Designing and carrying out a controlled human infection (CHI) model for hepatitis C virus (HCV) is critical for vaccine development. However, key considerations for a CHI model protocol include understanding of the earliest viral-host kinetic events during the acute phase and susceptibility of the viral isolate under consideration for use in the CHI model to antiviral treatment before any infections in human volunteers can take place. Humanized mouse models lack adaptive immune responses but provide a unique opportunity to obtain quantitative understanding of early HCV kinetics and develop mathematical models to further understand viral and innate immune response dynamics during acute HCV infection.
View Article and Find Full Text PDFBackground: Limited research on food systems and food insecurity (FI) following disasters finds contextual differences in post-disaster food systems that shape dimensions of FI. Measurement limitations make it difficult to address FI and develop effective practices for disaster-affected communities.
Objective: To develop, validate, and test a Disaster Food Security Framework (DFSF).
Periosteal stem and progenitor cells (PSPCs) are major contributors to bone maintenance and repair. Deciphering the molecular mechanisms that regulate their function is crucial for the successful generation and application of future therapeutics. Here, we pinpoint Hox transcription factors as necessary and sufficient for periosteal stem cell function.
View Article and Find Full Text PDFWildfires are a global crisis, but current fire models fail to capture vegetation response to changing climate. With drought and elevated temperature increasing the importance of vegetation dynamics to fire behavior, and the advent of next generation models capable of capturing increasingly complex physical processes, we provide a renewed focus on representation of woody vegetation in fire models. Currently, the most advanced representations of fire behavior and biophysical fire effects are found in distinct classes of fine-scale models and do not capture variation in live fuel (i.
View Article and Find Full Text PDFWe document trends in food security up to one full year after the onset of the COVID-19 pandemic in four African countries. Using household-level data collected by the World Bank, we highlight differences over time amid the pandemic, between rural and urban areas, and between female-headed and male-headed households within Burkina Faso, Ethiopia, Malawi, and Nigeria. We first observe a sharp increase in food insecurity during the early months of the pandemic with a subsequent gradual decline.
View Article and Find Full Text PDFInflammatory and neuropathic-like components underlie rheumatoid arthritis (RA)-associated pain, and lysophosphatidic acid (LPA) is linked to both joint inflammation in RA patients and to neuropathic pain. Thus, we investigated a role for LPA signalling using the collagen antibody-induced arthritis (CAIA) model. Pain-like behavior during the inflammatory phase and the late, neuropathic-like phase of CAIA was reversed by a neutralizing antibody generated against LPA and by an LPA receptor inhibitor, but joint inflammation was not affected.
View Article and Find Full Text PDFTissue injury leads to the well-orchestrated mobilization of systemic and local innate and adaptive immune cells. During aging, immune cell recruitment is dysregulated, resulting in an aberrant inflammatory response that is detrimental for successful healing. Here, we precisely define the systemic and local immune cell response after femur fracture in young and aging mice and identify increased toll-like receptor signaling as a potential culprit for the abnormal immune cell recruitment observed in aging animals.
View Article and Find Full Text PDFBackground: The coronavirus disease 2019 (COVID-19) pandemic profoundly affected food systems including food security. Understanding how the COVID-19 pandemic impacted food security is important to provide support and identify long-term impacts and needs.
Objective: The National Food Access and COVID research Team (NFACT) was formed to assess food security over different US study sites throughout the pandemic, using common instruments and measurements.
Adult bone regeneration is orchestrated by the precise actions of osteoprogenitor cells (OPCs). However, the mechanisms by which OPC proliferation and differentiation are linked and thereby regulated are yet to be defined. Here, we present evidence that during intramembranous bone formation OPC proliferation is controlled by Notch signaling, while differentiation is initiated by activation of canonical Wnt signaling.
View Article and Find Full Text PDFAging tissues undergo a progressive decline in regenerative potential. This decline in regenerative responsiveness has been attributed to changes in tissue-specific stem cells and their niches. In bone, aged skeletal stem/progenitor cell dysfunction is characterized by decreased frequency and impaired osteogenic differentiation potential.
View Article and Find Full Text PDFThe emergence of SARS-CoV-2 and attempts to limit its spread have resulted in a contraction of the global economy. Here we document the socioeconomic impacts of the pandemic among households, adults and children in low-income countries. To do so, we rely on longitudinal household survey data from Ethiopia, Malawi, Nigeria and Uganda, originating from pre-COVID-19 face-to-face household surveys plus phone surveys implemented during the pandemic.
View Article and Find Full Text PDFAn amendment to this paper has been published and can be accessed via a link at the top of the paper.
