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1.
Nat Commun ; 15(1): 2769, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38553486

ABSTRACT

Multiple neurological disorders are associated with gastrointestinal (GI) symptoms, including autism spectrum disorder (ASD). However, it is unclear whether GI distress itself can modify aspects of behavior. Here, we show that mice that experience repeated colitis have impaired active social engagement, as measured by interactions with a foreign mouse, even though signs of colitis were no longer present. We then tested the hypothesis that individuals with ASD harbor a microbiota that might differentially influence GI health by performing microbiota transplantation studies into male germfree animals, followed by induction of colitis. Animals that harbor a microbiota from ASD individuals have worsened gut phenotypes when compared to animals colonized with microbiotas from familial neurotypical (NT) controls. We identify the enrichment of Blautia species in all familial NT controls and observe an association between elevated abundance of Bacteroides uniformis and reductions in intestinal injury. Oral treatment with either of these microbes reduces colon injury in mice. Finally, provision of a Blautia isolate from a NT control ameliorates gut injury-associated active social engagement in mice. Collectively, our data demonstrate that past intestinal distress is associated with changes in active social behavior in mice that can be ameliorated by supplementation of members of the human microbiota.


Subject(s)
Autism Spectrum Disorder , Colitis , Gastrointestinal Diseases , Microbiota , Humans , Male , Mice , Animals , Autism Spectrum Disorder/therapy , Social Participation , Colitis/therapy , Dietary Supplements
2.
Magn Reson Imaging ; 109: 271-285, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38537891

ABSTRACT

Functional magnetic resonance imaging (fMRI) plays a crucial role in neuroimaging, enabling the exploration of brain activity through complex-valued signals. These signals, composed of magnitude and phase, offer a rich source of information for understanding brain functions. Traditional fMRI analyses have largely focused on magnitude information, often overlooking the potential insights offered by phase data. In this paper, we propose a novel fully Bayesian model designed for analyzing single-subject complex-valued fMRI (cv-fMRI) data. Our model, which we refer to as the CV-M&P model, is distinctive in its comprehensive utilization of both magnitude and phase information in fMRI signals, allowing for independent prediction of different types of activation maps. We incorporate Gaussian Markov random fields (GMRFs) to capture spatial correlations within the data, and employ image partitioning and parallel computation to enhance computational efficiency. Our model is rigorously tested through simulation studies, and then applied to a real dataset from a unilateral finger-tapping experiment. The results demonstrate the model's effectiveness in accurately identifying brain regions activated in response to specific tasks, distinguishing between magnitude and phase activation.


Subject(s)
Brain , Magnetic Resonance Imaging , Bayes Theorem , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Brain/physiology , Brain Mapping/methods , Computer Simulation
3.
Des Monomers Polym ; 27(1): 1-9, 2024.
Article in English | MEDLINE | ID: mdl-38344117

ABSTRACT

The thermoresponsive properties of poloxamine (tetra-branch PEO-PPO block copolymer) hydrogels are related to several variables. Of particular interest to this study were the molecular weight of the polymer, the molar ratio between PEO and PPO blocks, and the concentration of the aqueous solution. Accurately controlling the thermoresponsive behaviors of the polymer is critical to the application of such materials; therefore, the structure-property relationship of tetra-branch PEO-PPO block copolymer was studied by synthesis via anionic ring-opening polymerization (AROP). The structure-property relationships were studied by measuring the thermoresponsive behavior via differential scanning calorimetry (DSC) and developing an empirical model which statistically fit the collected data. This empirical model was then used for designing poloxamines that have critical micellization temperatures (CMT) between room temperature and physiological temperature. The model was validated with three polymers that targeted a CMT of 308 K (35°C). The empirical model showed great success in guiding the synthesis of poloxamines showing a temperature difference of less than 3 K between the predicted and the observed CMTs. This study showed a great potential of using an empirical model to set synthesis parameters to control the properties of the polymer products.

