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Project INTERprofessional Autism Collaborative Training (INTERACT) is an interprofessional education program designed to prepare graduate students in psychology, special education, and speech-language pathology to work with autistic children with moderate to severe intellectual disabilities. The rising prevalence of autism, coupled with increased appreciation for interprofessional approaches to service delivery, indicates the need for university training programs to prepare graduate students to work interprofessionally with this population; yet descriptions of such programs and their effectiveness are not reported in the literature. In this article, we explain the process through which an interprofessional faculty team developed Project INTERACT, describe the sequence of coursework and team-based clinical experiences that comprise the program, and present preliminary data regarding its effectiveness. Twenty-four graduate students in psychology, special education, and speech-language pathology participated in this quantitative study. We report results from three rating scales that participants completed at program entry, midpoint, and program exit. Participants endorsed positive attitudes toward interprofessional practice and demonstrated high levels of knowledge about autism. Self-rated knowledge and abilities in interprofessional practice increased significantly by program exit. Project INTERACT scholars developed knowledge and skills related to understanding, assessing, and treating autistic children with intellectual disabilities, through the lens of team-based interprofessional collaboration. We discuss implications for practice with Project INTERACT.

Pediatric - type low - grade glioma (pLGG) is the most common central nervous system tumor in children, and most pLGG exhibits non -invasive clinical behavior with a good prognosis. Total surgical resection is an important prognostic factor, and patients can achieve long-term survival after total tumor resection. However, tumors in deep location such as brain stem and optic pathway cannot be completely removed by surgery. Chemotherapy is the first choice of adjuvant treatment when the clinical symptoms of pLGG worsen or imaging progress. In recent years, in addition to traditional chemotherapy, the development and application of targeted therapy drugs have also made great progress. This article reviews the research progress and challenges of chemotherapy and targeted therapy of pLGG, in order to provide guidance for clinical practice.

Abstract The incidence and prevalence of dialysis in Taiwan are high compared to other regions. Consequently, mitigating chronic kidney disease (CKD) and the worsening of kidney function have emerged as critical healthcare priorities in Taiwan. Heat stress is known to be a significant risk factor for CKD and kidney function impairment. However, differences in the impact of heat stress between males and females remains unexplored. We conducted this retrospective cross-sectional analysis using data from the Taiwan Biobank (TWB), incorporating records of the wet bulb globe temperature (WBGT) during midday (11 AM–2 PM) and working hours (8 AM–5 PM) periods based on the participants’ residential address. Average 1-, 3-, and 5-year WBGT values prior to the survey year were calculated and analyzed using a geospatial artificial intelligence-based ensemble mixed spatial model, covering the period from 2010 to 2020. A total of 114,483 participants from the TWB were included in this study, of whom 35.9% were male and 1053 had impaired kidney function (defined as estimated glomerular filtration rate

Abstract Respiratory infection by Pseudomonas aeruginosa, common in hospitalized immunocompromised and immunocompetent ventilated patients, can be life-threatening because of antibiotic resistance. This raises the question of whether the host’s immune system can be educated to combat this bacterium. Here we show that prior exposure to a single low dose of lipopolysaccharide (LPS) protects mice from a lethal infection by P. aeruginosa. LPS exposure trained the innate immune system by promoting expansion of neutrophil and interstitial macrophage populations distinguishable from other immune cells with enrichment of gene sets for phagocytosis- and cell-killing-associated genes. The cell-killing gene set in the neutrophil population uniquely expressed Lgals3, which encodes the multifunctional antibacterial protein, galectin-3. Intravital imaging for bacterial phagocytosis, assessment of bacterial killing and neutrophil-associated galectin-3 protein levels together with use of galectin-3-deficient mice collectively highlight neutrophils and galectin-3 as central players in LPS-mediated protection. Patients with acute respiratory failure revealed significantly higher galectin-3 levels in endotracheal aspirates (ETAs) of survivors compared to non-survivors, galectin-3 levels strongly correlating with a neutrophil signature in the ETAs and a prognostically favorable hypoinflammatory plasma biomarker subphenotype. Taken together, our study provides impetus for harnessing the potential of galectin-3-expressing neutrophils to protect from lethal infections and respiratory failure.

Abstract Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available. We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning. Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex. Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.

