Age-associated Senescent - T Cell Signaling Promotes Type 3 Immunity that Inhibits the Biomaterial Regenerative Response.

Aging is associated with immunological changes that compromise response to infections and vaccines, exacerbate inflammatory diseases and can potentially mitigate tissue repair. Even so, age-related changes to the immune response to tissue damage and regenerative medicine therapies remain unknown. Here, it is characterized how aging induces changes in immunological signatures that inhibit tissue repair and therapeutic response to a clinical regenerative biological scaffold derived from extracellular matrix. Signatures of inflammation and interleukin (IL)-17 signaling increased with injury and treatment both locally and regionally in aged animals, and computational analysis uncovered age-associated senescent-T cell communication that promotes type 3 immunity in T cells. Local inhibition of type 3 immune activation using IL17-neutralizing antibodies improves healing and restores therapeutic response to the regenerative biomaterial, promoting muscle repair in older animals. These results provide insights into tissue immune dysregulation that occurs with aging that can be targeted to rejuvenate repair.

Novel Serum Biomarkers Associated With Pediatric Hepatic Encephalopathy: A Systematic Review.

BACKGROUND: The pathophysiology of pediatric hepatic encephalopathy (HE) is not well understood. Various serum biomarkers associated with HE may provide insight into its pathology, but their use and interpretation in clinical practice for diagnosis and prognostication remain undetermined. We sought to investigate reported correlations of serum biomarkers with presence and degree of HE in children. METHODS: We conducted a systematic review of studies examining novel serum biomarkers and cytokines in association with HE that included children on PubMed, Embase, Lilacs, and Scopus. We utilized Covidence for abstract and text review by 2 independent reviewers for each study. RESULTS: We reviewed 2824 unique publications; 15 met criteria for inclusion. Categories of biomarkers reported were inflammatory cytokines, products of amino acid metabolism, trace elements and vitamins, and hepatic and neuro biomarkers. Of 19 individual biomarkers, only 5 were measured in more than 1 study. Elevations in interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were most commonly reported as associated with HE. Notably, we observed lower average IL-6 and TNF-alpha levels in pediatric-only studies compared to mixed age studies. Overall, high bias and poor applicability to our review question was observed. We encountered low numbers of studies with pediatric focus, and few conducted with low bias study designs. CONCLUSION: Investigated biomarkers span a large range of categories and suggest potentially useful correlations with HE. Further well-designed prospective biomarker research is necessary to better elucidate the pathogenesis of HE in children and improve early detection and clinical care.

Transfer learning in a biomaterial fibrosis model identifies in vivo senescence heterogeneity and contributions to vascularization and matrix production across species and diverse pathologies.

Cellular senescence is a state of permanent growth arrest that plays an important role in wound healing, tissue fibrosis, and tumor suppression. Despite senescent cells' (SnCs) pathological role and therapeutic interest, their phenotype in vivo remains poorly defined. Here, we developed an in vivo-derived senescence signature (SenSig) using a foreign body response-driven fibrosis model in a p16-CreERT2;Ai14 reporter mouse. We identified pericytes and "cartilage-like" fibroblasts as senescent and defined cell type-specific senescence-associated secretory phenotypes (SASPs). Transfer learning and senescence scoring identified these two SnC populations along with endothelial and epithelial SnCs in new and publicly available murine and human data single-cell RNA sequencing (scRNAseq) datasets from diverse pathologies. Signaling analysis uncovered crosstalk between SnCs and myeloid cells via an IL34-CSF1R-TGFßR signaling axis, contributing to tissue balance of vascularization and matrix production. Overall, our study provides a senescence signature and a computational approach that may be broadly applied to identify SnC transcriptional profiles and SASP factors in wound healing, aging, and other pathologies.

Helminth egg derivatives as proregenerative immunotherapies.

The immune system is increasingly recognized as an important regulator of tissue repair. We developed a regenerative immunotherapy from the helminth Schistosoma mansoni soluble egg antigen (SEA) to stimulate production of interleukin (IL)-4 and other type 2-associated cytokines without negative infection-related sequelae. The regenerative SEA (rSEA) applied to a murine muscle injury induced accumulation of IL-4-expressing T helper cells, eosinophils, and regulatory T cells and decreased expression of IL-17A in gamma delta (γδ) T cells, resulting in improved repair and decreased fibrosis. Encapsulation and controlled release of rSEA in a hydrogel further enhanced type 2 immunity and larger volumes of tissue repair. The broad regenerative capacity of rSEA was validated in articular joint and corneal injury models. These results introduce a regenerative immunotherapy approach using natural helminth derivatives.

It's a Hard Knock Life: How Kids With Mild Traumatic Brain Injuries Are Treated.

