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Abstract Background The gut microbiota contributes to macrophage-mediated inflammation in adipose tissue with consumption of an obesogenic diet, thus driving the development of metabolic syndrome. There is a need to identify and develop interventions that abrogate this condition. The hops-derived prenylated flavonoid xanthohumol (XN) and its semi-synthetic derivative tetrahydroxanthohumol (TXN) attenuate high-fat diet-induced obesity, hepatosteatosis, and metabolic syndrome in C57Bl/6J mice. This coincides with a decrease in pro-inflammatory gene expression in the gut and adipose tissue, together with alterations in the gut microbiota and bile acid composition. Results In this study, we integrated and interrogated multi-omics data from different organs with fecal 16S rRNA sequences and systemic metabolic phenotypic data using a Transkingdom Network Analysis. By incorporating cell type information from single-cell RNA-seq data, we discovered TXN attenuates macrophage inflammatory processes in adipose tissue. TXN treatment also reduced levels of inflammation-inducing microbes, such as Oscillibacter valericigenes, that lead to adverse metabolic phenotypes. Furthermore, in vitro validation in macrophage cell lines and in vivo mouse supplementation showed addition of O. valericigenes supernatant induced the expression of metabolic macrophage signature genes that are downregulated by TXN in vivo. Conclusions Our findings establish an important mechanism by which TXN mitigates adverse phenotypic outcomes of diet-induced obesity and metabolic syndrome. TXN primarily reduces the abundance of pro-inflammatory gut microbes that can otherwise promote macrophage-associated inflammation in white adipose tissue. Video Abstract

Deafblindness is complex, and there is very limited research on literacy for learners who are deafblind, including on comprehension. This study investigated current practices for comprehension development for learners who are deafblind. Data were collected through a survey and interviews from 63 U.S. participants who were teachers, interveners, and parents. Thematic analysis resulted in the emergence of themes and strategies related to supporting and measuring comprehension during shared reading for learners who are deafblind. Strategies for supporting comprehension include multiple communication forms, customizing the text, repeating, exploring materials, and integrating technology. For measuring comprehension strategies include questioning, completing phrases, commenting and discussing, retelling, sequencing, and extension activities. Implications for research include future investigations on the effectiveness of the strategies currently reported to support and measure comprehension. Implications for practice include developing understanding by supporting communication and access during shared reading while using multiple measures of comprehension.

Introduction: Shared reading has shown the ability to enrich language development in children (Dowdall et al., 2020) and academic skills into adulthood (Mol & Bus, 2011). However, due to the complexities of deafblindness and its effect on communication, some individuals may not be able to participate in traditional shared reading. Although there is very limited research on literacy for learners who are deafblind (Bruce et al., 2016), with appropriate materials and supports within the immediate environment, shared reading has the potential to be a vehicle to support literacy and communication development for learners who are deafblind. Methods: A mixed methods online survey (n = 60) and follow-up interviews (n = 10) helped to explore how parents, teachers, and interveners curated materials and structured the learning environment for shared reading. Descriptive statistics and inductive analysis were applied to analyze quantitative and qualitative information. Results: Information on how materials (e.g., type, selection, and adaptations) and the learning environment (e.g., location of the activity, learner positioning, and instructional supports) were utilized to support learners who are deafblind during shared reading is presented. Considerations for materials selection and development included access needs (vision, hearing, tactile), communication abilities, interests, and previous experiences. The learning environment was often intentionally selected or designed with considerations for lighting, noise, and distractions. Discussion: Materials were individualized and personalized, with supplementary items added to support communication and comprehension of the text. Learning environments were literacy-rich and accessible to the learner. Future intervention research is needed on shared reading for learners who are deafblind. Conclusion: Because of the nature of deafblindness, careful planning and implementation are needed when designing materials and learning environments for engaging learners in literacy. Future intervention research is needed to demonstrate the effective implementation of individualized and personalized literacy materials and identify environmental considerations for learners who are deafblind.

In this article, a two-year partnership aims to disrupt inequities in curriculum and instruction by supporting teachers' efforts to better teach American Indian studies. The authors focus on the foundations of the partnership and how they implemented their professional learning, as well as important lessons about facilitating teacher professional learning.