4.
Sleep Med ; 114: 145-150, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38183805

ABSTRACT

INTRODUCTION: Obstructive sleep apnea (OSA) is common but under-recognized after stroke. The aim of this study was to determine whether post-stroke phenotypic OSA subtypes are associated with stroke outcome in a population-based observational cohort. METHODS: Ischemic stroke patients (n = 804) diagnosed with OSA (respiratory event index ≥10) soon after ischemic stroke were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) project. Functional, cognitive, and quality of life outcomes were assessed at 90 days post-stroke and long-term stroke recurrence was ascertained. Latent profile analysis was performed based on demographic and clinical features, pre-stroke sleep characteristics, OSA severity, and vascular risk factors. Regression models were used to assess the association between phenotypic clusters and outcomes. RESULTS: Four distinct phenotypic clusters provided the best fit. Cluster 1 was characterized by more severe stroke; cluster 2 by severe OSA and higher prevalence of medical comorbidities; cluster 3 by mild stroke and mild OSA; and cluster 4 by moderate OSA and mild stroke. Compared to cluster 3 and after adjustment for baseline stroke severity, cluster 1 and cluster 2 had worse 90-day functional outcome and cluster 1 also had worse quality of life. No difference in cognitive outcome or stroke recurrence rate was noted by cluster. CONCLUSION: Post-stroke OSA is a heterogeneous disorder with different clinical phenotypes associated with stroke outcomes, including both daily function and quality of life. The unique presentations of OSA after stroke may have important implications for stroke prognosis and personalized treatment strategies.


Subject(s)
Ischemic Stroke , Sleep Apnea, Obstructive , Stroke , Humans , Ischemic Stroke/complications , Quality of Life , Stroke/epidemiology , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/epidemiology , Sleep Apnea, Obstructive/diagnosis , Phenotype , Cluster Analysis
5.
Phys Rev Lett ; 131(20): 201801, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-38039482

ABSTRACT

A new dark sector antibaryon, denoted ψ_{D}, could be produced in decays of B mesons. This Letter presents a search for B^{+}→ψ_{D}+p (and the charge conjugate) decays in e^{+}e^{-} annihilations at 10.58 GeV, using data collected in the BABAR experiment. Data corresponding to an integrated luminosity of 398 fb^{-1} are analyzed. No evidence for a signal is observed. Branching fraction upper limits in the range from 10^{-7}-10^{-5} are obtained at 90% confidence level for masses of 1.0

6.
Pathog Immun ; 8(1): 64-76, 2023.
Article in English | MEDLINE | ID: mdl-37830077

ABSTRACT

Background: Cutibacterium acnes is a common commensal of human skin but may also present as an opportunistic pathogen in prosthetic joint and wound infections. Unfortunately, few complete genomes of C. acnes are publicly available, and even fewer are of isolates associated with infection. Here we report the isolation, characterization, and complete genomes of 2 C. acnes isolates from a surgical site infection of an elbow. Methods: We used standard microbiological methods for phenotypic characterization and performed whole genome sequencing on 2 C. acnes isolates using a combination of short-read and long-read sequencing. Results: Antibiotic susceptibility testing showed beta-lactamase negative and low minimal inhibitory concentrations to all antibiotics tested, with the exception of metronidazole. We assembled complete genomes of the 2 isolates, which are approximately 2.5 megabases in length. The isolates belong to the single-locus sequence type (SLST) H1 and the multi-locus sequence type (MLST) IB. Both isolates have similar composition of known virulence genes, and we found no evidence of plasmids but did find phage-associated genes. Notably, the 2 genomes are 99.97% identical but contain a large genomic inversion encompassing approximately half of the genome. Conclusions: This is the first characterization of this large-scale genomic inversion in nearly identical isolates from the same wound. This report adds to the limited numbers of publicly available infection-associated complete genomes of C. acnes.

7.
Pediatrics ; 152(5)2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37823246

ABSTRACT

BACKGROUND: Pediatric patients with behavioral needs are frequently admitted to the hospital for medical care; when behavioral crises occur, patients and staff are at risk for injury. Our aim was to implement a behavior response team (BRT) to increase the days between employee injury due to aggressive patient interactions on the inpatient medical units from 99 to 150 over 1 year. METHODS: A multidisciplinary team used quality improvement methods to design and implement the BRT system that includes 2 options: huddle to proactively plan for patients exhibiting early signs of escalation and STAT for immediate help for patients with imminent risk of harm to self or others. Using run and statistical process control charts, we tracked events per month, days between Occupational Safety & Health Administration-recordable events, and violent restraint use over time for 1 year after implementation. Staff pre and postimplementation surveys were compared to assess staff perception of safety and support provided by the BRT intervention. RESULTS: The BRT was implemented across the inpatient system in July 2020, with an average number of 13 events per month. Days between Occupational Safety & Health Administration-recordable events remained stable with a maximum of 134 days. Restraint use remained stable at 0.74 per 1000 patient days. The perception of behavioral support available to staff increased significantly pre to postsurvey. CONCLUSIONS: The implementation of a BRT can improve staff perception of support and confidence in safely caring for patients with behavior needs on the inpatient medical unit, although additional provider- and system-level improvements are needed to prevent employee injuries.