OBJECTIVES: The diagnosis and treatment of mild traumatic brain injuries (mTBIs) by emergency medicine providers is greatly varied. Because of the frequency and long-term consequences associated with pediatric head injuries, it is crucial that adequate counseling is provided in acute care settings. The purpose of our study is to evaluate existing practices at Loyola University Medical Center emergency department to address inconsistencies in diagnostic or discharge practices and determine future quality improvement measures. METHODS: A retrospective cohort study was conducted at an academic hospital emergency department of patient records from 2017 to 2020. Demographic, diagnostic, and discharge data were summarized, and Pearson χ2 tests and Fisher exact tests were performed to determine associations among patient characteristics and provider practices. RESULTS: A total of 1160 patients met inclusion criteria for analysis. In terms of diagnostic procedure, 31.6% of providers did not uniformly use existing screening criteria, such as PECARN, to determine if CT scans were needed for mTBI evaluation. Most discharge instructions were based on a generalized template on epic (91.9%). Only a minority of providers prepared patient-specific instructions through written, verbal, or other supplemental materials. The most common formats included epic only (46.1%), epic and personalized written instructions (20.2%), and epic and verbal instructions (12.4%). Follow-up care instructions were provided to 93% of patients who received discharged instructions, mainly for primary care (96.7%), sports medicine (1.58%), neurology (0.65%), or other providers (1.11%). CONCLUSIONS: There is a lack of consistency in the evaluation and education of mTBI in pediatric patients. There is a need for personalized discharge instructions to ensure adequate patient and parent understanding and compliance. Further studies looking at long-term outcomes in these patients would also be beneficial.

Beyond the bundle: Clinical controversies in the management of sepsis in emergency medicine patients.

Sepsis is a condition characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection. The emergency department (ED) serves as a crucial entry point for patients presenting with sepsis. Given the heterogeneous presentation and high mortality rate associated with sepsis and septic shock, several clinical controversies have emerged in the management of sepsis. These include the use of novel therapeutic agents like angiotensin II, hydrocortisone, ascorbic acid, thiamine ("HAT") therapy, and levosimendan, Additionally, controversies with current treatments in vasopressor dosing, and the use of and balanced or unbalanced crystalloid are crucial to consider. The purpose of this review is to discuss clinical controversies in the management of septic patients, including the use of novel medications and dosing strategies, to assist providers in appropriately determining what treatment strategy is best suited for patients.

Beyond Broadway: Analysis of Qualitative Characteristics of and Individual Responses to Creatively Able, a Music and Movement Intervention for Children with Autism.

Movement in response to music represents one of the natural social environments in which physical activity occurs. The study of music and movement, including dance, requires a careful, holistic consideration of many features, which may include music, physical activity, motor learning, social engagement, emotion, and creativity. The overarching goal of this manuscript is to examine qualitative characteristics of and individual responses to a music and movement intervention (Creatively Able) for children with Autism Spectrum Disorder (ASD). We provide a description of Creatively Able, illustrating how the program design and physical and social environment were informed by children's needs and preferences in order to provide an enriched environment in which to promote multiple systems in children with ASD. Using data from two pilot studies with 20 children with ASD, we illustrate how researchers can use observational research methods to measure important aspects of the social environment (e.g., children's engagement during intervention sessions) as well as engagement of potential underlying behavioral mechanisms (e.g., self-regulation) that might reduce clinical symptoms. We further illustrate how individual responses to intervention (e.g., improvements in behaviors or symptoms) can be studied in physically active interventions. Our pilot study results showed group-level reductions in Stereotyped and Compulsive behaviors of 8% and 4%, respectively; posthoc analysis revealed that there were substantial individual differences in children's responses to the intervention. This research illustrates robust methods that can be applied to intervention research to improve our understanding of important features of interventions that might help promote development in various domains, including executive functions and self-regulation.

Correlation of cervical cytology with high-risk HPV molecular diagnosis, genotypes, and histopathology--A four year study from the UAE.

BACKGROUND: Cervical cancer is one of the most common cancers among women in the world and in the Middle East. Its prevention and screening strategies assume great importance especially in view of the ability to identify the illness at an early stage and disrupt its progression toward neoplasia. Cervical cancer screening program of our center in UAE as well as this study is oriented in this direction. METHODS: Cervical cytology data encompassing 4 years (2011-2014) was compiled and analyzed for 14,950 cases to assess the abnormal smear reporting pattern, correlation with biopsy histopathology, HPV high-risk screening data, and HPV genotype prevalence among patients with abnormal smear test, as well as in relation to the respective nationalities of patients. RESULTS: Abnormal smear rates as well as HPV high-risk positivity correlated well with established data. Cytology-histology correlation was good. HPV high-risk type 16 was the commonest, type 18 which is the second common type worldwide was less frequently detected, several other high risk subtypes such as 51, 31 as well as rare types such as 66, 56, and 59 were detected in a significant number of patients. CONCLUSION: Assessment of cervical cytology reporting pattern, correlation of cervical cytology with HPV molecular diagnosis, and biopsy histopathology is a useful way to audit our work and a good quality control practice. Higher prevalence of HPV HR types such as type 51, 31 as well as 66, 56, and 59 found in the present as well as many similar other studies apart from the commonest subtype 16 may imply necessity for development of more targeted and multivalent anti-HPV vaccines for protection of women in our region. HPV genotypes correlation with the nationalities of patients is useful from an epidemiological standpoint to plan preventive strategies.