This study was performed to assess the seroprevalence against Japanese encephalitis virus (JEV) in chickens collected from an urban area of Denpasar and a rural area of Karangasem in Bali. A total of 142 domestic chickens were sampled and then tested using enzyme linked immunosorbent assay (ELISA) to detect the antibodies. The seroprevalence was calculated in each of the clustered areas and the seropositivity was associated with age and sex of the sampled chickens. The results showed that chickens collected in Denpasar had 97.10% (n=70, 95% CI: 90.8899.52) seroprevalence against JEV, whereas the chickens collected from Karangasem Regency had a seroprevalence of 93.05% (n=72, 95% CI: 85.2897.41). In association with area collection, age and sex, chickens collected from Denpasar were 2.5 times (OR: 2.5, 95% CI: 0.4813.53, P>0.05) more likely to be seropositive containing the antibodies against JEV compared to the chickens from Karangasem Regency. Mean-while, chickens of age equal to or more than six months were 6.2 times (OR: 6.2, 95% CI: 1.1533.07, P0.05) more likely to be seropositive compared to females. No significant difference was observed for the seroprevalence in the chickens collected in both areas even though it was found to be significantly associated with the chickens’ age.

Exercise is a powerful tool for disease prevention and rehabilitation. Commercially available virtual reality (VR) devices and apps offer an immersive platform to gamify exercise and potentially enhance physiological and psychological benefits. However, no work has compared immersive exercise to closely matched 2D screen-based equivalents with the same visual and auditory stimuli. This study aims to compare the acute effects of an exercise session using a commercial immersive VR workout to the same stimuli and workout presented on a screen. 17 healthy participants (male = 7, female = 10; aged 24.18±4.56 years), completed a 12-minute guided VR boxing exercise session in FitXR™ and a screen-based equivalent. Physiological responses were recorded continuously using a heart rate monitor and telemetricmetabolic cart system. Psychological and perceptual responses were measured using their ratings of perceived exertion, the physical activity enjoyment scale, and the physical activity affect scale. In the immersive VR participants chose to engage in more intense exercise (%VO2max; p = 0.044), showed higher levels of all enjoyment subscales (p

Weight loss interventions seldom include individuals with neurologic disease. The aims of the present study were to: 1) develop and assess the prefeasibility of a 6-month telehealth behavioral weight loss program for people with multiple sclerosis (MS) and obesity and 2) examine changes in weight loss (primary outcome), physical activity, and fruit/vegetable consumption at follow-up. Participants with obesity and MS engaged in a 24-week weight loss program. Participants followed established diet, exercise, and self-monitoring guidelines and attended weekly online group meetings. Median percentage weight loss was 10.54 % (SD = 7.19). Participants who adhered more closely to the self-monitoring guidelines (r = 0.81, p =.02), and who averaged higher weekly active minutes (r = 0.91, p =.002) achieved greater percentage weight loss. Six of the eight pilot participants achieved clinically meaningful weight loss (>5%) after 6-months.

Summary: Background: Depression is three to four times more prevalent in patients with neurological and inflammatory disorders than in the general population. For example, in patients with multiple sclerosis, the 12-month prevalence of major depressive disorder is around 25% and it is associated with a lower quality of life, faster disease progression, and higher morbidity and mortality. Despite its clinical relevance, there are few treatment options for depression associated with multiple sclerosis and confirmatory trials are scarce. We aimed to evaluate the safety and efficacy of a multiple sclerosis-specific, internet-based cognitive behavioural therapy (iCBT) programme for the treatment of depressive symptoms associated with the disease. Methods: This parallel-group, randomised, controlled, phase 3 trial of an iCBT programme to reduce depressive symptoms in patients with multiple sclerosis was carried out at five academic centres with large outpatient care units in Germany and the USA. Patients with a neurologist-confirmed diagnosis of multiple sclerosis and depressive symptoms were randomly assigned (1:1:1; automated assignment, concealed allocation, no stratification, no blocking) to receive treatment as usual plus one of two versions of the iCBT programme Amiria (stand-alone or therapist-guided) or to a control condition, in which participants received treatment as usual and were offered access to the iCBT programme after 6 months. Masking of participants to group assignment between active treatment and control was not possible, although raters were masked to group assignment. The predefined primary endpoint, which was analysed in the intention-to-treat population, was severity of depressive symptoms as measured by the Beck Depression Inventory-II (BDI-II) at week 12 after randomisation. This trial is registered at ClinicalTrials.gov, NCT02740361, and is complete. Findings: Between May 3, 2017, and Nov 4, 2020, we screened 485 patients for eligibility. 279 participants were enrolled, of whom 101 were allocated to receive stand-alone iCBT, 85 to receive guided iCBT, and 93 to the control condition. The dropout rate at week 12 was 18% (50 participants). Both versions of the iCBT programme significantly reduced depressive symptoms compared with the control group (BDI-II between-group mean differences: control vs stand-alone iCBT 6·32 points [95% CI 3·37–9·27], p