To overcome the limited application forms and inadequate therapeutic effects of 3D-printed scaffolds and osteogenic drug carriers. Nonetheless, concerns persist regarding the negative effects of burst and nonsustained release. In this study, we further enhanced the osteoinductive potential of 3D-printed BAG scaffolds by coating them with simvastatin (SIM) and poly(lactic-co-glycolic acid) (PLGA) with sustained release properties. Morphological assessment through SEM revealed evenly coated 3D-printed BAG scaffolds (BAG/PLGA/SIM), which showed sustained SIM release properties in vitro. The SIM released from BAG/PLGA/SIM still exhibited osteogenic activity in the augmentation of ALP activity and mineralization in mesenchymal stem cells. In an animal study of rat calvarial bone defects, both SIM-loaded BAG scaffolds, BAG/PLGA/SIM and BAG/PLGA/5 × SIM, significantly improved bone regeneration. Moreover, the IHC analysis of BMP2 and vWF expression also exhibited significant increases in both SIM-loaded BAG scaffolds. Notably, a higher SIM concentration (BAG/PLGA/5 × SIM) did not outperform a lower SIM concentration (BAG/PLGA/SIM) in promoting new bone formation. In conclusion, BAG/PLGA/SIM scaffolds could provide an excellent 3D architecture with sustained SIM release properties in vitro and excellent osteogenic properties for bone repair in vivo. The drug-loading method on 3D-printed BAG scaffolds could provide an alternative strategy for the development of multifunctional scaffolds for clinical applications.

ABSTRACTHuman metapneumovirus (HMPV) is a primary cause of acute respiratory infection, yet there are no approved vaccines or antiviral therapies for HMPV. Early host responses to HMPV are poorly characterized, and further understanding could identify important antiviral pathways. Type III interferon (IFN-λ) displays potent antiviral activity against respiratory viruses and is being investigated for therapeutic use. However, its role in HMPV infection remains largely unknown. Here, we show that IFN-λ is highly upregulated during HMPV infection in vitro in human and mouse airway epithelial cells and in vivo in mice. We found through several immunological and molecular assays that type II alveolar cells are the primary producers of IFN-λ. Using mouse models, we show that IFN-λ limits lung HMPV replication and restricts virus spread from upper to lower airways but does not contribute to clinical disease. Moreover, we show that IFN-λ signaling is predominantly mediated by CD45- non-immune cells. Mice lacking IFN-λ signaling showed diminished loss of ciliated epithelial cells and decreased recruitment of lung macrophages in early HMPV infection along with higher inflammatory cytokine and interferon-stimulated gene expression, suggesting that IFN-λ may maintain immunomodulatory responses. Administration of IFN-λ for prophylaxis or post-infection treatment in mice reduced viral load without inflammation-driven weight loss or clinical disease. These data offer clinical promise for IFN-λ in HMPV treatment.IMPORTANCEHuman metapneumovirus (HMPV) is a common respiratory pathogen and often contributes to severe disease, particularly in children, immunocompromised people, and the elderly. There are currently no licensed HMPV antiviral treatments or vaccines. Here, we report novel roles of host factor IFN-λ in HMPV disease that highlight therapeutic potential. We show that IFN-λ promotes lung antiviral responses by restricting lung HMPV replication and spread from upper to lower airways but does so without inducing lung immunopathology. Our data uncover recruitment of lung macrophages, regulation of ciliated epithelial cells, and modulation of inflammatory cytokines and interferon-stimulated genes as likely contributors. Moreover, we found these roles to be distinct and non-redundant, as they are not observed with knockout of, or treatment with, type I IFN. These data elucidate unique antiviral functions of IFN-λ and suggest IFN-λ augmentation as a promising therapeutic for treating HMPV disease and promoting effective vaccine responses.

Abstract Kt/V and URR (urea reduction ratio) measurements represent dialysis adequacy. Single-pool Kt/V is theoretically a superior method and is recommended by the Kidney Disease Outcomes Quality Initiative guidelines. However, the prognostic value of URR compared with Kt/V for all-cause mortality is unknown. The effect modifiers and cut-off values of the two parameters have not been compared. We investigated 2615 incident hemodialysis patients with URR of 72% and Kt/V (Daugirdas) of 1.6. The average patient age was 59 years, 50.7% were female, and 1113 (40.2%) died within 10 years. URR and Kt/V were both positively associated with nutrition factors and female sex and negatively associated with body weight and heart failure. In Cox regression mod-els for all-cause mortality, the hazard ratios (HRs) of high URR groups (65–70%, 70–75%, and > 75%) and the URR 1.7) and the Kt/V 70% and Kt/V > 1.4 were associated with a higher survival rate. Kt/V may have weaker prognostic value for women.

