined poultry operations. There are concerns that these resistant bacteria may be transferred to communities near these operations; however, environmental pathways of exposure are not well documented. We assessed the prevalence of antibiotic resistant enterococci and staphylococci in stored poultry litter and flies collected near broiler chicken houses. Drug resistant enterococci and staphylococci were isolated from flies caught near confined poultry feeding operations in the summer of 2006. Susceptibility testing was conducted on isolates using antibiotics selected on the basis of their importance to human medicine and use in poultry production. Resistant isolates were then screened for genetic determinants of antibiotic resistance. A total of 142 enterococcal isolates and 144 staphylococcal isolates from both fly and poultry litter samples were identified. Resistance genes erm(B), erm(A), msr(C), msr(A/B) and mobile genetic elements associated with the conjugative transposon Tn916, were found in isolates recovered from both poultry litter and flies. Erm(B) was the most common resistance gene in enterococci, while erm(A) was the most common in staphylococci. We report that flies collected near broiler poultry operations may be involved in the spread of drug resistant bacteria from these operations and may increase the potential for human exposure to drug resistant bacteria. [Copyright &y& Elsevier]

Introduction/Aim: Eptacog beta is a recombinant activated human factor VII approved to treat and control bleeding in haemophilia A and B patients with inhibitors. Emicizumab is a factor VIIIa mimetic antibody approved for prophylactic treatment of haemophilia A with and without inhibitors (HAI and HA, respectively). Inhibitor patients treated with emicizumab should expect breakthrough bleeding that requires bypassing agent treatment to restore haemostasis. The aim of this study is to quantify the in vitro thrombin generation induced by the addition of eptacog beta to HAI and HA plasma containing emicizumab. Methods: Thrombin generation assays were performed using HAI and HA plasma. Thrombin generation parameters were examined using a fixed effects model with inhibitor titre, eptacog beta concentration and emicizumab concentration as main effects, and eptacog beta concentration with inhibitor and emicizumab concentration with inhibitor as interaction effects. Results: A significant increase in peak thrombin, ETP and velocity was observed when combinations of eptacog beta (0, 1, 2 or 5 µg/ml) and emicizumab (0, 50 or 100 µg/ml) were evaluated in HA and HAI plasma; the effect remained below that observed in Normal Plasma (NP). A small shortening of lag time below that of NP was observed. Conclusions: Eptacog beta and emicizumab induced thrombin generation in haemophilia A plasma (with and without inhibitors) with the thrombin generation parameters remaining below those of normal plasma. These data provide in vitro proof of concept supporting the concept of use of eptacog beta for the treatment and control of breakthrough bleeding in patients on emicizumab prophylaxis. [ABSTRACT FROM AUTHOR]

BACKGROUNDTo understand the features of a replicating vaccine that might drive potent and durable immune responses to transgene-encoded antigens, we tested a replication-competent adenovirus type 4 encoding influenza virus H5 HA (Ad4-H5-Vtn) administered as an oral capsule or via tonsillar swab or nasal spray.METHODSViral shedding from the nose, mouth, and rectum was measured by PCR and culturing. H5-specific IgG and IgA antibodies were measured by bead array binding assays. Serum antibodies were measured by a pseudovirus entry inhibition, microneutralization, and HA inhibition assays.RESULTSAd4-H5-Vtn DNA was shed from most upper respiratory tract-immunized (URT-immunized) volunteers for 2 to 4 weeks, but cultured from only 60% of participants, with a median duration of 1 day. Ad4-H5-Vtn vaccination induced increases in H5-specific CD4+ and CD8+ T cells in the peripheral blood as well as increases in IgG and IgA in nasal, cervical, and rectal secretions. URT immunizations induced high levels of serum neutralizing antibodies (NAbs) against H5 that remained stable out to week 26. The duration of viral shedding correlated with the magnitude of the NAb response at week 26. Adverse events (AEs) were mild, and peak NAb titers were associated with overall AE frequency and duration. Serum NAb titers could be boosted to very high levels 2 to 5 years after Ad4-H5-Vtn vaccination with recombinant H5 or inactivated split H5N1 vaccine.CONCLUSIONReplicating Ad4 delivered to the URT caused prolonged exposure to antigen, drove durable systemic and mucosal immunity, and proved to be a promising platform for the induction of immunity against viral surface glycoprotein targets.TRIAL REGISTRATIONClinicalTrials.gov NCT01443936 and NCT01806909.FUNDINGIntramural and Extramural Research Programs of the NIAID, NIH (U19 AI109946) and the Centers of Excellence for Influenza Research and Surveillance (CEIRS), NIAID, NIH (contract HHSN272201400008C). [ABSTRACT FROM AUTHOR]