Subject(s)
Aggression , Quality Improvement , Humans , Child , Behavior Therapy , Critical Care , Hospitals, Pediatric
8.
PEC Innov ; 3: 100214, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37743957

ABSTRACT

Objective: To explore patient and family perspectives of a discharge bedside board for supporting engagement in patient care and discharge planning to inform tool revision. Methods: This qualitative descriptive study included 45 semi-structured interviews with a purposeful sample of English-speaking patients (n = 44; mean age 58.5 years) and their family members (n = 5) across seven adult inpatient units at a tertiary acute care hospital in mid-western Canada. Thematic (interviews), content (board, organization procedure document), and framework-guided integrated (all data) analyses were performed. Results: Four themes were generated from interview data: understanding the board, included essential information to guide care, balancing information on the board, and maintaining a sense of connection. Despite application inconsistencies, documented standard procedures aligned with recommended board (re)orientation, timely patient-friendly content, attention to privacy, and patient-provider engagement strategies. Conclusion: Findings indicate the tool supported consultation and some involvement level engagement in patient care and discharge. Board information was usually valued, however, perceived procedural gaps in tool education, privacy, and the quality of tool-related communication offer opportunities to strengthen patients' and families' tool experience. Innovation: Novel application of a continuum engagement framework in the exploration of multiple data sources generated significant insights to guide tool revision.

9.
Front Rehabil Sci ; 4: 1176960, 2023.
Article in English | MEDLINE | ID: mdl-37546578

ABSTRACT

Introduction: Online community-based exercise (CBE) is a digital health intervention and rehabilitation strategy that promotes health among people living with HIV. Our aim was to describe the factors influencing initial implementation of a pilot online CBE intervention with adults living with HIV using a systems approach, as recommended by implementation science specialists. Methods: We piloted the implementation of a 6-month online CBE intervention and 6-month independent exercise follow up, in partnership with the YMCA in Toronto, Canada. We recruited adults living with HIV who identified themselves as safe to engage in exercise. The intervention phase included personalized exercise sessions online with a personal trainer; exercise equipment; access to online exercise classes; and a wireless physical activity monitor. Two researchers documented implementation factors articulated by participants and the implementation team during early implementation, defined as recruitment, screening, equipment distribution, technology orientation, and baseline assessments. Data sources included communication with participants; daily team communication; weekly team discussions; and in-person meetings. We documented implementation factors in meeting minutes, recruitment screening notes, and email communication; and analyzed the data using a qualitative descriptive approach using a systems engineering method called Cognitive Work Analysis. Results: Thirty-three adults living with HIV enrolled in the study (n = 33; median age: 52 years; cis-men: 22, cis-women: 10, non-binary: 1). Fifty-five factors influencing implementation, spanned five layers: (i) Natural, including weather and the COVID-19 virus; (ii) Societal, including COVID-19 impacts (e.g. public transit health risks impacting equipment pick-ups); (iii) Organizational, including information dissemination (e.g. tech support) and logistics (e.g. scheduling); (iv) Personal, including physical setting (e.g. space) and digital setting (e.g. device access); and (v) Human, including health (e.g. episodic illness) and disposition (e.g. motivation). The implementation team experienced heightened needs to respond rapidly; sustain engagement; and provide training and support. Additional organizational factors included a committed fitness training and research team with skills spanning administration and logistics, participant engagement, technology training, physical therapy, and research ethics. Conclusion: Fifty-five factors spanning multiple layers illustrate the complexities of online CBE with adults living with HIV. Initial implementation required a dedicated, rehabilitation-centred, multi-skilled, multi-stakeholder team to address a diverse set of factors.