Background and aims Gender differences in the written language of autistic individuals are an overlooked but important area of research. We contend that the gender differences in spoken language of autistic individuals may extend to written language, mirroring the gender differences of writing in the general population and reflecting the shared dimensionality of oral and written language. Our research question was: Do autistic adolescent females demonstrate written language characteristics, across persuasive, expository, and narrative genres, that are distinct from those of autistic adolescent males and non-autistic (NA) adolescent females? Methods We performed a secondary, exploratory analysis on writing samples collected from 18 participants (11 autistic males, three autistic females, and four NA females) from a larger investigation of autistic adolescents’ writing skills. Each participant completed three writing samples—one persuasive, one expository, and one narrative (for a total of 54 writing samples). We compared sample length (total number of words), writing productivity (words written per minute), syntactic length (mean length of T-unit in words), vocabulary diversity (type-token ratio), and macrostructure of autistic females’ samples to autistic males’ and NA females’ samples. Results Based on non-parametric analyses using variable medians, autistic males, but not autistic females, wrote significantly shorter expository samples than NA females. Autistic males’ writing productivity was significantly lower in the persuasive and expository genres than both autistic females and NA females. Several other comparisons of sample length, productivity, vocabulary diversity, and persuasive and narrative macrostructure yielded large effect sizes but were not statistically significant. Conclusions Though our small sample sizes prevent us from drawing generalizable conclusions, we observed that some gender-specific findings of the current study differ from previous findings based on a single autistic group (females and males combined). Combining data of autistic females with autistic males may cloud the distinct written language characteristics of each group. Implications Our findings, especially when situated in the context of relevant literature, suggest that larger-scale investigation of gender differences in written language is essential in order to more fully describe the unique characteristics of autistic females. Clinicians should be prepared to support autistic writers’ needs for producing written language to meet their developmental, academic, social, and employment-related goals.

Necrotizing enterocolitis (NEC) is a gastrointestinal complication of premature infants with high rates of morbidity and mortality. A comprehensive view of the cellular changes and aberrant interactions that underlie NEC is lacking. This study aimed at filling in this gap. We combine single-cell RNA sequencing (scRNAseq), T-cell receptor beta (TCRβ) analysis, bulk transcriptomics, and imaging to characterize cell identities, interactions, and zonal changes in NEC. We find an abundance of proinflammatory macrophages, fibroblasts, endothelial cells as well as T cells that exhibit increased TCRβ clonal expansion. Villus tip epithelial cells are reduced in NEC and the remaining epithelial cells up-regulate proinflammatory genes. We establish a detailed map of aberrant epithelial-mesenchymal-immune interactions that are associated with inflammation in NEC mucosa. Our analyses highlight the cellular dysregulations of NEC-associated intestinal tissue and identify potential targets for biomarker discovery and therapeutics.

Non-insulin-based insulin resistance (IR) indices serve as the indicators of metabolic syndrome (MetS) but have limited value for predicting clinical outcomes. Whether the obesity paradox affects the predictive value of these indicators in patients with chronic kidney disease (CKD) remains unknown. We investigated whether MetS and non-insulin-based IR indices can predict all-cause mortality and renal outcomes in a prospective observational study with stage 1–4 CKD Asians (N = 2,457). These IR indices were associated with MetS. A Cox regression model including body mass index (BMI) revealed an association between MetS and renal outcomes. Among the IR indices, only high triglyceride–glucose (TyG) index was associated with adverse renal outcomes: the hazard ratio of Q4 quartile of the TyG index was 1.38 (1.12–1.70). All-cause mortality was marginally associated with MetS but not high IR indices. Low TyG and TyG–BMI indices as well as low BMI and triglyceride were paradoxically associated with increased risks of clinical outcomes. The triglyceride-to-high-density lipoprotein cholesterol ratio and metabolic score for IR indices were not associated with clinical outcomes. In conclusion, MetS and TyG index predict renal outcome and obesity paradox affects the prediction of IR indices in patients with stage 1–4 CKD.

IntroductionKlebsiella pneumoniae (Kp) is a common cause of hospital-acquired pneumonia. Although previous studies have suggested that evasion of phagocytic uptake is a virulence determinant of Kp, few studies have examined phagocytosis sensitivity in clinical Kp isolates.MethodsWe screened 19 clinical respiratory Kp isolates that were previously assessed for mucoviscosity for their sensitivity to macrophage phagocytic uptake, and evaluated phagocytosis as a functional correlate of in vivo Kp pathogenicity.ResultsThe respiratory Kp isolates displayed heterogeneity in the susceptibility to macrophage phagocytic uptake, with 14 out of 19 Kp isolates displaying relative phagocytosis-sensitivity compared to the reference Kp strain ATCC 43816, and 5 out of 19 Kp isolates displaying relative phagocytosis-resistance. Intratracheal infection with the non-mucoviscous phagocytosis-sensitive isolate S17 resulted in a significantly lower bacterial burden compared to infection with the mucoviscous phagocytosis-resistant isolate W42. In addition, infection with S17 was associated with a reduced inflammatory response, including reduced bronchoalveolar lavage fluid (BAL) polymorphonuclear (PMN) cell count, and reduced BAL TNF, IL-1β, and IL-12p40 levels. Importantly, host control of infection with the phagocytosis-sensitive S17 isolate was impaired in alveolar macrophage (AM)-depleted mice, whereas AM-depletion had no significant impact on host defense against infection with the phagocytosis-resistant W42 isolate.ConclusionAltogether, these findings show that phagocytosis is a primary determinant of pulmonary clearance of clinical Kp isolates.