Background: Combination regimens that include immune checkpoint (ICI) and vascular endothelial growth factor (VEGF) inhibition have opened the door to new treatment opportunities for patients with metastatic renal cell carcinoma (mRCC). While these treatment options have provided improved tolerability and better outcomes compared to older regimens, many patients still experience a myriad of treatment-related adverse events. Given that these regimens were recently approved for mRCC, the complete side effect profile may not be fully elucidated yet.Case Presentation: We report a case of a 73-year old White male with mRCC who was managed with an ICI-VEGF inhibitor combination regimen. He experienced a partial response (Fig. 1) but had side effects including symptomatic cyanosis diagnosed as methemoglobinemia which led to treatment discontinuation. Upon holding his therapy, his methemoglobinemia and cyanosis resolved.Conclusions: Combination VEGF-ICI therapy provide novel regimens for advanced solid tumor malignancies including mRCC. While shown to have improved efficacy in clinical trials, it is crucial that oncologists uncover the full side effect profile of these novel agents especially as their use becomes more standard in the management of advanced malignancies. To our knowledge, this is the first reported case of a patient experiencing symptomatic methemoglobinemia as an adverse event associated with a VEGF-ICI combination regimen. While the cause of this side effect is unclear, in this paper we attempt to elucidate a process that is in line with the mechanism of action of these therapies to explain how these agents, specifically the axitinib, could have caused the methemoglobin to rise to a symptomatic level. [ABSTRACT FROM AUTHOR]

Plasmacytoid dendritic cells (PDCs) and their production of interferon-alpha (IFN-α) are believed to play an important role in human immunodeficiency virus, type I (HIV-1) pathogenesis. PDCs produce IFN-α and other proinflammatory cytokines through stimulation of Toll-like receptor 7 (TLR7) and TLR9 present in endosomal compartments. TLR7 recognizes single-stranded viral RNA, while TLR9 recognizes unmethylated DNA. In this study, we examined the mechanisms that may underlie variations in IFN-α production in response to HIV, and the impact of these variations on HIV pathogenesis. In four distinct cohorts, we examined PDC production of IFN-α upon stimulation with inactivated HIV-1 particles and unmethylated DNA. The signaling cascade of TLR7 bifurcates at the myeloid differentiation protein 88 (MyD88) adaptor protein to induce expression of either IFN-α or TNF-α. To determine whether variations in IFN-α production are modulated at the level of the receptor complex or downstream of it, we correlated production of IFN-α and TNF-α following stimulation of TLR7 or TLR9 receptors. Flow cytometry detection of intracellular cytokines showed strong, direct correlations between IFN-α and TNF-α expression in all four cohorts, suggesting that variations in IFN-α production are not due to variations downstream of the receptor complex. We then investigated the events upstream of TLR binding by using lipid-like vesicles to deliver TLR ligands directly to the TLR receptors, bypassing the need for CD4 binding and endocytosis. Similar tight correlations were found in IFN-α and TNF-α production in response to the TLR ligands. Taken together, these results strongly suggest that differences in IFN-α production depend on the regulatory processes at the level of the TLR7 receptor complex. Additionally, we found no association between IFN-α production before HIV infection and disease progression. [ABSTRACT FROM AUTHOR]

