In the initial stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, a plethora of new serology tests were developed and introduced to the global market. Many were not evaluated rigorously, and there is a significant lack of concordance in results across methods. To enable meaningful clinical decisions to be made, robustly evaluated, quantitative serology methods are needed.
View Article and Find Full Text PDFWhen research is conducted from a Western paradigm alone, the findings and resultant policies often ignore Indigenous peoples' health practices and fail to align with their health care priorities. There is a need for decolonized approaches within qualitative health research to collaboratively identify intersecting reasons behind troubling health inequities and to integrate Indigenous knowledge into current health care services. We engaged with First Nations women to explore to what extent digital storytelling could be a feasible, acceptable, and meaningful research method to inform culturally safe health care services.
View Article and Find Full Text PDFBackground: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system that often leads to severe disability. Patients with highly active NMOSD have approximately a 10-times higher hospital inpatient admission rate compared with patients without NMOSD. Accurate assessments of the impact of NMOSD treatments on the burdens of illness require quantitative metrics of these burdens, including costs of care.
View Article and Find Full Text PDFBackground & Aims: Exclusive enteral nutrition (EEN) is used to treat pediatric Crohn's disease (CD), but therapeutic benefits are variable, and EEN can lead to microbial dysbiosis. Because of reported lower efficacy EEN is not routinely used to treat pediatric ulcerative colitis (UC). Inulin-type fructans (IN) beneficially modulate the gut microbiome and promote expansion of anti-inflammatory immune cells.
View Article and Find Full Text PDFAims: The aim of the Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) was to determine the optimal treatment for adults with a bicortical undisplaced or minimally displaced fracture of the waist of the scaphoid, comparing early surgical fixation with initial cast immobilization, with immediate fixation being offered to patients with nonunion.
Methods: A cost-effectiveness analysis was conducted to assess the relative merits of these forms of treatment. The differences in costs to the healthcare system and quality-adjusted life years (QALYs) of the patients over the one-year follow-up of the trial in the two treatment arms were estimated using regression analysis.
Pediatric palliative care (PPC) provides an extra layer of support for families caring for a child with complex heart disease as these patients often experience lifelong morbidities with frequent hospitalizations and risk of early mortality. PPC referral at the time of heart disease diagnosis provides early involvement in the disease trajectory, allowing PPC teams to longitudinally support patients and families with symptom management, complex medical decision-making, and advanced care planning. We analyzed 113 hospitalized pediatric patients with a primary diagnosis of heart disease and a PPC consult to identify timing of first PPC consultation in relation to diagnosis, complex chronic conditions (CCC), and death.
View Article and Find Full Text PDFBackground: Neuromyelitis optica spectrum disorder (NMOSD) is associated with various comorbidities, including non-autoimmune and autoimmune conditions. The burden and cost of illness for NMOSD are unclear, particularly in the context of comorbidities.
Methods: Claims data from IBM MarketScan Commercial and Medicare Supplemental Databases between 2014 and 2018 were analyzed.
Umbilical cord blood (UCB) transplantation is a potentially curative treatment for patients with refractory severe aplastic anaemia (SAA), but has historically been associated with delayed engraftment and high graft failure and mortality rates. We conducted a prospective phase 2 trial to assess outcome of an allogeneic transplant regimen that co-infused a single UCB unit with CD34 -selected cells from a haploidentical relative. Among 29 SAA patients [including 10 evolved to myelodysplastic syndrome (MDS)] who underwent the haplo cord transplantation (median age 20 years), 97% had neutrophil recovery (median 10 days), and 93% had platelet recovery (median 32 days).
View Article and Find Full Text PDFTransforming growth factor-beta (TGF-β) family proteins mediate many vital biological functions in growth, development and regulation of the immune system. TGF-β itself controls immune homeostasis and inflammation, including conversion of naïve CD4 T cells into Foxp3 regulatory T cells (Tregs) in the presence of interleukin-2 and T-cell receptor ligands. The helminth parasite Heligmosomoides polygyrus exploits this pathway through a structurally novel TGF-β mimic (Hp-TGM), which binds to mammalian TGF-β receptors and induces Tregs.
View Article and Find Full Text PDFM-type 28 (M28) Streptococcus pyogenes (group A Streptococcus [GAS]) strains are highly associated with life-threatening puerperal infections. Genome sequencing has revealed a large mobile genetic element, RD2, present in most M28 GAS isolates but not found widely in other serotypes. Previous studies have linked RD2 to the ability of M28 GAS to colonize the vaginal tract.
View Article and Find Full Text PDFPurpose Of Review: With the advent of precision medicine and demand for genomic testing information, we may question whether it is time to offer genetic testing to our patients with Parkinson disease (PD). This review updates the current genetic landscape of PD, describes what genetic testing may offer, provides strategies for evaluating whom to test, and provides resources for the busy clinician.
Recent Findings: Patients with PD and their relatives, in various settings, have expressed an interest in learning their PD genetic status; however, physicians may be hesitant to widely offer testing due to the perceived low clinical utility of PD genetic test results.