10.
J Clin Aesthet Dermatol ; 16(6): 46-49, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37361367

ABSTRACT

Objective: Research exists examining sunburn risks, sun protective behaviors, and interventions among pool lifeguards; however, ocean lifeguard research is limited. This study aimed to determine sunburn prevalence and associations between sunburn with photoprotective attitudes and habits among Florida ocean lifeguards. Methods: A cross-sectional study was electronically administered in 2021 to ocean lifeguards using sun protection questions. Recruitment occurred through three lifeguard agencies. The frequency of self-reported sunburns from the prior season and the opinions and practices related to photoprotection and tanning were obtained. Results: Complete data were obtained from 77 (37%) of 207 lifeguards who served during the 2020 swimming season (mean [SD] age, 22.9 [8.31] years; 40 male (52.0%) and 37 female (48.0%)). Sunburn was common with only four (5.2%) lifeguards reporting no sunburn. In total, 26 (33.8%) reported five or more sunburns. The median sunburn frequency was three. Reporting three or more sunburns was positively associated with being a teenager (16 to 18 years) (aOR: 14.9, 95% CI 3.5 to 64.2) or young adult (19 to 23 years) (aOR: 6.4, 95% CI 1.6 to 25.2) and having a neutral opinion regarding sunscreen effectiveness (aOR: 4.5, 95% CI 1.1 to 18.7) in logistic regression models. Limitations: Self-reported sunburns were recalled and not clinically evaluated. Recall, participation, and social desirability biases may have been present. Conclusion: Ocean lifeguards reported appreciably high rates of sunburn, especially younger lifeguards. Increased photoprotection education, engineering controls, and research are warranted for this occupational group.

11.
Health Place ; 80: 102998, 2023 03.
Article in English | MEDLINE | ID: mdl-36921377

ABSTRACT

The inclusion of health-related indicators in composite measures of multiple deprivation introduces a risk of endogeneity bias when using the latter in health inequalities research. This bias may ultimately result in the inappropriate allocation of healthcare resources and maintenance of preventable health inequalities. Mitigation strategies to avoid this bias include removing the health-related indicators or using single constituent domains (such as income or employment class) in isolation. These strategies have not been widely validated. This study used population-level health and mortality data with a contemporary composite measure of multiple deprivation (Scottish Index of Multiple Deprivation; SIMD) to assess these mitigation strategies. The differences between deprivation methods (original, health excluded, and income domain) were negligible. The results of quantitative research on health inequalities are unlikely to be affected by endogeneity bias.


Subject(s)
Healthcare Disparities , Bias , Health Disparate Minority and Vulnerable Populations , Socioeconomic Factors , Humans , Scotland/epidemiology , Mortality , Health Status
13.
Ann R Coll Surg Engl ; 105(3): 196-202, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35617051

ABSTRACT

INTRODUCTION: Isolated volar dislocations of the distal radioulnar joint are reported as rare. We observed three such cases over a 12-month period. Literature to date consists of multiple case reports and case series with no structured reviews. There is debate as to incidence, mechanism, investigation, treatment and prognosis. METHODS: A case series and formal systematic review was performed. This included an analysis of the demographics, mechanism, presentation, investigation, treatment and outcome of the cases identified from the wider published series. FINDINGS: In total 99 cases of this injury were identified from 59 papers, with a further 9 cases having an associated ulna styloid fracture. CONCLUSIONS: This is a rare injury, representing up to 0.02% of all bony injuries, which is diagnosed late in 36% of cases. Inability to obtain a true lateral radiograph may contribute to the diagnosis being missed. Computed tomography scans are useful in suspected cases without radiographic confirmation. Acute cases are successfully treated with closed reduction in 78% of cases; however associated soft tissue injuries may need to be surgically addressed. Delayed presentation is more likely to require open surgery and preoperative MRI scans are indicated to aid surgical planning. Chronic instability rarely occurs and may need treatment with reconstruction or salvage. A good, subjective, result is reported in the majority of patients.