Context. Intact male (ram) lambs are often discounted by meat processors because of their perceived defective meat quality. Aims. This study quantified the effects of castration on the liveweight, growth, carcass parameters and the meat quality of male lambs. Methods. Liveweight, growth and carcass data were collected from 133 ram and 132 castrated (wether) lambs reared under a pasture-fed production system. A total of 50 lambs were subsequently selected, balanced by final curfew liveweight and castration status, to investigate additional carcass, meat quality, consumer sensory panel scores and colour stability parameters. Key results. It was found that total average daily gains for ram lambs were highest (242.9 ± 5.2 g/day; P = 0.002), resulting from their higher preweaning growth rate of 327.7 ± 9.7 g/day (P < 0.001). Wethers were fattier, having higher estimated intramuscular fat (3.9 vs 3.3 ± 0.1%, respectively) and subcutaneous fat depth (14.7 vs 13.5 ± 0.4 mm, respectively) than ram lambs. Purge loss (P < 0.030) and ultimate pH (P < 0.035) were higher for the meat of wether lambs, but only after 32 days of wet ageing. Consumers scored the meat of wether lambs as significantly more tender (61.0 vs 54.6 ± 2.3%; P = 0.005) and of greater overall liking (65.1 vs 61.1 ± 2.0%; P = 0.044) than that of ram lambs. These, and a comparison of shear force, near infrared spectroscopy for intramuscular fat content and retail colour with consumer thresholds, suggest a general satisfaction with ram and wether lamb meat quality. Conclusions. Collectively, there seems to be few tangible performance and meat quality advantages to the castration of male lambs. Implications. Prime lamb producers must consider flock management and market preference when deciding on best practice. [ABSTRACT FROM AUTHOR]

Teacher leadership development receives considerable attention in many educational reforms across the globe. This article reports on a unique partnership in Jerusalem that brings Israeli and Palestinian educators together to cultivate teacher leaders who facilitate professional communities and support continual improvement in teaching and learning. The research design involves participatory action research and draws on theoretical frameworks of democratic education, productive professional discourse, and authentic intellectual work. Findings focus on the enhancement of multicultural training, increased depth of pedagogical discussions, and improvement in leading teacher learning communities. The conclusions consider the ways in which a few bridges are overcoming both real and perceived borders in a region of persisting cultural tension and conflict, as the teacher leaders and co-authors developed an emerging common understanding of a shared conception of professional practice across three languages, and a growing mutual respect for the 'other'.

Sky Shepherding is a concept whereby moving tasks are performed by an autonomous airborne agent capable of responding to animal behaviour and improving animal welfare outcomes. To achieve this outcome, a series of experiments investigated the potential welfare impacts of using a purpose-built Sky Shepherd compared to a trained sheepdog. Data was collected using a bespoke system of mobile phones, heart-rate sensors, and edge computing devices. In this article, we present the findings of the experiments, specifically that a Sky Shepherd has the potential to foster improved animal welfare on farms but does not significantly reduce the physiological stress of Merino sheep during mustering. We outline the system requirements developed to build a Sky Shepherd and supporting sensor network and the future directions to support improved performance. Finally, we present the potential challenges to using high data-rate transfer systems in remote areas and possible future mitigations to support autonomous muster capabilities.

Objective Although individual-level social determinants of health (SDH) are known to influence 30-day readmission risk, contextual-level associations with readmission are poorly understood among children. This study explores associations between neighborhood disadvantage measured by Area Deprivation Index (ADI) and pediatric 30-day readmissions. Methods This retrospective cohort study included discharges of patients aged < 20 years from Maryland's 2013-2016 all-payer dataset. The ADI, which quantifies 17 indicators of neighborhood socioeconomic disadvantage within census block groups, is used as a proxy for contextual-level SDH. Readmissions were identified with the 30-day Pediatric All-Condition Readmissions measure. Associations between ADI and readmission were identified with generalized estimating equations adjusted for patient demographics and clinical severity (Chronic Condition Indicator [CCI], Pediatric Medical Complexity Algorithm [PMCA], Index Hospital All Patients Refined Diagnosis Related Groups [APR-DRG]), and hospital discharge volume. Results Discharges (n = 138,998) were mostly female (52.7%), publicly insured (55.1%), urban-dwelling (93.0%), with low clinical severity levels (0-1 CCIs [82.3%], minor APR-DRG severity [48.4%]). Overall readmission rate was 4.0%. Compared to the least disadvantaged ADI quartile, readmissions for the most disadvantaged quartile were significantly more likely (aOR 1.19, 95% CI 1.09-1.30). After adjustment, readmissions were associated with public insurance and indicators of medical complexity (higher number of CCIs, complex-chronic disease PMCA, and APR-DRG severity). Conclusion In this all-payer, statewide sample, living in the most socioeconomically disadvantaged neighborhoods independently predicted pediatric readmission. While the relative magnitude of neighborhood disadvantage was modest compared to medical complexity, disadvantage is modifiable and thus represents an important consideration for prevention and risk stratification efforts., Author(s): Carrie L. Nacht [sup.1] , Michelle M. Kelly [sup.1] , M. Bruce Edmonson [sup.1] , Daniel J. Sklansky [sup.1] , Kristin A. Shadman [sup.1] , Amy J. H. Kind [...]

