Interleukin 8-CXCR2-mediated neutrophil extracellular trap formation in biliary atresia associated with neutrophil extracellular trap-induced stellate cell activation.

Background And Aims: Biliary atresia (BA) entails an inflammatory sclerosing lesion of the biliary tree, with prominent fibrosis in infancy. Previous studies revealed that neutrophil-activating IL-8 and neutrophil extracellular traps (NETs) positively correlated with bilirubin and the risk of liver transplant. The aims of this study were to determine the mechanism of NET formation (NETosis) in BA and whether NETs induce stellate cell activation.

Outcomes for Degenerative Cervical Myelopathy Following Implementation of the AO Spine International Guidelines: A Single-Centre Service Evaluation.

Introduction: Degenerative cervical myelopathy (DCM) is a syndrome of symptomatic cervical spinal cord compression due to degenerative spinal changes. Until recently there was no formal consensus on exactly which patients are suitable for surgical or conservative management. The AO Spine international guidelines were introduced to address this issue, based on the best available current evidence.

Mechanisms of memory-supporting neuronal dynamics in hippocampal area CA3.

Hippocampal CA3 is central to memory formation and retrieval. Although various network mechanisms have been proposed, direct evidence is lacking. Using intracellular V recordings and optogenetic manipulations in behaving mice, we found that CA3 place-field activity is produced by a symmetric form of behavioral timescale synaptic plasticity (BTSP) at recurrent synapses among CA3 pyramidal neurons but not at synapses from the dentate gyrus (DG).

Self-management interventions for chronic widespread pain including fibromyalgia: a systematic review and qualitative evidence synthesis.

Supporting behavioural self-management is increasingly important in the care for chronic widespread pain (CWP), including fibromyalgia. Understanding peoples' experiences of these interventions may elucidate processes and mechanisms that lead to or hinder their intended impact. We conducted a systematic review and thematic synthesis of qualitative studies exploring peoples' experiences of self-management interventions for CWP, including fibromyalgia.

Inclusive Excellence: A Roadmap to Cultivating Belonging for Faculty of Color in Physical Therapy Education.

Cultivating a sense of belonging among faculty of color decreases feelings of isolation and marginalization, translating to increased job satisfaction and retention. This roadmap for cultivating a sense of belonging for faculty of color highlights the following critical strategies: (1) adopting inclusive leadership practices, (2) understanding professional and personal identities, (3) mitigating cultural taxation, (4) minimizing microaggressions and racism, (5) providing mentorship, and (6) prioritizing acculturation over assimilation. By following this roadmap, physical therapy programs can work toward cultivating a greater sense of belonging for faculty of color, enabling them to thrive in their roles and feel valued and respected as integral members of the academic community.

Meeting the Health Needs of Society Through Curricular Innovation in Physical Therapist Education: Examples From 3 Entry-Level Programs.

Background And Purpose: Entry-level physical therapist (PT) education programs play a critical role in inspiring future leaders to become moral change agents, capable of understanding and addressing evolving societal health needs. Social reconstructionism represents an educational philosophy focused on alleviating pervasive inequities and improving the health of society; however, its application in PT education is not well understood. The purpose of this article is to describe the approach 3 entry-level PT programs used to manifest social reconstructionism within their curricula to foster social consciousness and strengthen moral agency.

Kmt2c restricts G-CSF-driven HSC mobilization and granulocyte production in a methyltransferase-independent manner.

Granulocyte colony-stimulating factor (G-CSF) is widely used to enhance myeloid recovery after chemotherapy and to mobilize hematopoietic stem cells (HSCs) for transplantation. Unfortunately, through the course of chemotherapy, cancer patients can acquire leukemogenic mutations that cause therapy-related myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). This raises the question of whether therapeutic G-CSF might potentiate therapy-related MDS/AML by disproportionately stimulating mutant HSCs and other myeloid progenitors.

Improving Pediatric Hypertension Screening in an Academic Primary Care Setting.

Introduction: Adherence to the American Academy of Pediatrics clinical practice guidelines for screening and managing high blood pressure (BP) is low. This team sought to improve recognition and documentation of relevant diagnoses in patients aged 13-20 years who presented to general pediatric clinics.

Methods: The primary outcome measure was the proportion of office visits for patients ages 13-20 with a BP ≥ 120/80 with a visit or problem list diagnosis of hypertension or elevated BP.

A mixed-method analysis of the contribution of informal sport to public health in Australia.

