ObjectiveTo characterise individual and area-level risks associated with invasive or skin and soft tissue (SSTIs) Staphylococcus aureus infections comparing methicillin-resistant S. aureus (MRSA) ...with methicillin-sensitive S. aureus (MSSA); and highlight differences between children and adults.SettingA population-based study from 21 reporting laboratories located in Georgia Health District 3 (HD3), an eight-county catchment area around metro Atlanta.ParticipantsA case is a resident of HD3 from whom S. aureus had been isolated in 2017.Primary outcomeCulture-confirmed S. aureus infections, classified as skin and soft tissue (proxy for non-invasive) or invasive, by methicillin-sensitivity status.ResultsThe incidence of SSTIs was 19.7/100 000, compared with 5.2/100 000 for invasive infections. Adults experienced higher rates of SSTIs (22.3/100 000) and invasive infections (6.7/100 000) compared with children with SSTIs (13.0/100 000) and invasive infections (1.3/100 000). Risks of MRSA versus MSSA SSTIs were similar for children and adults. Black individuals with SSTIs were more likely to have MRSA than white individuals (children (OR 1.43, 95% CI 1.16 to 1.76); adults (OR 1.24, 95% CI 1.08 to 1.42)). Adults with invasive MRSA were more likely to be black (adjusted OR 1.69, 95% CI 1.25 to 2.29) compared with those with invasive MSSA. Children with invasive MRSA were more likely from a racial-ethnic concentrated area (OR 4.66, 95% CI 1.85 to 11.71). Hotspots of MRSA were found in crowded areas with higher rates of black populations.ConclusionsThe risk of MRSA infections in children and adults can be defined by unique area-level sociodemographic characteristics which were distinct for those areas associated with MSSA infections. Place-based risks of MRSA or MSSA can be used to develop target public health interventions to decrease transmission and incidence.
The influence of implicit biases in virtual interviews must be addressed to ensure equity within the admissions process. ABATE is a mnemonic framework of five specific categories of implicit bias ...(affinity-based, backdrop-based, appearance-based, technology and media-based, and enunciation-based biases) that should be anticipated and mitigated for faculty, staff, health professionals, and medical students who conduct virtual interviews at medical schools.IntroductionThe influence of implicit biases in virtual interviews must be addressed to ensure equity within the admissions process. ABATE is a mnemonic framework of five specific categories of implicit bias (affinity-based, backdrop-based, appearance-based, technology and media-based, and enunciation-based biases) that should be anticipated and mitigated for faculty, staff, health professionals, and medical students who conduct virtual interviews at medical schools.A 60-minute workshop was developed to educate medical school admissions interviewers about the ABATE model and strategies to mitigate implicit bias during virtual interviews. Four workshops were held over 1 year totaling 217 individual attendees. The workshops were evaluated using a single-group, pre-post questionnaire designed with the Kirkpatrick evaluation model.MethodsA 60-minute workshop was developed to educate medical school admissions interviewers about the ABATE model and strategies to mitigate implicit bias during virtual interviews. Four workshops were held over 1 year totaling 217 individual attendees. The workshops were evaluated using a single-group, pre-post questionnaire designed with the Kirkpatrick evaluation model.Attendees reported that they found the ABATE workshop useful and relevant to improving their ability to minimize implicit bias during virtual interviews. Significant improvements were found in attendee reactions to the utility of implicit bias training (M pre = 2.6, M post = 3.1, p = .002). Significant changes were also reported in attendees' attitudes about interviewing confidence (M pre = 3.0, M post = 3.2, p = .04), bias awareness (M pre = 3.0, M post = 3.4, p = .002), and identifying and applying bias mitigation solutions (M pre = 2.5, M post = 3.0, p = .003). Knowledge specific to backdrop-based biases also significantly increased (M pre = 3.2, M post = 3.4, p = .04).ResultsAttendees reported that they found the ABATE workshop useful and relevant to improving their ability to minimize implicit bias during virtual interviews. Significant improvements were found in attendee reactions to the utility of implicit bias training (M pre = 2.6, M post = 3.1, p = .002). Significant changes were also reported in attendees' attitudes about interviewing confidence (M pre = 3.0, M post = 3.2, p = .04), bias awareness (M pre = 3.0, M post = 3.4, p = .002), and identifying and applying bias mitigation solutions (M pre = 2.5, M post = 3.0, p = .003). Knowledge specific to backdrop-based biases also significantly increased (M pre = 3.2, M post = 3.4, p = .04).The ABATE workshop demonstrates promise in mitigating implicit bias in virtual medical school interviews.DiscussionThe ABATE workshop demonstrates promise in mitigating implicit bias in virtual medical school interviews.