Subject(s)
Joint Dislocations , Radius Fractures , Ulna Fractures , Wrist Injuries , Humans , Wrist Injuries/diagnostic imaging , Wrist Injuries/surgery , Joint Dislocations/diagnostic imaging , Joint Dislocations/surgery , Wrist Joint/diagnostic imaging , Wrist Joint/surgery , Ulna Fractures/diagnostic imaging , Ulna Fractures/surgery , Radiography , Radius Fractures/diagnostic imaging , Radius Fractures/surgery
14.
AIDS Care ; 35(8): 1215-1223, 2023 08.
Article in English | MEDLINE | ID: mdl-33745403

ABSTRACT

Chronic pain is a common comorbidity in people with HIV (PWH), with prevalence estimates of 25-85%. Research in this area is growing, but significant gaps remain. A Global Task Force of HIV experts was organized to brainstorm a scientific agenda and identify measurement domains critical to advancing research in this field. Experts were identified through literature searches and snowball sampling. Two online questionnaires were developed by Task Force members. Questionnaire 1 asked participants to identify knowledge gaps in the field of HIV and chronic pain and identify measurement domains in studies of chronic pain in PWH. Responses were ranked in order of importance in Questionnaire 2, which was followed by a group discussion. 29 experts completed Questionnaire 1, 25 completed Questionnaire 2, and 21 participated in the group. Many important clinical and research priorities emerged, including the need to examine etiologies of chronic pain in PWH. Pain-related measurement domains were discussed, with a primary focus on domains that could be assessed in a standardized manner across various cohorts that include PWH in different countries. We collaboratively identified clinical and research priorities, as well as gaps in standardization of measurement domains, that can be used to move the field forward.


Subject(s)
Chronic Pain , HIV Infections , Humans , HIV Infections/complications , HIV Infections/epidemiology , Chronic Pain/epidemiology , Comorbidity
15.
Child Youth Care Forum ; 52(3): 509-531, 2023.
Article in English | MEDLINE | ID: mdl-35966643

ABSTRACT

Background: Technology and its use within mental health services has advanced dramatically over recent years. Opportunities for mental health services to utilise technology to introduce novel, effective, and more efficient means of delivering assessment, and treatment are increasing. Objective: The current rapid-evidence paper reviews evidence regarding the introduction of novel technology to support young people's mental health and psychological well-being. Methods: A rapid evidence review was conducted. PSYCHINFO and CINAHL were searched for research articles between 2016 and 2021 that were specific to young people, mental health, and technology developments within this domain. N = 27 studies which explored the introduction, feasibility, and value of technology for mental health purposes were included in a narrative synthesis. Quality or risk of bias analyses were not completed. Results: Overall, technological advancements in young people's care were considered positive and engaging for young people. Factors including resources, efficiency of care, engagement, therapeutic effectiveness, ethical considerations, therapeutic alliance, and flexibility were considered within this review. Nevertheless, potential barriers include clinician concerns, socioeconomic factors, and motivation. Conclusion: Effective and sustained use of technology within young people's mental health services will depend on the technology's usability, efficiency, and ability to engage young people. This paper expands on existing research by reviewing a broader range of technology proposed to support young people's mental health and well-being. This will assist in the application of novel technological advancements by indicating effectiveness, preferences, potential barriers, and recommendations for the feasibility and efficacy of introducing technology into young people's services.

16.
Cell Mol Life Sci ; 80(1): 15, 2022 Dec 23.
Article in English | MEDLINE | ID: mdl-36550225

ABSTRACT

Mononuclear phagocytes (MPs) play an active role in the immunological homeostasis of the urogenital tract. In the epididymis, a finely tuned balance between tolerance to antigenic sperm and immune activation is required to maintain epididymal function while protecting sperm against pathogens and stressors. We previously characterized a subset of resident MPs that express the CX3CR1 receptor, emphasizing their role in antigen sampling and processing during sperm maturation and storage in the murine epididymis. Bacteria-associated epididymitis is the most common cause of intrascrotal inflammation and frequently leads to reproductive complications. Here, we examined whether the lack of functional CX3CR1 in homozygous mice (CX3CR1EGFP/EGFP, KO) alters the ability of MPs to initiate immune responses during epididymitis induced by LPS intravasal-epididymal injection. Confocal microscopy revealed that CX3CR1-deficient MPs located in the initial segments of the epididymis displayed fewer luminal-reaching membrane projections and impaired antigen capture activity. Moreover, flow cytometry showed a reduction of epididymal KO MPs with a monocytic phenotype under physiological conditions. In contrast, flow cytometry revealed an increase in the abundance of MPs with a monocytic signature in the distal epididymal segments after an LPS challenge. This was accompanied by the accumulation of CD103+ cells in the interstitium, and the prevention or attenuation of epithelial damage in the KO epididymis during epididymitis. Additionally, CX3CR1 deletion induced downregulation of Gja1 (connexin 43) expression in KO MPs. Together, our study provides evidence that MPs are gatekeepers of the immunological blood-epididymis barrier and reveal the role of the CX3CR1 receptor in epididymal mucosal homeostasis by inducing MP luminal protrusions and by regulating the monocyte population in the epididymis at steady state as well as upon infection. We also uncover the interaction between MPs and CD103+ dendritic cells, presumably through connexin 43, that enhance immune responses during epididymitis. Our study may lead to new diagnostics and therapies for male infertility and epididymitis by identifying immune mechanisms in the epididymis.