Lymphatic malformations (LMs) are uncommon congenital abnormalities of the lymphatic system. As more than half of these lesions develop in the head and neck, LMs can be life-threatening if associated with airway involvement. LMs necessitate a multidisciplinary treatment approach, frequently including surgery and sclerotherapy. We present a case report of a 32-week pre-term male infant with a massive cervicofacial LM necessitating delivery via ex-utero intrapartum treatment (EXIT). The patient was treated with numerous rounds of sclerotherapy, systemic sirolimus, and surgical debulking, but ultimately died at 4 months of age due to acute pulmonary hemorrhage, which may have been related to sirolimus due to the absence of any other associable organ involvement or derangement. We document the patient's clinical course and treatment regimen, highlighting the myriad modalities employed to treat these challenging lesions, and describe a potentially lethal complication of sirolimus therapy not previously described in the treatment of pediatric LM. [ABSTRACT FROM AUTHOR]

Rickettsial agents are sensed by pattern recognition receptors but lack pathogen-associated molecular patterns commonly observed in facultative intracellular bacteria. Due to these molecular features, the order Rickettsiales can be used to uncover broader principles of bacterial immunity. Here, we used the bacterium Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, to reveal a novel microbial surveillance system. Mechanistically, we discovered that upon A. phagocytophilum infection, cytosolic phospholipase A2 cleaves arachidonic acid from phospholipids, which is converted to the eicosanoid prostaglandin E2 (PGE2) via cyclooxygenase 2 (COX2) and the membrane associated prostaglandin E synthase-1 (mPGES-1). PGE2-EP3 receptor signaling leads to activation of the NLRC4 inflammasome and secretion of interleukin (IL)-1β and IL-18. Importantly, the receptor-interacting serine/threonine-protein kinase 2 (RIPK2) was identified as a major regulator of the immune response against A. phagocytophilum. Accordingly, mice lacking COX2 were more susceptible to A. phagocytophilum, had a defect in IL-18 secretion and exhibited splenomegaly and damage to the splenic architecture. Remarkably, Salmonella-induced NLRC4 inflammasome activation was not affected by either chemical inhibition or genetic ablation of genes associated with PGE2 biosynthesis and signaling. This divergence in immune circuitry was due to reduced levels of the PGE2-EP3 receptor during Salmonella infection when compared to A. phagocytophilum. Collectively, we reveal the existence of a functionally distinct NLRC4 inflammasome illustrated by the rickettsial agent A. phagocytophilum. [ABSTRACT FROM AUTHOR]

To evaluate associations between childhood obesity and post-adenotonsillectomy complications, informing guidelines for postoperative management. The retrospective review assessed outpatient pediatric tonsillectomy/adenoidectomy cases performed at 2 ambulatory surgery centers in 2020. Complications in the recovery unit and within 2 weeks of surgical discharge were reviewed along with clinical and demographic variables. Obesity was defined as sex-specific body mass index-for-age, or weight-for-age if height data were unavailable, at/above the 95th percentile. The 99th percentile served as the threshold for severe obesity. Analyses used Chi-square/Fisher's exact tests and independent-samples t -tests with relative risk or effect sizes. The review included 707 cases (180 patients with obesity). Overall incidence of complications in the recovery unit was 9.1%. Patients with obesity were significantly more likely to require supplemental blow-by oxygen (P =.02); relative risk was 1.65 (95% CI: 1.16–2.35) times greater in the cohort with obesity. Obesity had a small effect on postoperative oxygen saturation nadirs, which were significantly lower among patients with obesity (d = −0.34; P <.001). No differences emerged between cohorts with and without obesity in the incidence of any other complications before or after surgical discharge. Overall incidence of post-discharge returns was 7.9%. Incidence of complications did not vary by obesity severity. From this cohort, childhood obesity without other significant comorbidities may not warrant routine inpatient care following adenotonsillectomy. Patients with obesity should receive additional monitoring for oxygen desaturation events during the first hours of recovery. Further prospective studies should continue to address this important topic. • Childhood obesity alone may not warrant routine inpatient care after tonsillectomy. • Outpatient surgery can be safe for children with obesity if other risks are absent. • Oxygen desaturation in the first hours of recovery was more likely given obesity. • Obesity was not associated with incidence of any other postoperative complications. • Incidence of postoperative complications did not vary by obesity severity. [ABSTRACT FROM AUTHOR]