Contracting delays remain a challenge to the successful initiation of multisite clinical research in the US. The Clinical and Translational Science Awards (CTSA) Contracts Processing Study showed average contract negotiation duration of > 100 days for industry-sponsored or investigator-initiated contracts. Such delays create enormous costs to sponsors and to patients waiting to use new evidence-based treatments. With support from the National Institutes of Health’s National Center for Advancing Translational Sciences, the Accelerated Clinical Trial Agreement (ACTA) was developed by 25 major academic institutions and medical centers engaged in clinical research in collaboration with the University-Industry Demonstration Partnership and with input from pharmaceutical companies. The ACTA also informed the development of subsequent agreements, including the Federal Demonstration Partnership Clinical Trial Subaward Agreement (FDP-CTSA); both ACTA and the FDP-CTSA are largely non-negotiable agreements that represent pre-negotiated compromises in contract terms agreed upon by industry and/or medical center stakeholders. When the involved parties agree to use the CTSA-developed and supported standard agreement templates as a starting point for negotiations, there can be significant time savings for trials. Use of the ACTA resulted in an average savings of 48 days and use of the FDP-CTSA saved an average of 57 days of negotiation duration.

Electromagnetic field (EMF) theories of mind/brain integration have been proposed to explain brain function for over seventy years. Interest in this theory continues to this day because it explains mind-brain integration and it offers a simple solution to the “binding problem” of our unified conscious experience. Thus, it addresses at least in part the “hard problem” of consciousness. EMFs are easily measured and many corelates have been noted for field activity; associated with loss and recovery of consciousness, sensory perceptions, and behavior. Unfortunately, the theory was challenged early on by experiments that were thought to have ruled out a role of EMFs in brain activity, and the field of neuroscience has since marginalized EMF theories. Here I explain why early evidence against EMFs contributing to consciousness was misinterpreted and offer an alternative view to help direct future research.

While geriatric patients have a high likelihood of requiring anesthesia, they carry an increased risk for adverse cognitive outcomes from its use. Previous work suggests this could be mitigated by better intraoperative monitoring using indexes defined by several processed electroencephalogram (EEG) measures. Unfortunately, inconsistencies between patients and anesthetic agents in current analysis techniques have limited the adoption of EEG as standard of care. In attempts to identify new analyses that discriminate clinically-relevant anesthesia timepoints, we tested 1/f frequency scaling as well as measures of complexity from nonlinear dynamics. Specifically, we tested whether analyses that characterize time-delayed embeddings, correlation dimension (CD), phase-space geometric analysis, and multiscale entropy (MSE) capture loss-of-consciousness changes in EEG activity. We performed these analyses on EEG activity collected from a traditionally hard-to-monitor patient population: geriatric patients on beta-adrenergic blockade who were anesthetized using a combination of fentanyl and propofol. We compared these analyses to traditional frequency-derived measures to test how well they discriminated EEG states before and after loss of response to verbal stimuli. We found spectral changes similar to those reported previously during loss of response. We also found significant changes in 1/f frequency scaling. Additionally, we found that our phase-space geometric characterization of time-delayed embeddings showed significant differences before and after loss of response, as did measures of MSE. Our results suggest that our new spectral and complexity measures are capable of capturing subtle differences in EEG activity with anesthesia administration-differences which future work may reveal to improve geriatric patient monitoring.

