Examining the Role of Race in End-of-Life Care in the Intensive Care Unit: A Single-Center Observational Study.

Background: Prior studies have shown variation in the intensity of end-of-life care in intensive care units (ICUs) among patients of different races. Objective: We sought to identify variation in the levels of care at the end of life in the ICU and to assess for any association with race and ethnicity. Design: An observational, retrospective cohort study. Settings: A tertiary care center in Boston, MA. Participants: All critically ill patients admitted to medical and surgical ICUs between June 2019 and December 2020. Exposure: Self-identified race and ethnicity. Main Outcome and Measure: The primary outcome was death. Secondary outcomes included "code status," markers of intensity of care, consultation by the Palliative care service, and consultation by the Ethics service. Results: A total of 9083 ICU patient encounters were analyzed. One thousand two hundred fifty-nine patients (14%) died in the ICU; the mean age of patients was 64 years (standard deviation 16.8), and 44% of patients were women. A large number of decedents (22.7%) did not have their race identified. These patients had a high rate of interventions at death. Code status varied by race, with more White patients designated as "Comfort Measures Only" (CMO) (74%) whereas more Black patients were designated as "Do Not Resuscitate/Do Not Intubate (DNR/DNI) and DNR/ok to intubate" (12.1% and 15.7%) at the end of life; after adjustment for age and severity of illness, there were no statistical differences by race for the use of the CMO code status. Use of dialysis at the end of life varied by self-identified race. Specifically, Black and Unknown patients were more likely to receive renal replacement therapy, even after adjustment for age and severity of illness (24% and 20%, p = 0.003). Conclusions: Our data describe a gap in identification of race and ethnicity, as well as differences at the end of life in the ICU, especially with respect to code status and certain markers of intensity.

Oxygen saturation targets for adults with acute hypoxemia in low and lower-middle income countries: a scoping review with analysis of contextual factors.

Knowing the target oxygen saturation (SpO2) range that results in the best outcomes for acutely hypoxemic adults is important for clinical care, training, and research in low-income and lower-middle income countries (collectively LMICs). The evidence we have for SpO2 targets emanates from high-income countries (HICs), and therefore may miss important contextual factors for LMIC settings. Furthermore, the evidence from HICs is mixed, amplifying the importance of specific circumstances. For this literature review and analysis, we considered SpO2 targets used in previous trials, international and national society guidelines, and direct trial evidence comparing outcomes using different SpO2 ranges (all from HICs). We also considered contextual factors, including emerging data on pulse oximetry performance in different skin pigmentation ranges, the risk of depleting oxygen resources in LMIC settings, the lack of access to arterial blood gases that necessitates consideration of the subpopulation of hypoxemic patients who are also hypercapnic, and the impact of altitude on median SpO2 values. This process of integrating prior study protocols, society guidelines, available evidence, and contextual factors is potentially useful for the development of other clinical guidelines for LMIC settings. We suggest that a goal SpO2 range of 90-94% is reasonable, using high-performing pulse oximeters. Answering context-specific research questions, such as an optimal SpO2 target range in LMIC contexts, is critical for advancing equity in clinical outcomes globally.

Patient experiences and perspectives on hypertension at a major referral hospital in rural southwestern Uganda: a qualitative analysis.

OBJECTIVES: Novel care models are needed to address the large burden of hypertension globally. We aimed to explore how patients in rural Uganda experience and perceive hypertension in order to understand factors that may inform development of a patient-centred care model for hypertension management in this setting. DESIGN: We conducted one-time, in-depth qualitative interviews focusing on participants' experiences and perceptions of the meaning and management of hypertension. SETTING: Outpatient clinic at Mbarara Regional Referral Hospital in Uganda. PARTICIPANTS: We enrolled patients who had hypertension and had used antihypertensive medication for at least 1 month. We used purposive sampling to recruit 30 participants with similar representation by gender and by absence or presence of comorbid conditions. RESULTS: Participants had been diagnosed and initiated care at various clinical stages of hypertension, which impacted their understanding of hypertension. Several participants saw hypertension as a chronic disease that can lead to complications if not controlled, while others attributed symptoms typically associated with other diseases to hypertension. Participants described inconsistent access to antihypertensive medications and difficulty with transport to the clinic (time needed and expense) as the major barriers to access to care. Initiation and maintenance of care were facilitated by family support and ready access to health facilities. Many participants identified an understanding of the important lifestyle and dietary changes required to control hypertension. CONCLUSIONS: Patients with hypertension in rural Uganda demonstrated a varied understanding and experience with hypertension. Interventions leveraging family support may help with patient education and clinical management. Integration of patient perspectives into the care model, patient-centred care, may serve as a successful model for hypertension and potentially delivery of care for other non-communicable diseases in Uganda and other similar resource-limited settings.

Cryptic glucocorticoid receptor-binding sites pervade genomic NF-κB response elements.

Glucocorticoids (GCs) are potent repressors of NF-κB activity, making them a preferred choice for treatment of inflammation-driven conditions. Despite the widespread use of GCs in the clinic, current models are inadequate to explain the role of the glucocorticoid receptor (GR) within this critical signaling pathway. GR binding directly to NF-κB itself-tethering in a DNA binding-independent manner-represents the standing model of how GCs inhibit NF-κB-driven transcription. We demonstrate that direct binding of GR to genomic NF-κB response elements (κBREs) mediates GR-driven repression of inflammatory gene expression. We report five crystal structures and solution NMR data of GR DBD-κBRE complexes, which reveal that GR recognizes a cryptic response element between the binding footprints of NF-κB subunits within κBREs. These cryptic sequences exhibit high sequence and functional conservation, suggesting that GR binding to κBREs is an evolutionarily conserved mechanism of controlling the inflammatory response.