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Inhibition of Rho kinase (ROCK) to improve fluid outflow through the trabecular meshwork and lower intraocular pressure is a strategy for the development of new anti-glaucoma agents. ...Alpha-aryl-beta-amino isoquinoline analogs were identified as potent ROCK inhibitors. Compounds that provided a longer duration of intraocular pressure reduction in Dutch Belted rabbits also inhibited norepinephrine transporter. Ester 60 improved bioavailability of its parent ROCK inhibitor, 29 (Ki=0.2nM) and demonstrated an effective and sustained IOP reduction for 24h after dosing. From these studies, netarsudil (a.k.a. AR-13324) was discovered and is currently in clinical trials for the treatment of glaucoma and ocular hypertension.
Background
Self-monitoring (SM) is the centerpiece of behavioral weight loss treatment, but the efficacy of smartphone-delivered SM feedback (FB) has not been tested in large, long-term, randomized ...trials.
Objective
The aim of this study was to establish the efficacy of providing remote FB to diet, physical activity (PA), and weight SM on improving weight loss outcomes when comparing the SM plus FB (SM+FB) condition to the SM-only condition in a 12-month randomized controlled trial. The study was a single-site, population-based trial that took place in southwestern Pennsylvania, USA, conducted between 2018 and 2021. Participants were smartphone users age ≥18 years, able to engage in moderate PA, with a mean BMI between 27 and 43 kg/m2.
Methods
All participants received a 90-minute, one-to-one, in-person behavioral weight loss counseling session addressing behavioral strategies, establishing participants’ dietary and PA goals, and instructing on use of the PA tracker (Fitbit Charge 2), smart scale, and diet SM app. Only SM+FB participants had access to an investigator-developed smartphone app that read SM data, in which an algorithm selected tailored messages sent to the smartphone up to 3 times daily. The SM-only participants did not receive any tailored FB based on SM data. The primary outcome was percent weight change from baseline to 12 months. Secondary outcomes included engagement with digital tools (eg, monthly percentage of FB messages opened and monthly percentage of days adherent to the calorie goal).
Results
Participants (N=502) were on average 45.0 (SD 14.4) years old with a mean BMI of 33.7 (SD 4.0) kg/m2. The sample was 79.5% female (n=399/502) and 82.5% White (n=414/502). At 12 months, retention was 78.5% (n=394/502) and similar by group (SM+FB: 202/251, 80.5%; SM: 192/251, 76.5%; P=.28). There was significant percent weight loss from baseline in both groups (SM+FB: –2.12%, 95% CI –3.04% to –1.21%, P<.001; SM: –2.39%, 95% CI –3.32% to –1.47%; P<.001), but no difference between the groups (–0.27%; 95% CI –1.57% to 1.03%; t =–0.41; P=.68). Similarly, 26.3% (66/251) of the SM+FB group and 29.1% (73/251) of the SM group achieved ≥5% weight loss (chi-square value=0.49; P=.49). A 1% increase in FB messages opened was associated with a 0.10 greater percent weight loss at 12 months (b=–0.10; 95% CI –0.13 to –0.07; t =–5.90; P<.001). A 1% increase in FB messages opened was associated with 0.12 greater percentage of days adherent to the calorie goal per month (b=0.12; 95% CI 0.07-0.17; F=22.19; P<.001).
Conclusions
There were no significant between-group differences in weight loss; however, the findings suggested that the use of commercially available digital SM tools with or without FB resulted in a clinically significant weight loss in over 25% of participants. Future studies need to test additional strategies that will promote greater engagement with digital tools.