Opioid prescribing patterns after pediatric tonsillectomy are highly variable, and opioids may not improve pain control compared to over-the-counter pain relievers. We evaluated whether a standardized, opioid-sparing analgesic protocol effectively reduced opioid prescriptions without compromising patient outcomes. A quality improvement project was initiated in July 2019 to standardize analgesic prescribing after hospital-based tonsillectomy with/without adenoidectomy. An electronic order set provided weight-based dosing and defaulted to non-opioid prescriptions (acetaminophen and ibuprofen). Patients ages 0–6 received non-opioid analgesics alone. Patients ages 7–18 received non-opioid analgesics as first-line pain control, and providers could manually add hydrocodone-acetaminophen for breakthrough pain. Opioid prescriptions and quantities were compared for 18 months of cases pre- versus post-standardization. Postoperative returns to the system were reviewed as a balancing measure. From 2018 through 2020, 1817 cases were reviewed. The frequency of opioid prescriptions decreased significantly post-standardization, from 64.9% to 33.5% of cases (P <.001). Opioid prescribing for young children steadily decreased from over 50% to 2.4%. Protocol adherence improved over time; outlier prescriptions were eliminated. Opioid quantities per prescription decreased by 16.3 doses on average (P <.001), and variance decreased significantly post-standardization (P <.001). The incidence of returns to the system did not change (P =.33), including returns for pain or decreased intake (P =.28). An age-based and weight-based analgesic protocol reduced post-tonsillectomy opioid prescriptions without a commensurate increase in returns for postoperative complaints. Standardized protocols can facilitate sustained changes in prescribing patterns and limit potentially unnecessary pediatric opioid exposure. • Standardized post-tonsillectomy analgesic prescribing improved opioid stewardship. • The protocol minimized opioid prescriptions for children under age 7. • Weight-based dosing reduced opioids per prescription by 16.3 doses on average. • Outlier prescriptions were eliminated and protocol adherence improved over time. • Returns for postoperative complaints did not increase under the protocol. [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus type 1 (HIV-1)-encoded virion infectivity factor (Vif) is required to inactivate the host restriction factor APOBEC3 by engaging Cullin 5 (Cul5)-RING ubiquitin ligase (CRL5). Core binding factor beta (CBF-β) is a novel regulator of Vif-CRL5 function; as yet, its mechanism of regulation remains unclear. In the present study, we demonstrate that CBF-β promotion of Vif-CRL5 assembly is independent of its influence on Vif stability and is also a conserved feature of primate lentiviral Vif proteins. Furthermore, CBF-β is critical for the formation of the Vif-ElonginB/ElonginC-Cul5 core E3 ubiquitin ligase complex in vitro. CBF-β from diverse vertebrate species supported HIV-1 Vif function, indicating the conserved nature of Vif-CBF-β interfaces. Considering the importance of the interaction between Vif and CBF-β in viral CRL5 function, disrupting this interaction represents an attractive pharmacological intervention against HIV-1. [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus type 1 (HIV-1)-encoded virion infectivity factor (Vif) is required to inactivate the host restriction factor APOBEC3 by engaging Cullin 5 (Cul5)-RING ubiquitin ligase (CRL5). Core binding factor beta (CBF-β) is a novel regulator of Vif-CRL5 function; as yet, its mechanism of regulation remains unclear. In the present study, we demonstrate that CBF-β promotion of Vif-CRL5 assembly is independent of its influence on Vif stability and is also a conserved feature of primate lentiviral Vif proteins. Furthermore, CBF-β is critical for the formation of the Vif-ElonginB/ElonginC-Cul5 core E3 ubiquitin ligase complex in vitro. CBF-β from diverse vertebrate species supported HIV-1 Vif function, indicating the conserved nature of Vif-CBF-β interfaces. Considering the importance of the interaction between Vif and CBF-β in viral CRL5 function, disrupting this interaction represents an attractive pharmacological intervention against HIV-1. IMPORTANCE HIV-1 encodes virion infectivity factor (Vif) to inactivate its host's antiviral APOBEC3 proteins. Vif triggers APOBEC3 degradation by forming Vif-Cullin 5 (Cul5)-RING ubiquitin ligase (CRL5). Core binding factor beta (CBF-β) is a novel regulator of Vif- CRL5 function whose mechanism of regulation remains poorly defined. In the present study, we demonstrate that the promotion of Vif-CRL5 assembly by CBF-β can be separated from its influence on Vif stability. The promotion of Vif-CRL5 assembly, but not the influence on Vif stability, is conserved among primate lentiviral Vif proteins: we found that CBF-β from diverse vertebrate species supported HIV-1 Vif function. Considering the importance of the interaction between Vif and CBF-β in viral CRL5 function and HIV-1 replication, disrupting this interaction is an attractive strategy against HIV-1. [ABSTRACT FROM AUTHOR]