Informal sport is a growth area of sport participation but there has been limited examination of how informal and unstructured forms of participation may contribute to health outcomes that are important for public health. This article aims to address the current lack of data examining the health outcomes associated with informal sport participation and consider the potential role of informal sport within efforts to promote healthier communities through sport. The article seeks to broaden understanding of how informal sport participation can contribute to health outcomes, particularly with regard to increasing physical activity and enhancing mental health and social connection.

Disruption of polyunsaturated fatty acid biosynthesis drives STING-dependent acute myeloid leukemia cell maturation and death.

The role of polyunsaturated fatty acid (PUFA) biosynthesis in acute myeloid leukemia (AML) remains largely undefined. A comparative expression analysis of 35 genes encoding fatty acid biosynthesis enzymes showed that fatty acid desaturase 1 (FADS1) was highly expressed across multiple AML subtypes relative to healthy controls and that elevated FADS1 expression correlates with worse overall AML patient survival. Functionally, shRNA-mediated inhibition of FADS1 reduced AML cell growth in vitro and significantly delayed leukemia onset in an AML mouse model.

Are many sex/gender differences really power differences?

This research addresses the long-standing debate about the determinants of sex/gender differences. Evolutionary theorists trace many sex/gender differences back to natural selection and sex-specific adaptations. Sociocultural and biosocial theorists, in contrast, emphasize how societal roles and social power contribute to sex/gender differences beyond any biological distinctions.

Protein biomarkers GDF15 and FGF21 to differentiate mitochondrial hepatopathies from other pediatric liver diseases.

Background: Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) differentiate mitochondrial myopathies from other myopathies.

Changes over time in self-efficacy and the allocation of responsibility for health management tasks in pediatric liver transplant recipients: Targets to improve the transition process.

Background: The process of transition to adult-based care encompasses a critical period in the life of an adolescent and young adult living with a chronic illness and one that comes with an increase in the risk of poor health outcomes. As yet, there is a dearth of empirical data to help optimize this process to ensure the best long-term outcome.

Methods: This study used a principal components analysis to determine specific constructs measured by a revised version of the transition readiness survey used in our clinic.

Neonatal cholestasis in children with Alpha-1-AT deficiency is a risk for earlier severe liver disease with male predominance.

Background: Our objective was to better understand the natural history and disease modifiers of Alpha-1-antitrypsin deficiency (AATD), a common genetic liver disease causing hepatitis and cirrhosis in adults and children. The clinical course is highly variable. Some infants present with neonatal cholestasis, which can resolve spontaneously or progress to cirrhosis; others are well in infancy, only to develop portal hypertension later in childhood.

Chemical data evaluation: general considerations and approaches for IUPAC projects and the chemistry community (IUPAC Technical Report).

The International Union of Pure and Applied Chemistry (IUPAC) has a long tradition of supporting the compilation of chemical data and their evaluation through direct projects, nomenclature and terminology work, and partnerships with international scientific bodies, government agencies and other organizations. The IUPAC Interdivisional Subcommittee on Critical Evaluation of Data (ISCED) has been established to provide guidance on issues related to the evaluation of chemical data. In this first report we define the general principles of the evaluation of scientific data and describe best practices and approaches to data evaluation in chemistry.

A single centre service evaluation of degenerative cervical and thoracic myelopathy.

Background: Degenerative cervical myelopathy (DCM) and degenerative thoracic myelopathy (DTM) present with leg, bladder and bowel symptoms. If imaging confirms spinal cord compression both conditions are usually managed surgically. Surgical timing is important in patient management as it affects post-operative recovery and long-term outcomes.

A Comprehensive Mixed-Method Approach to Characterize the Source of Diurnal Tacrolimus Exposure Variability in Children: Systematic Review, Meta-analysis, and Application to an Existing Data Set.

Tacrolimus is widely reported to display diurnal variation in pharmacokinetic parameters with twice-daily dosing. However, the contribution of chronopharmacokinetics versus food intake is unclear, with even less evidence in the pediatric population. The objectives of this study were to summarize the existing literature by meta-analysis and evaluate the impact of food composition on 24-hour pharmacokinetics in pediatric kidney transplant recipients.

Integration of Genomic Sequencing Drives Therapeutic Targeting of PDGFRA in T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma.

Purpose: Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (T-LBL) have limited therapeutic options. Clinical use of genomic profiling provides an opportunity to identify targetable alterations to inform therapy.

Experimental Design: We describe a cohort of 14 pediatric patients with relapsed or refractory T-ALL enrolled on the Leukemia Precision-based Therapy (LEAP) Consortium trial (NCT02670525) and a patient with T-LBL, discovering alterations in platelet-derived growth factor receptor-α (PDGFRA) in 3 of these patients.