Subject(s)
Epididymis , Epididymitis , Humans , Male , Mice , Animals , Epididymis/metabolism , Epididymitis/metabolism , Connexin 43/genetics , Connexin 43/metabolism , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism , Semen/metabolism , Spermatozoa/metabolism , CX3C Chemokine Receptor 1/genetics , CX3C Chemokine Receptor 1/metabolism
17.
J Am Stat Assoc ; 117(538): 547-560, 2022.
Article in English | MEDLINE | ID: mdl-36338275

ABSTRACT

Alzheimer's disease is a neurodegenerative condition that accelerates cognitive decline relative to normal aging. It is of critical scientific importance to gain a better understanding of early disease mechanisms in the brain to facilitate effective, targeted therapies. The volume of the hippocampus is often used in diagnosis and monitoring of the disease. Measuring this volume via neuroimaging is difficult since each hippocampus must either be manually identified or automatically delineated, a task referred to as segmentation. Automatic hippocampal segmentation often involves mapping a previously manually segmented image to a new brain image and propagating the labels to obtain an estimate of where each hippocampus is located in the new image. A more recent approach to this problem is to propagate labels from multiple manually segmented atlases and combine the results using a process known as label fusion. To date, most label fusion algorithms employ voting procedures with voting weights assigned directly or estimated via optimization. We propose using a fully Bayesian spatial regression model for label fusion that facilitates direct incorporation of covariate information while making accessible the entire posterior distribution. Our results suggest that incorporating tissue classification (e.g, gray matter) into the label fusion procedure can greatly improve segmentation when relatively homogeneous, healthy brains are used as atlases for diseased brains. The fully Bayesian approach also produces meaningful uncertainty measures about hippocampal volumes, information which can be leveraged to detect significant, scientifically meaningful differences between healthy and diseased populations, improving the potential for early detection and tracking of the disease.

18.
JCI Insight ; 7(19)2022 10 10.
Article in English | MEDLINE | ID: mdl-36214220

ABSTRACT

Intercellular communication is critical for homeostasis in mammalian systems, including the gastrointestinal (GI) tract. Exosomes are nanoscale lipid extracellular vesicles that mediate communication between many cell types. Notably, the roles of immune cell exosomes in regulating GI homeostasis and inflammation are largely uncharacterized. By generating mouse strains deficient in cell-specific exosome production, we demonstrate deletion of the small GTPase Rab27A in CD11c+ cells exacerbated murine colitis, which was reversible through administration of DC-derived exosomes. Profiling RNAs within colon exosomes revealed a distinct subset of miRNAs carried by colon- and DC-derived exosomes. Among antiinflammatory exosomal miRNAs, miR-146a was transferred from gut immune cells to myeloid and T cells through a Rab27-dependent mechanism, targeting Traf6, IRAK-1, and NLRP3 in macrophages. Further, we have identified a potentially novel mode of exosome-mediated DC and macrophage crosstalk that is capable of skewing gut macrophages toward an antiinflammatory phenotype. Assessing clinical samples, RAB27A, select miRNAs, and RNA-binding proteins that load exosomal miRNAs were dysregulated in ulcerative colitis patient samples, consistent with our preclinical mouse model findings. Together, our work reveals an exosome-mediated regulatory mechanism underlying gut inflammation and paves the way for potential use of miRNA-containing exosomes as a novel therapeutic for inflammatory bowel disease.