CBFβ was recently found to be a key regulator of the ability of human immunodeficiency virus type 1 (HIV-1) Vif to overcome host antiviral APOBEC3 proteins. However, the detailed molecular requirements for the Vif-CBFβ interaction are still not clear. Here, we mapped the minimum Vif domain required for CBFβ binding. In terms of CBFβ binding, the Vif N terminus was very sensitive to deletions. We determined that the Vif fragment from residues 5 to 126 was sufficient to form a stable complex with CBFβ in vitro. We also observed that ionic interactions were not the main contributor to the interaction between Vif and CBFβ. Instead, hydrophobic interactions were important for maintaining the Vif-CBFβ complex, since it could be disrupted by nonionic detergent. Site-directed mutagenesis of conserved hydrophobic amino acids revealed novel residues in Vif that were important for CBFβ binding and APOBEC3 inactivation. At least part of the well-characterized HCCH domain (residues 108 to 139) was required to form a stable Vif-CBFβ complex. Thus, the HCCH motif may have a dual role in binding both Cul5 and CBFβ. Considering the importance of Vif in HIV-1 infection, this unique Vif-CBFβ interaction represents an attractive pharmacological intervention target against HIV-1. IMPORTANCE Vif-induced APOBEC3 protein degradation was the first host antiviral mechanism against HIV-1/simian immunodeficiency virus to be revealed, yet details regarding which proteins are degraded are not fully demonstrated. Recently, host cellular factor CBFβ was found to be essential for Vif to function and promote viral infectivity. In this study, we present more critical information on the Vif-CBFβ interaction by revealing that hydrophobicity contributes the most to the Vif-CBFβ interaction and locating several novel hydrophobic sites (tryptophans and phenylalanines) that are conserved among Vif proteins from different lentiviruses and essential for Vif binding to CBFβ. Mutations on these sites result in a reduced/abolished Vif-CBFβ interaction, leading to the attenuated potency of Vif on both inducing the degradation of antiviral factors like APOBEC3G and promoting HIV-1 infectivity. Therefore, information from this study will help people to further understand how Vif acts against host antiviral mechanism, which is important for novel anti-HIV-1 drug development. [ABSTRACT FROM AUTHOR]