Trial Registration
Clinicaltrials.gov NCT03367936; https://clinicaltrials.gov/ct2/show/NCT03367936
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Giant cell-rich lesions of bone represent a heterogeneous group of entities which classically include giant cell tumor of bone, aneurysmal bone cyst, nonossifying fibroma, and Brown tumor of ...hyperparathyroidism. A recently described subset of giant cell-rich tumors involving bone and soft tissue has been characterized by recurrent HMGA2::NCOR2 fusions and keratin expression. The overlapping clinical, radiographic, and morphological features of these giant cell-rich lesions provide a unique diagnostic challenge, particularly on biopsy. We present 2 additional cases of keratin-positive giant cell-rich tumor of bone with HMGA2::NCOR2 fusions, including 1 patient who developed metastatic disease.
Experimental data about gene functions curated from the primary literature have enormous value for research scientists in understanding biology. Using the Gene Ontology (GO), manual curation by ...experts has provided an important resource for studying gene function, especially within model organisms. Unprecedented expansion of the scientific literature and validation of the predicted proteins have increased both data value and the challenges of keeping pace. Capturing literature-based functional annotations is limited by the ability of biocurators to handle the massive and rapidly growing scientific literature. Within the community-oriented wiki framework for GO annotation called the Gene Ontology Normal Usage Tracking System (GONUTS), we describe an approach to expand biocuration through crowdsourcing with undergraduates. This multiplies the number of high-quality annotations in international databases, enriches our coverage of the literature on normal gene function, and pushes the field in new directions. From an intercollegiate competition judged by experienced biocurators, Community Assessment of Community Annotation with Ontologies (CACAO), we have contributed nearly 5,000 literature-based annotations. Many of those annotations are to organisms not currently well-represented within GO. Over a 10-year history, our community contributors have spurred changes to the ontology not traditionally covered by professional biocurators. The CACAO principle of relying on community members to participate in and shape the future of biocuration in GO is a powerful and scalable model used to promote the scientific enterprise. It also provides undergraduate students with a unique and enriching introduction to critical reading of primary literature and acquisition of marketable skills.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Immunoediting sculpts immunogenicity and thwarts host anti-tumor responses in tumor cells during tumorigenesis; however, it remains unknown whether metabolic programming of tumor cells can be guided ...by immunosurveillance. Here, we report that T cell-mediated immunosurveillance in early-stage tumorigenesis instructs c-Myc upregulation and metabolic reprogramming in tumor cells. This previously unexplored tumor-immune interaction is controlled by non-canonical interferon gamma (IFNγ)-STAT3 signaling and supports tumor immune evasion. Our findings uncover that immunoediting instructs deregulated bioenergetic programs in tumor cells to empower them to disarm the T cell-mediated immunosurveillance by imposing metabolic tug-of-war between tumor and infiltrating T cells and forming the suppressive tumor microenvironment.
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•Immunometabolic editing orchestrates metabolic preferences in tumor cells•Metabolic program acquired by edited tumor cells supports tumor immune evasion•IFNγ-driven editing modulates cMyc expression in a non-canonical STAT3 pathway•Immunosurveillance impacts tumor epigenetic program for boosting aggressiveness
Metabolic reprogramming, generally believed to be controlled by oncogenic mutations and hypoxia, supports tumor proliferation, anti-apoptosis, and metastasis. Here, we uncover an unexplored action of IFNγ by which T cell-mediated immunosurveillance impacts epigenetic architecture and gene expression in tumor cells that boosts cMyc-dependent metabolic reprogramming and tumor immune evasion.