View Article and Find Full Text PDFSelective serotonin reuptake inhibitors (SSRIs) are one of the most commonly prescribed antidepressants worldwide and recent data show significant impairment of fracture healing after treatment with the SSRI fluoxetine in mice. Here, we provide evidence that the negative effects of SSRIs can be overcome by administration of the beta-blocker propranolol at the time of fracture. First, in vitro experiments established that propranolol does not affect osteogenic differentiation.
View Article and Find Full Text PDFWe previously showed that KLF4, a gene highly expressed in murine prostate stem cells, blocks the progression of indolent intraepithelial prostatic lesions into aggressive and rapidly growing tumors. Here, we show that the anti-tumorigenic effect of KLF4 extends to PC3 human prostate cancer cells growing in the bone. We compared KLF4 null cells with cells transduced with a DOX-inducible KLF4 expression system, and find KLF4 function inhibits PC3 growth in monolayer and soft agar cultures.
View Article and Find Full Text PDFObstetric violence refers to the mistreatment of women in pregnancy and childbirth care by their health providers. It is linked to poor quality of care, lack of trust in health systems, and adverse maternal and neonatal outcomes. Evidence of interventions to reduce and prevent obstetric violence is limited.
View Article and Find Full Text PDFHox genes are evolutionarily conserved transcription factors that during embryonic development function as master regulators of positional identity. In postnatal life, the function of Hox proteins is less clear: Hox genes are expressed during tissue repair, but in this context their function(s) are largely unknown. Here we show that Hox genes are expressed in periosteal stem/progenitor cells in a distribution similar to that during embryonic development.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
April 2019
Aging is associated with impaired tissue regeneration. Stem cell number and function have been identified as potential culprits. We first demonstrate a direct correlation between stem cell number and time to bone fracture union in a human patient cohort.
View Article and Find Full Text PDFThis paper reports a qualitative study that explored the meanings of interprofessional education (IPE) by comparing and contrasting educational leaders' perceptions with educational policy documents at an academic health professions education institution in Scandinavia. The study used Goffman's frame analysis to identify two frames of IPE by illuminating issues related to the definition, rationale, and presentation of IPE. A directed content analysis to identify these three aspects of IPE was conducted on semi-structured interviews with nine educational leaders who were overseeing the development of IPE, as well as on the institution's regulatory IPE documentation.
View Article and Find Full Text PDFIntroduction: Aminocaproic acid is approved as an anti-fibrinolytic for use in joint replacement and spinal fusion surgeries to limit perioperative blood loss. Previous animal studies have demonstrated a pro-osteogenic effect of aminocaproic acid in spine fusion models. Here, we tested if aminocaproic acid enhances appendicular bone healing and we sought to uncover the effect of aminocaproic acid on osteoprogenitor cells (OPCs) during bone regeneration.
View Article and Find Full Text PDFUnderstanding usual care is important to reduce health disparities and improve the dissemination of evidence-based practices for youth (ages 7-22 years) with autism spectrum disorder (ASD). A barrier to describing "usual ASD care" is the lack of a common vocabulary and inventory of the practices used by a diverse provider field. To address this barrier, we gathered input from expert providers to develop an inventory of usual care practices and assess expert familiarity and perceptions of these practices as interventions for anxiety, externalizing, and social difficulties in ASD.
View Article and Find Full Text PDFApproximately 400,000 adolescents give birth in the USA annually. Although one-half experience depressive symptoms, less than 25% comply with referrals for depression evaluation and treatment. The current study tested the effectiveness of an Internet-based depression intervention on seeking depression treatment.
View Article and Find Full Text PDFEcto-5'-nucleotidase (CD73) generates adenosine, an osteoblast activator and key regulator of skeletal growth. It is unknown, however, if CD73 regulates osteogenic differentiation during fracture healing in adulthood, and in particular how CD73 activity regulates intramembranous bone repair in the elderly. Monocortical tibial defects were created in 46-52-week-old wild type (WT) and CD73 knock-out mice (CD73) mice.
View Article and Find Full Text PDFBackground: The mission of undergraduate medical education leaders is to strive towards the enhancement of quality of medical education and health care. The aim of this qualitative study is, with the help of critical perspectives, to contribute to the research area of undergraduate medical education leaders and their identity formation; how can the identity of undergraduate medical education leaders be defined and further explored from a power perspective?
Methods: In this explorative study, 14 educational leaders at a medical programme in Scandinavia were interviewed through semi-structured interviews. The data was analysed through Moustakas' structured, phenomenological analysis approach and then pattern matched with Gee's power-based identity model.
Chronic use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression has been linked to osteoporosis. In this study, we investigated the effect of chronic SSRI use on fracture healing in two murine models of bone regeneration. First, we performed a comprehensive analysis of endochondral bone healing in a femur fracture model.
View Article and Find Full Text PDF