Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity.

Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs) have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC) to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs). We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell's ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell's ability to drive disease recurrence

Untold Perspectives: The Impact of the Closure of a Health Institution in a Black Community in North St. Louis County

Based on the literature of social determinants of health, health equity, and anchor institutions, it is evident that hospitals have a role to play in ensuring the health of their community. However, our understanding of the impact of hospital closures is limited, especially when it comes to Black communities. The purpose of this study is to examine the relationship of the closure of the Normandy Osteopathic Hospital to the social determinants of health—specifically access to care and economic stability as it relates to income and wealth generation—for a Black community in one near-North suburb of St. Louis. Ten individuals with a connection to the Normandy Osteopathic Hospital were interviewed using qualitative methods and an oral history protocol. Data was coded and analyzed using thematic analysis. Findings showed layers of disinvestment over time through national and local health care management decisions. Findings also showed that the hospital closure not only had an impact on access to health care, but also on community self-worth and economic wellbeing. As a result of these findings, policy implications and recommendations are explored

Adolescent Girls Empowerment Program (AGEP): Nutrition

Adolescence is a critical period in the lives of young people and potentially a time to reap lasting benefits from interventions that improve general, sexual, nutritional, and maternal and child health. The government of Zambia is committed to improving the nutritional status of adolescents and pregnant women and their children. Nonetheless, adolescent girls in Zambia remain at risk for macro- and micro-nutrient deficiencies that have deleterious effects on growth, development, and maternal and child health. The Adolescent Girls Empowerment Program (AGEP) nutritional curriculum, developed in partnership with PATH, was tailored to provide age-appropriate information and covered six sessions on nutrition. This brief summarizes the impact of the nutrition curriculum on nutrition outcomes of adolescents and their children one year after the AGEP program ended. The results of this rigorous randomized evaluation indicate that the AGEP nutrition training component with context-relevant participatory and interactive educational sessions did not improve adolescent or child nutritional outcomes

A Qualitative Exploration of the Functional, Social, and Emotional Impacts of the COVID-19 Pandemic on People Who Use Drugs

Since 2020, people who use drugs (PWUD) experienced heightened risks related to drug supply disruptions, contamination, overdose, social isolation, and increased stress. This study explored how the lives of PWUD changed in Philadelphia over a one-year period. Using semi-structured interviews with 20 participants in a Housing First, low-barrier medication for opioid use (MOUD) program in Philadelphia, the effects of the first year of the COVID-19 pandemic on the daily lives, resources, functioning, substance use, and treatment of PWUD were explored. Interviews were analyzed using a combination of directed and conventional content analysis. Six overarching themes emerged during data analysis: (1) response to the pandemic; (2) access to MOUD and support services; (3) substance use; (4) impacts on mental health, physical health, and daily functioning; (5) social network impacts; and (6) fulfillment of basic needs. Participants reported disruptions in every domain of life, challenges meeting their basic needs, and elevated risk for adverse events. MOUD service providers offset some risks and provided material supports, treatment, social interaction, and emotional support. These results highlight how there were significant disruptions to the lives of PWUD during the first year of the COVID-19 pandemic and identified critical areas for future intervention and policies

Nanosecond Laser Treatment for Age-Related Macular Degeneration Does Not Induce Focal Vision Loss or New Vessel Growth in the Retina