Iron Oxide Nanoparticles Stimulates Extra-Cellular Matrix Production in Cellular Spheroids.

Nanotechnologies have been integrated into drug delivery, and non-invasive imaging applications, into nanostructured scaffolds for the manipulation of cells. The objective of this work was to determine how the physico-chemical properties of magnetic nanoparticles (MNPs) and their spatial distribution into cellular spheroids stimulated cells to produce an extracellular matrix (ECM). The MNP concentration (0.03 mg/mL, 0.1 mg/mL and 0.3 mg/mL), type (magnetoferritin), shape (nanorod-85 nm × 425 nm) and incorporation method were studied to determine each of their effects on the specific stimulation of four ECM proteins (collagen I, collagen IV, elastin and fibronectin) in primary rat aortic smooth muscle cell. Results demonstrated that as MNP concentration increased there was up to a 6.32-fold increase in collagen production over no MNP samples. Semi-quantitative Immunohistochemistry (IHC) results demonstrated that MNP type had the greatest influence on elastin production with a 56.28% positive area stain compared to controls and MNP shape favored elastin stimulation with a 50.19% positive area stain. Finally, there are no adverse effects of MNPs on cellular contractile ability. This study provides insight on the stimulation of ECM production in cells and tissues, which is important because it plays a critical role in regulating cellular functions.

Community Health Workers and the Management of Noncommunicable Diseases Among Rural Health Clinics in Limpopo Province, South Africa: A Pilot Study.

South Africa's rise in noncommunicable diseases (NCDs) and health care provider shortages has generated the need for community health workers (CHWs) in rural areas. However, roles and interactions with clinic staff are not well understood. Interviews with health care workers at community clinics in Limpopo Province revealed common themes, including resource scarcity, clinic-patient partnerships, management of NCDs, and collaboration between professionals. The data did not support CHW-physician interactions, necessitating further research to describe these practices and to evaluate CHWs' impact on patient outcomes. The CHW involvement in rural clinics is essential to patient-clinic partnerships and may help close treatment gaps in resource-poor areas.

Longitudinal Stretching for Maturation of Vascular Tissues Using Magnetic Forces.

Cellular spheroids were studied to determine their use as "bioinks" in the biofabrication of tissue engineered constructs. Specifically, magnetic forces were used to mediate the cyclic longitudinal stretching of tissues composed of Janus magnetic cellular spheroids (JMCSs), as part of a post-processing method for enhancing the deposition and mechanical properties of an extracellular matrix (ECM). The purpose was to accelerate the conventional tissue maturation process via novel post-processing techniques that accelerate the functional, structural, and mechanical mimicking of native tissues. The results of a forty-day study of JMCSs indicated an expression of collagen I, collagen IV, elastin, and fibronectin, which are important vascular ECM proteins. Most notably, the subsequent exposure of fused tissue sheets composed of JMCSs to magnetic forces did not hinder the production of these key proteins. Quantitative results demonstrate that cyclic longitudinal stretching of the tissue sheets mediated by these magnetic forces increased the Young's modulus and induced collagen fiber alignment over a seven day period, when compared to statically conditioned controls. Specifically, the elastin and collagen content of these dynamically-conditioned sheets were 35- and three-fold greater, respectively, at seven days compared to the statically-conditioned controls at three days. These findings indicate the potential of using magnetic forces in tissue maturation, specifically through the cyclic longitudinal stretching of tissues.

Biological magnetic cellular spheroids as building blocks for tissue engineering.

Magnetic nanoparticles (MNPs), primarily iron oxide nanoparticles, have been incorporated into cellular spheroids to allow for magnetic manipulation into desired shapes, patterns and 3-D tissue constructs using magnetic forces. However, the direct and long-term interaction of iron oxide nanoparticles with cells and biological systems can induce adverse effects on cell viability, phenotype and function, and remain a critical concern. Here we report the preparation of biological magnetic cellular spheroids containing magnetoferritin, a biological MNP, capable of serving as a biological alternative to iron oxide magnetic cellular spheroids as tissue engineered building blocks. Magnetoferritin NPs were incorporated into 3-D cellular spheroids with no adverse effects on cell viability up to 1 week. Additionally, cellular spheroids containing magnetoferritin NPs were magnetically patterned and fused into a tissue ring to demonstrate its potential for tissue engineering applications. These results present a biological approach that can serve as an alternative to the commonly used iron oxide magnetic cellular spheroids, which often require complex surface modifications of iron oxide NPs to reduce the adverse effects on cells.

Optical sensing by transforming chromophoric silver clusters in DNA nanoreactors.

Bifunctional DNA oligonucleotides serve as templates for chromophoric silver clusters and as recognition sites for target DNA strands, and communication between these two components is the basis of an oligonucleotide sensor. Few-atom silver clusters exhibit distinct electronic spectra spanning the visible and near-infrared region, and they are selectively synthesized by varying the base sequence of the DNA template. In these studies, a 16-base cluster template is adjoined with a 12-base sequence complementary to the target analyte, and hybridization induces structural changes in the composite sensor that direct the conversion between two spectrally and stoichiometrically distinct clusters. Without its complement, the sensor strand selectively harbors ~7 Ag atoms that absorb at 400 nm and fold the DNA host. Upon association of the target with its recognition site, the sensor strand opens to expose the cluster template that has the binding site for ~11 Ag atoms, and absorption at 720 nm with relatively strong emission develops in lieu of the violet absorption. Variations in the length and composition of the recognition site and the cluster template indicate that these types of dual-component sensors provide a general platform for near-infrared-based detection of oligonucleotides in challenging biological environments.