In the few weight loss studies assessing diet quality, improvements have been minimal and recommended calculation methods have not been used. This secondary analysis of a parallel group randomised ...trial (regsitered: https://clinicaltrials.gov/ct2/show/NCT03367936) assessed whether self-monitoring with feedback (SM + FB) v. self-monitoring alone (SM) improved diet quality. Adults with overweight/obesity (randomised: SM n 251, SM + FB n 251; analysed SM n 170, SM + FB n 186) self-monitored diet, physical activity and weight. Real-time, personalised feedback, delivered via a study-specific app up to three times daily, was based on reported energy, fat and added sugar intake. Healthy Eating Index 2015 (HEI-2015) scores were calculated from 24-hour recalls. Higher scores represent better diet quality. Data were collected August 2018 to March 2021 and analysed spring 2022. The sample was mostly female (78·9 %) and white (85·4 %). At baseline, HEI-2015 total scores and bootstrapped 95 % CI were similar by treatment group (SM + FB: 63·11 (60·41, 65·24); SM: 61·02 (58·72, 62·81)) with similar minimal improvement observed at 6 months (SM + FB: 65·42 (63·30, 67·20); SM: 63·19 (61·22, 64·97)) and 12 months (SM + FB: 63·94 (61·40, 66·29); SM: 63·56 (60·81, 65·42)). Among those who lost ≥ 5 % of baseline weight, HEI-2015 scores improved (baseline: 62·00 (58·94, 64·12); 6 months: 68·02 (65·41, 71·23); 12 months: 65·93 (63·40, 68·61)). There was no effect of the intervention on diet quality change. Clinically meaningful weight loss was related to diet quality improvement. Feedback may need to incorporate more targeted nutritional content.
Conjoint Behavioral Consultation (CBC) is an evidence-based, indirect service delivery model that addresses children's behavioral concerns across home and school. However, to date, researchers have ...not yet examined specific aspects of the intervention that maximize the effects of CBC. The current study examined whether a foundational aspect of consultation-the framing of target behaviors (i.e., positive behaviors to increase versus negative behaviors to decrease)-moderated the effects of CBC on children's problem and adaptive behaviors. Participants were 267 children in Kindergarten through third grade (n
CBC
= 159, n
Control
= 108) and their parents and teachers. Results revealed positively framed target behaviors were associated with fewer behavior concerns at school for children who received CBC relative to other child participants. Children who received CBC and whose target behaviors were framed negatively showed more noncompliant behavior relative to all other participants. Implications of these findings for practice, study limitations, and areas for future research are discussed.
Impact Statement
In the absence of effective intervention, students with behavioral challenges face a lifetime of difficulty. Ample research documents the efficacy of conjoint behavioral consultation (CBC) for promoting prosocial behaviors and ameliorating school difficulties. This study demonstrates that the effects of CBC can be amplified by intentionally framing target behaviors in a positive (i.e., desirable behaviors to improve) versus negative (i.e., undesirable behaviors to decrease) manner, providing a simple but significant method for improving practice.
Problem:
Academic medical centers need to mitigate the negative effects of implicit bias with approaches that are empirically-based, scalable, sustainable, and specific to departmental needs. Guided ...by Kotter's Model of Change to create and sustain cultural change, we developed the Bias Reduction Improvement Coaching Program (BRIC), a two-year, train-the-trainer implicit bias coaching program designed to meet the increasing demand for bias training across a university medical center.
Intervention:
BRIC trained a cohort of faculty and staff as coaches during four quarterly training sessions in Year 1 that covered 1) the science of bias, 2) bias in selection and hiring, 3) bias in mentoring, and 4) bias in promotion, retention, and workplace culture. In Year 2, coaches attended two booster sessions and delivered at least two presentations. BRIC raises awareness of bias mitigation strategies in a scalable way by uniquely building capacity through department-level champions, providing programming that addresses the 'local context,' and setting a foundation for sustained institutional change.
Context:
In a U.S. academic medical center, 27 faculty and staff from 24 departments were trained as inaugural BRIC coaches. We assessed outcomes at multiple levels: BRIC coach outcomes (feedback on the training sessions; coach knowledge, attitudes, and skills), departmental-level outcomes (program attendee feedback, knowledge, and intentions) and institutional outcomes (activities to sustain change).
Impact:
After Year 1, coaches reported high satisfaction with BRIC and a statistically significant increase in self-efficacy in their abilities to recognize, mitigate, and teach about implicit bias. In Year 2, attendees at BRIC coach presentations reported an increase in bias mitigation knowledge, and the majority committed to taking follow-up action (e.g., taking an Implicit Association Test). Coaches also launched activities for sustaining change at the broader university and beyond.
Lessons Learned:
The BRIC Program indicates a high level of interest in receiving bias mitigation training, both among individuals who applied to be BRIC coaches and among presentation attendees. BRIC's initial success supports future expansion. The model appears scalable and sustainable; future efforts will formalize the emerging community of practice around bias mitigation and measure elements of on-going institutional culture change.
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