PURPOSE. Subthreshold, nanosecond pulsed laser treatment shows promise as a treatment for age-related macular degeneration (AMD)" however, the safety profile needs to be robustly examined. The aim of this study was to investigate the effects of laser treatment in humans and mice. METHODS. Patients with AMD were treated with nanosecond pulsed laser at subthreshold (no visible retinal effect) energy doses (0.15–0.45 mJ) and retinal sensitivity was assessed with microperimetry. Adult C57BL6J mice were treated at subthreshold (0.065 mJ) and suprathreshold (photoreceptor loss, 0.5 mJ) energy settings. The retinal and vascular responses were analyzed by fundus imaging, histologic assessment, and quantitative PCR. RESULTS. Microperimetry analysis showed laser treatment had no effect on retinal sensitivity under treated areas in patients 6 months to 7 years after treatment. In mice, subthreshold laser treatment induced RPE loss at 5 hours, and by 7 days the RPE had retiled. Fundus imaging showed reduced RPE pigmentation but no change in retinal thickness up to 3 months. Electron microscopy revealed changes in melanosomes in the RPE, but Bruch's membrane was intact across the laser regions. Histologic analysis showed normal vasculature and no neovascularization. Suprathreshold laser treatment did not induce changes in angiogenic genes associated with neovascularization. Instead pigment epithelium–derived factor, an antiangiogenic factor, was upregulated. CONCLUSIONS. In humans, low-energy, nanosecond pulsed laser treatment is not damaging to local retinal sensitivity. In mice, treatment does not damage Bruch's membrane or induce neovascularization, highlighting a reduced side effect profile of this nanosecond laser when used in a subthreshold manner

iSAW: Integrating Structure, Actors, and Water to Study Socio-Hydro-Ecological Systems

Urbanization, climate, and ecosystem change represent major challenges for managing water resources. Although water systems are complex, a need exists for a generalized representation of these systems to identify important components and linkages to guide scientific inquiry and aid water management. We developed an integrated Structure-Actor-Water framework (iSAW) to facilitate the understanding of and transitions to sustainable water systems. Our goal was to produce an interdisciplinary framework for water resources research that could address management challenges across scales (e.g., plot to region) and domains (e.g., water supply and quality, transitioning, and urban landscapes). The framework was designed to be generalizable across all human–environment systems, yet with sufficient detail and flexibility to be customized to specific cases. iSAW includes three major components: structure (natural, built, and social), actors (individual and organizational), and water (quality and quantity). Key linkages among these components include: (1) ecological/hydrologic processes, (2) ecosystem/geomorphic feedbacks, (3) planning, design, and policy, (4) perceptions, information, and experience, (5) resource access and risk, and (6) operational water use and management. We illustrate the flexibility and utility of the iSAW framework by applying it to two research and management problems: understanding urban water supply and demand in a changing climate and expanding use of green storm water infrastructure in a semi-arid environment. The applications demonstrate that a generalized conceptual model can identify important components and linkages in complex and diverse water systems and facilitate communication about those systems among researchers from diverse disciplines

SUSTAIN drilling at Surtsey volcano, Iceland, tracks hydrothermal and microbiological interactions in basalt 50 years after eruption

The 2017 Surtsey Underwater volcanic System for Thermophiles, Alteration processes and INnovative concretes (SUSTAIN) drilling project at Surtsey volcano, sponsored in part by the International Continental Scientific Drilling Program (ICDP), provides precise observations of the hydrothermal, geochemical, geomagnetic, and microbiological changes that have occurred in basaltic tephra and minor intrusions since explosive and effusive eruptions produced the oceanic island in 1963–1967. Two vertically cored boreholes, to 152 and 192 m below the surface, were drilled using filtered, UV-sterilized seawater circulating fluid to minimize microbial contamination. These cores parallel a 181 m core drilled in 1979. Introductory investigations indicate changes in material properties and whole-rock compositions over the past 38 years. A Surtsey subsurface observatory installed to 181 m in one vertical borehole holds incubation experiments that monitor in situ mineralogical and microbial alteration processes at 25–124 ∘C. A third cored borehole, inclined 55∘ in a 264∘ azimuthal direction to 354 m measured depth, provides further insights into eruption processes, including the presence of a diatreme that extends at least 100 m into the seafloor beneath the Surtur crater. The SUSTAIN project provides the first time-lapse drilling record into a very young oceanic basaltic volcano over a range of temperatures, 25–141 ∘C from 1979 to 2017, and subaerial and submarine hydrothermal fluid compositions. Rigorous procedures undertaken during the drilling operation protected the sensitive environment of the Surtsey Natural Preserve