Immunol Cell Biol
September 2021
Immune homeostasis in the intestine is tightly controlled by FOXP3 regulatory T cells (Tregs), defects of which are linked to the development of chronic conditions, such as inflammatory bowel disease (IBD). As a mechanism of immune evasion, several species of intestinal parasites boost Treg activity. The parasite Heligmosomoides polygyrus is known to secrete a molecule (Hp-TGM) that mimics the ability of TGF-β to induce FOXP3 expression in CD4 T cells.
View Article and Find Full Text PDFEndometrial cancer (EC) is the leading female reproductive tract malignancy in developed countries. Currently, genome-wide association studies (GWAS) have identified 17 risk loci for EC. To identify novel EC-associated proteins, we used previously reported protein quantitative trait loci for 1434 plasma proteins as instruments to evaluate associations between genetically predicted circulating protein concentrations and EC risk.
View Article and Find Full Text PDFMetastasis, especially bone metastasis, is a major cause of cancer-related deaths, which is associated with long-term pain due to skeletal-related events and poor quality of life. Tumor cells alter the bone microenvironment through aberrant activation of osteoclasts and osteoblasts which induces bone osteolysis and release of growth factors leading to cancer growth. Though this phenomenon has been well characterized, bone-targeted therapies have shown little improvement in patient survival.
View Article and Find Full Text PDFObjectives: The primary objective of MATIS is to determine the efficacy of ruxolitinib (RUX) or fostamatinib (FOS) compared to standard of care (SOC) with respect to reducing the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia. Secondary objectives, at 14 and 28 days, are to: Determine the efficacy of RUX or FOS to reduce mortality Determine the efficacy of RUX or FOS to reduce the need for invasive ventilation or ECMO Determine the efficacy of RUX or FOS to reduce the need for non-invasive ventilation Determine the efficacy of RUX or FOS to reduce the proportion of participants suffering significant oxygen desaturation Determine the efficacy of RUX or FOS to reduce the need for renal replacement therapy Determine the efficacy of RUX and FOS to reduce the incidence of venous thromboembolism Determine the efficacy of RUX and FOS to reduce the severity of COVID-19 pneumonia [graded by a 9-point modified WHO Ordinal Scale* Determine the efficacy of RUX or FOS to reduce systemic inflammation Determine the efficacy of RUX or FOS to the incidence of renal impairment Determine the efficacy of RUX or FOS to reduce duration of hospital stay Evaluate the safety of RUX and FOS for treatment of COVID-19 pneumonia.
Trial Design: A multi-arm, multi-stage (3-arm parallel-group, 2-stage) randomised controlled trial that allocates participants 1:1:1 and tests for superiority in experimental arms versus standard of care.
Acute and chronic liver inflammation is driven by cytokine and chemokine release from various cell types in the liver. Here, we report that the induction of inflammatory mediators is associated with a yet undescribed upregulation of the metalloproteinase ADAM8 in different murine hepatitis models. We further show the importance of ADAM8 expression for the production of inflammatory mediators in cultured liver cells.
View Article and Find Full Text PDFBarriers to entering the field of invention have led to negative outcomes for individuals and for the economy. We built a vibrant middle class in the post-war era because we started to tear down many of the barriers that had kept women of all races and men of color from contributing their full talents. A quarter of the growth in aggregate output from 1960 to 2010 can be explained by improved allocation of talent.
View Article and Find Full Text PDFBrain health is neglected in public health, receiving attention after something goes wrong. Neuroplasticity research illustrates that preventive steps strengthen the brain's component systems; however, this information is not widely known. Actionable steps are needed to scale proven population-level interventions.
View Article and Find Full Text PDFAdult T cell leukaemia/lymphoma (ATL) arises from clonally expanded T cells that are infected with human T cell leukaemia virus type-1 (HTLV-1). Here, we show that ATL can be detected early in HTLV-1-carriers through quantification of T-cell receptor (TCR)Vβ subunit diversity on T-cells infected with HTLV-1 (CD3+ CCR4+ CD26- T-cells) using an 'oligoclonality index' (OCI-flow). We established a reference range for OCI-flow by analysing peripheral blood mononuclear cells (PBMCs) from HTLV-1-carriers who had not developed ATL in a median of 10.
View Article and Find Full Text PDFIntegrated developmental and elemental information in teeth provide a unique framework for documenting breastfeeding histories, physiological disruptions, and neurotoxicant exposure in humans and our primate relatives, including ancient hominins. Here we detail our method for detecting the consumption of mothers' milk and exploring health history through the use of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) mapping of sectioned nonhuman primate teeth. Calcium-normalized barium and lead concentrations in tooth enamel and dentine may reflect milk and formula consumption with minimal modification during subsequent tooth mineralization, particularly in dentine.
View Article and Find Full Text PDFMost US medical schools have 3 primary missions: education, research, and clinical service. Recently there have been calls for a fourth primary mission focused on improving health in their surrounding communities. To date, few medical schools have done so.
View Article and Find Full Text PDFPurpose Of Review: To describe current practices and attitudes about genetic testing for Parkinson's disease (PD) among neurologists, highlight the changing scene of genetic testing for PD, and provide guidance on facilitating PD genetic testing in a clinical practice.
Recent Findings: Since the 1990s, researchers have discovered several major gene variants contributing to PD etiology. A large body of literature now exists supporting the frequency of these variants in different populations and their effects on phenotype and clinical course.