Subject(s)
CD11 Antigens , Colitis , Exosomes , Inflammation , Myeloid Cells , Animals , CD11 Antigens/genetics , CD11 Antigens/immunology , Colitis/genetics , Colitis/immunology , Exosomes/genetics , Exosomes/immunology , Inflammation/genetics , Inflammation/immunology , Inflammatory Bowel Diseases/immunology , Intestines/immunology , Lipids , Mammals/genetics , Mammals/immunology , Mice , MicroRNAs/immunology , Monomeric GTP-Binding Proteins/immunology , Myeloid Cells/immunology , NLR Family, Pyrin Domain-Containing 3 Protein/immunology , TNF Receptor-Associated Factor 6/immunology
19.
Opt Express ; 30(22): 40691-40703, 2022 Oct 24.
Article in English | MEDLINE | ID: mdl-36298999

ABSTRACT

The Brillouin instability (BI) due to stimulated Brillouin scattering (SBS) and the transverse (thermal) mode instability (TMI) due to stimulated thermal Rayleigh scattering (STRS) limit the achievable power in high-power lasers and amplifiers. The pump power threshold for BI increases as the core diameter increases, but the threshold for TMI may decrease as the core diameter increases. In this paper, we use a multi-time-scale approach to simultaneously model BI and TMI, which gives us the ability to find the fiber diameter with the highest power threshold. We formulate the equations to compare the thresholds of the combined and individual TMI and BI models. At the pump power threshold and below, there is a negligible difference between the full and individual models, as BI and TMI are not strong enough to interact with each other. The highest pump threshold occurs at the optimal core size of 43 µm for the simple double-clad geometry that we considered. We found that both effects contribute equally to the threshold, and the full BI and TMI model yields a similar threshold as the BI or TMI model alone. However, once the reflectivity is sufficiently large, we find in the full BI and TMI model that BI may trigger TMI and reduce the TMI threshold to a value lower than is predicted in simulations with TMI alone. This result cannot be predicted by models that consider BI and TMI separately. Our approach can be extended to more complex geometries and used for their optimization.

20.
Trop Anim Health Prod ; 54(5): 263, 2022 Aug 12.
Article in English | MEDLINE | ID: mdl-35960378

ABSTRACT

This study determined the effect of purified condensed tannin inclusion levels in a diet on production, haematological indices, blood biochemical components, meat quality and methane emission by yearling indigenous male Bapedi sheep on a grass hay and sheep pellet-based diet in a 28-day trial. The diets contained similar (P > 0.05) nutrients but with different (P < 0.05) purified condensed tannin supplementation levels. A complete randomized design was used. Twenty-four yearling male Bapedi sheep were assigned to four dietary treatments having different purified condensed tannin levels of 0 (GH80P20PCT0), 30 (GH80P20PCT30), 40 (GH80P20PCT40) and 50 (GH80P20PCT50) g/kg DM. A quadratic type of equation was also used to determine condensed tannin supplementation levels for optimal performance and methane emission reduction by sheep. Supplementing diets with purified condensed tannins did not affect (P > 0.05) diet intake, digestibility and live weight gain of male Bapedi sheep. Supplementing diets with purified condensed tannins did not affect (P > 0.05) blood components of male Bapedi sheep. Inclusion of condensed tannins in the diets did not affect (P > 0.05) Bapedi sheep meat pH and sensory attributes. However, supplementing diets with purified condensed tannins decreased (P < 0.05) methane emission by 51 to 60%. A 49.08 g supplementation level with purified condensed tannins per kg DM diet was calculated, with the use of quadratic equations, to result in the lowest methane emission by male Bapedi sheep. The meat of male Bapedi rams on diets containing 30, 40 or 50 g of purified condensed tannins per kg DM contained higher (P < 0.05) antioxidant activities than those from rams fed a diet without purified condensed tannins. These results indicate that purified condensed tannin supplementation levels of 0, 30, 40 or 50 g/kg DM diet had no adverse effects on growth performance, blood profiles and meat sensory attributes of male Bapedi sheep. However, supplementation levels of 30, 40 or 50 g of purified condensed tannins per kg DM diet reduced methane emission by 51 to 60%, and increased sheep meat antioxidant activity values. Supplementing diets with purified condensed tannins has the potential to reduce methane production and emission by sheep. However, long-term studies are recommended to ascertain the present findings.


Subject(s)
Methane , Proanthocyanidins , Animal Feed/analysis , Animals , Diet/veterinary , Digestion , Male , Meat , Rumen , Sheep , Tannins
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