The sterile alpha motif (SAM) and HD domain-containing protein-1 (SAMHD1) inhibits the infection of resting CD4+ T cells and myeloid cells by human and related simian immunodeficiency viruses (HIV and SIV). Vpx inactivates SAMHD1 by promoting its proteasome-dependent degradation through an interaction with CRL4 (DCAF1) E3 ubiquitin ligase and the C-terminal region of SAMHD1. However, the determinants in SAMHD1 that are required for Vpx-mediated degradation have not been well characterized. SAMHD1 contains a classical nuclear localization signal (NLS), and NLS point mutants are cytoplasmic and resistant to Vpx-mediated degradation. Here, we demonstrate that NLS-mutant SAMHD1 K11A can be rescued by wild-type SAMHD1, restoring its nuclear localization; consequently, SAMHD1 K11A became sensitive to Vpx-mediated degradation in the presence of wild-type SAMHD1. Surprisingly, deletion of N-terminal regions of SAMHD1, including the classical NLS, generated mutant SAMHD1 proteins that were again sensitive to Vpx-mediated degradation. Unlike SAMHD1 K11A, these deletion mutants could be detected in the nucleus. Interestingly, NLS-defective SAMHD1 could still bind to karyopherin-β1 and other nuclear proteins. We also determined that the linker region between the SAM and HD domain and the HD domain itself is important for Vpx-mediated degradation but not Vpx interaction. Thus, SAMHD1 contains an additional nuclear targeting mechanism in addition to the classical NLS. Our data indicate that multiple regions in SAMHD1 are critical for Vpx-mediated nuclear degradation and that association with Vpx is not sufficient for Vpx-mediated degradation of SAMHD1. Since the linker region and HD domain may be involved in SAMHD1 multimerization, our results suggest that SAMHD1 multimerization may be required for Vpx-mediation degradation. [ABSTRACT FROM AUTHOR]

Despite concern with turnover in the U.S. House of Representatives, few scholars have attempted to view turnover in historical perspective or in all its forms. Confusion over the basic facts has impeded attempts to explain and evaluate levels of turnover. We present a broad descriptive overview of turnover over the entire history of the U.S. House in terms of the levels of overall turnover, forms thereof, and patterns, particularly within party periods. The findings include that turnover has declined over the years but not in a continuous fashion and not evenly among the different forms, that general election defeat is not the primary form of turnover, that common methods of reporting turnover magnify the apparent importance of electorally based turnover, and that turnover varies systematically by party period. A research agenda is proposed for explanatory work on turnover including strategic retirement and the impact of partisan realignments on levels and forms of turnover. [ABSTRACT FROM AUTHOR]

Purpose: Body composition measures provide valuable information for prognostication and treatment election in cancer patients. We investigated the novel use of magnetic resonance imaging (MRI) for skeletal muscle and adipose tissue cross-sectional area measurements in preoperative renal cell carcinoma (RCC) patients.Materials and Methods: RCC patients with pre-operative CT and MRI abdominal imaging were identified. Semi-automatic segmentation measurement of skeletal muscle area (SMA), intramuscular fat area (IMFA), visceral fat area (VFA), subcutaneous fat area (SFA), linear measurements of psoas, paraspinal muscles were performed. Pearson correlation coefficients, Bland-Altman plot analyses were done. Multivariable regression analysis examined the relationship between patient characteristics and skeletal muscle.Results: Image analysis was performed on 58 RCC patients with preoperative CT and MRI imaging. For segmentation measures, r = 0.99, 0.99, 0.99, and 0.98 for SMA, IMFA, VFA, SFA, respectively, and 0.96 for linear measures of skeletal muscle. Bland-Altman analysis revealed a bias toward larger CT value for SMA (1.35 %), linear muscle measures (2.79 %), and SFA (10.34 %), and toward larger MRI values for IMFA (0.75 %) and VFA (5.81 %). ECOG ≥ 1 was associated with lower skeletal muscle than ECOG 0 for all measurements.Conclusions: Strong correlation of CT and MRI cross sectional measurements of skeletal muscle and adipose tissues supports the use of axial MRI images for comprehensive measurement of body composition. This has widespread implications for body composition research and cancer patient care. [ABSTRACT FROM AUTHOR]