Tamoxifen for the treatment of myeloproliferative neoplasms: a phase II clinical trial and exploratory analysis

Current therapies for myeloproliferative neoplasms (MPNs) improve symptoms but have limited effect on tumor size. In preclinical studies, tamoxifen restored normal apoptosis in mutated hematopoietic stem/progenitor cells (HSPCs). TAMARIN Phase-II, multicenter, single-arm clinical trial assessed tamoxifen’s safety and activity in patients with stable MPNs, no prior thrombotic events and mutated JAK2V617F, CALRins5 or CALRdel52 peripheral blood allele burden ≥20% (EudraCT 2015-005497-38). 38 patients were recruited over 112w and 32 completed 24w-treatment. The study’s A’herns success criteria were met as the primary outcome ( ≥ 50% reduction in mutant allele burden at 24w) was observed in 3/38 patients. Secondary outcomes included ≥25% reduction at 24w (5/38), ≥50% reduction at 12w (0/38), thrombotic events (2/38), toxicities, hematological response, proportion of patients in each IWG-MRT response category and ELN response criteria. As exploratory outcomes, baseline analysis of HSPC transcriptome segregates responders and non-responders, suggesting a predictive signature. In responder HSPCs, longitudinal analysis shows high baseline expression of JAK-STAT signaling and oxidative phosphorylation genes, which are downregulated by tamoxifen. We further demonstrate in preclinical studies that in JAK2V617F+ cells, 4-hydroxytamoxifen inhibits mitochondrial complex-I, activates integrated stress response and decreases pathogenic JAK2-signaling. These results warrant further investigation of tamoxifen in MPN, with careful consideration of thrombotic risk

Personalised Care Interprofessional Education Framework (PerCIE): Social prescribing placement curriculum document and guiding principles for undergraduate/postgraduate health and social care students

This Personalised Care Interprofessional Education (PerCIE) Framework has been designed to guide and support HEIs, and PEFs to enable health and social care students to learn about strengths-based approaches to health and wellbeing delivered by services that provide a social prescribing offer. It has been co-created by a network of experts from a broad range of professional backgrounds from seven universities (HEIs), Private Independent and Voluntary Organisations (PIVO sector also known as Voluntary Community Social Enterprise VCSE), National Social Prescribing Network Special Interest Group (SigSpn), Health Education England (Greater Manchester) and the NHS England (NHSe) Personalised Care team. It is underpinned by contemporary practice-based theory and evidence of impact from a range of successful UK projects. The PerCIE Framework is designed to enable universities to work in partnership with VCSE/PIVO partners to create collaborative and inclusive test beds for social action. It can help to support the generation of new socially connected learning opportunities that could provide rich and meaningful insight into health and health inequalities, our BAME communities and marginalised groups. It builds on and recognises the power of community resilience through asset-based working

Differences in the Tumor Microenvironment between African-American and European-American Breast Cancer Patients

Background: African-American breast cancer patients experience higher mortality rates than European-American patients despite having a lower incidence of the disease. We tested the hypothesis that intrinsic differences in the tumor biology may contribute to this cancer health disparity. Methods and Results: Using laser capture microdissection, we examined genome-wide mRNA expression specific to tumor epithelium and tumor stroma in 18 African-American and 17 European-American patients. Numerous genes were differentially expressed between these two patient groups and a two-gene signature in the tumor epithelium distinguished between them. To identify the biological processes in tumors that are different by race/ethnicity, Gene Ontology and disease association analyses were performed. Several biological processes were identified which may contribute to enhanced disease aggressiveness in African-American patients, including angiogenesis and chemotaxis. African-American tumors also contained a prominent interferon signature. The role of angiogenesis in the tumor biology of African-American