Abstract Extracorporeal membrane oxygenation (ECMO) support has a high incidence of both bleeding and thrombotic complications. Despite clear differences in patient characteristics and pathologies between veno-venous (VV) and veno-arterial (VA) ECMO support, anticoagulation practices are often the same across modalities. Moreover, there is very little data on their respective coagulation profiles and comparisons of thrombin generation in these patients. This study compares the coagulation profile and thrombin generation between patients supported with either VV and VA ECMO. A prospective cohort study of patients undergoing VA and VV ECMO at an Intensive care department of a university hospital and ECMO referral centre. In addition to routine coagulation testing and heparin monitoring per unit protocol, thromboelastography (TEG), multiplate aggregometry (MEA), calibrated automated thrombinography (CAT) and von-Willebrand’s activity (antigen and activity ratio) were sampled second-daily for 1 week, then weekly thereafter. VA patients had significantly lower platelets counts, fibrinogen, anti-thrombin and clot strength with higher d-dimer levels than VV patients, consistent with a more pronounced consumptive coagulopathy. Thrombin generation was higher in VA than VV patients, and the heparin dose required to suppress thrombin generation was lower in VA patients. There were no significant differences in total bleeding or thrombotic event rates between VV and VA patients when adjusted for days on extracorporeal support. VA patients received a lower median daily heparin dose 8500 IU [IQR 2500–24000] versus VV 28,800 IU [IQR 17,300–40,800.00];

Objectives: Children with medical complexity experienced health disparities during the coronavirus disease 2019 (COVID-19) pandemic. Language may compound these disparities since people speaking languages other than English (LOE) also experienced worse COVID-19 outcomes. Our objective was to investigate associations between household language for children with medical complexity and caregiver COVID-19 vaccine intentions, testing knowledge, and trusted sources of information. Methods: This cross-sectional survey of caregivers of children with medical complexity ages 5 to 17 years was conducted from April-June 2022. Children with medical complexity had at least 1 Complex Chronic Condition. Households were considered LOE if they reported speaking any language other than English. Multivariable logistic regression examined associations between LOE and COVID-19 vaccine intentions, interpretation of COVID-19 test results, and trusted sources of information. Results: We included 1,338 caregivers of children with medical complexity (49% response rate), of which 133 (10%) had household LOE (31 total languages, 58% being Spanish). There was no association between household LOE and caregiver COVID-19 vaccine intentions. Caregivers in households with LOE had similar interpretations of positive COVID-19 test results, but significantly different interpretations of negative results. Odds of interpreting a negative test as expected (meaning the child does not have COVID-19 now or can still get the virus from others) were lower in LOE households (aOR [95% CI]: 0.56 [0.34–0.95]). Households with LOE were more likely to report trusting the US government to provide COVID-19 information (aOR [95% CI]: 1.86 [1.24–2.81]). Conclusion: Differences in COVID-19 test interpretations based on household language for children with medical complexity were observed and could contribute to disparities in outcomes. Opportunities for more inclusive public health messaging likely exist. [ABSTRACT FROM AUTHOR]

PurposeTo compare fibrosis, aqueous humor dynamics, and intraocular pressure (IOP) of two suprachoroidal shunts as part of a new class of glaucoma drainage devices.MethodsFollowing proliferation analysis in vitro, 20 rabbits were implanted with either a gold shunt (GS, GMSplus+, SOLX) or a polypropylene shunt (PS, Aquashunt, OPKO). Ten eyes received mitomycin C (MMC) and triamcinolone. Peak and trough IOP were monitored with a pneumatonometer and tono-pen for 15 weeks. Aqueous humor dynamics were evaluated fluorophotometrically and tonographically. Fibrosis was quantified.ResultsIn vitro proliferation was similar. In vivo, both shunts were devoid of foreign body reaction but exhibited fibrosis, and GS showed vascularization. There was no significant difference in aqueous or uveoscleral flow. Preoperative morning IOP was 23.7 ± 2 mm Hg, and evening IOP was 26.5 ± 2 mm Hg (P = 0.000). Morning IOP was decreased through 15 weeks and evening IOP through 8 weeks in all groups. The morning IOP decrease was most profound at 15 weeks in PS (41%) compared to GS (18%). Antifibrotics initially enhanced but eventually diminished shunt performance. At 15 weeks, thickness of scleral fibrosis was greater in GS (246 ± 47 μm) and PS (188 ± 47 μm, P = 0.285) compared with GS+MMC (109 ± 26 μm, P = 0.023 to GS) and PS+MMC (48 ± 30 μm, P = 0.028 to PS).ConclusionsIn a rabbit model, suprachoroidal polypropylene and gold shunts allow access to a new drainage pathway with different IOP profiles that can be modified with antifibrotics.