Expression of Ifnlr1 on intestinal epithelial cells is critical to the antiviral effects of IFN-lambda against norovirus and reovirus

Lambda interferon (IFN-λ) has potent antiviral effects against multiple enteric viral pathogens, including norovirus and rotavirus, in both preventing and curing infection. Because the intestine includes a diverse array of cell types, however, the cell(s) upon which IFN-λ acts to exert its antiviral effects is unclear. Here, we sought to identify IFN-λ-responsive cells by generation of mice with lineage-specific deletion of the receptor for IFN-λ, Ifnlr1. We found that expression of IFNLR1 on intestinal epithelial cells (IECs) in the small intestine and colon is required for enteric IFN-λ antiviral activity. IEC Ifnlr1 expression also determines the efficacy of IFN-λ in resolving persistent murine norovirus (MNoV) infection and regulates fecal shedding and viral titers in tissue. Thus, the expression of Ifnlr1 by IECs is necessary for the response to both endogenous and exogenous IFN-λ. We further demonstrate that IEC Ifnlr1 expression is required for the sterilizing innate immune effects of IFN-λ by extending these findings in Rag1-deficient mice. Finally, we assessed whether our findings pertained to multiple viral pathogens by infecting mice specifically lacking IEC Ifnlr1 expression with reovirus. These mice phenocopied Ifnlr1-null animals, exhibiting increased intestinal tissue titers and enhanced reovirus fecal shedding. Thus, IECs are the critical cell type responding to IFN-λ to control multiple enteric viruses. This is the first genetic evidence that supports an essential role for IECs in IFN-λ-mediated control of enteric viral infection, and these findings provide insight into the mechanism of IFN-λ-mediated antiviral activity. IMPORTANCE Human noroviruses (HNoVs) are the leading cause of epidemic gastroenteritis worldwide. Type III interferons (IFN-λ) control enteric viral infections in the gut and have been shown to cure mouse norovirus, a small-animal model for HNoVs. Using a genetic approach with conditional knockout mice, we identified IECs as the dominant IFN-λ-responsive cells in control of enteric virus infection in vivo. Upon murine norovirus or reovirus infection, Ifnlr1 depletion in IECs largely recapitulated the phenotype seen in Ifnlr1(−/−) mice of higher intestinal tissue viral titers and increased viral shedding in the stool. Moreover, IFN-λ-mediated sterilizing immunity against murine norovirus requires the capacity of IECs to respond to IFN-λ. These findings clarify the mechanism of action of this cytokine and emphasize the therapeutic potential of IFN-λ for treating mucosal viral infections

Toward the Ultrasonic Sensing of Organic Carbon in Seagrass-Bearing Sediments

Ten percent of all organic carbon (Corg) absorbed by the ocean each year is stored in seagrass-bearing sediments. The preservation of these carbon stores is considered a vital method to mitigate climate change. Seagrass-bearing sediments have been correlated with sediment geophysical properties yet have not been related to sediment acoustic properties. For this purpose, sediment cores were collected from a Thalassia testudinum seagrass meadow in South Texas, USA, where geophysical, acoustical, and Corg properties were measured. It is hypothesized that when deposits of Corg adsorb onto mineral surfaces and are stored in pore spaces, compliant layers between grain contacts and the formation of an organic-rich suspension reduce sediment stiffness. Results from this seagrass meadow demonstrated a strong correlation between sediment P wave modulus and Corg and show promise toward the development of an in situ ultrasonic sediment probe to more rapidly quantify and monitor seagrass carbon stores

Motivational Interviewing to Improve Self-Care for Patients with Chronic Heart Failure: MITI-HF Randomized Controlled Trial

OBJECTIVE: The purpose of this study was to test the efficacy of a tailored motivational interviewing (MI) intervention versus usual care for improving HF self-care behaviors, physical HF symptoms and quality of life. METHODS: This is a single-center, randomized controlled trial. Participants were enrolled in the hospital. Immediately after discharge, those in the intervention group received a single home visit and 3-4 follow-up phone calls by a nurse over 90 days. RESULTS: A total of 67 participants completed the study (mean age 62±12.8 years), of which 54% were African American, 30% were female, 84% had class III/IV symptoms, and 63% were educated at a high school level or less. There were no differences between the groups in self-care maintenance, self-care confidence, physical HF symptoms, or quality of life at 90 days. CONCLUSION: Patients who received the MI intervention had significant and clinically meaningful improvements in HF self-care maintenance over 90 days that exceeded that of usual care. PRACTICE IMPLICATIONS: These data support the use of a nurse-led MI intervention for improving HF self-care. Identifying methods to improve HF self-care may lead to improved clinical outcomes

Highly efficient transfection of human induced pluripotent stem cells using magnetic nanoparticles.

PurposeThe delivery of transgenes into human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) represents an important tool in cardiac regeneration with potential for clinical applications. Gene transfection is more difficult, however, for hiPSCs and hiPSC-CMs than for somatic cells. Despite improvements in transfection and transduction, the efficiency, cytotoxicity, safety, and cost of these methods remain unsatisfactory. The objective of this study is to examine gene transfection in hiPSCs and hiPSC-CMs using magnetic nanoparticles (NPs).MethodsMagnetic NPs are unique transfection reagents that form complexes with nucleic acids by ionic interaction. The particles, loaded with nucleic acids, can be guided by a magnetic field to allow their concentration onto the surface of the cell membrane. Subsequent uptake of the loaded particles by the cells allows for high efficiency transfection of the cells with nucleic acids. We developed a new method using magnetic NPs to transfect hiPSCs and hiPSC-CMs. HiPSCs and hiPSC-CMs were cultured and analyzed using confocal microscopy, flow cytometry, and patch clamp recordings to quantify the transfection efficiency and cellular function.ResultsWe compared the transfection efficiency of hiPSCs with that of human embryonic kidney (HEK 293) cells. We observed that the average efficiency in hiPSCs was 43%±2% compared to 62%±4% in HEK 293 cells. Further analysis of the transfected hiPSCs showed that the differentiation of hiPSCs to hiPSC-CMs was not altered by NPs. Finally, robust transfection of hiPSC-CMs with an efficiency of 18%±2% was obtained.ConclusionThe difficult-to-transfect hiPSCs and hiPSC-CMs were efficiently transfected using magnetic NPs. Our study offers a novel approach for transfection of hiPSCs and hiPSC-CMs without the need for viral vector generation

Predictors of Objectively Measured Medication Nonadherence in Adults With Heart Failure

Background—Medication nonadherence rates are high. The factors predicting nonadherence in heart failure remain unclear. Methods and Results—A sample of 202 adults with heart failure was enrolled from the northeastern United States and followed for 6 months. Specific aims were to describe the types of objectively measured medication adherence (eg, taking, timing, dosing, drug holidays) and to identify contributors to nonadherence 6 months after enrollment. Latent growth mixture modeling was used to identify distinct trajectories of adherence. Indicators of the 5 World Health Organization dimensions of adherence (socioeconomic, condition, therapy, patient, and healthcare system) were tested to identify contributors to nonadherence. Two distinct trajectories were identified and labeled persistent adherence (77.8%) and steep decline (22.3%). Three contributors to the steep decline in adherence were identified. Participants with lapses in attention (adjusted OR, 2.65; P=0.023), those with excessive daytime sleepiness (OR, 2.51; P=0.037), and those with ≥2 medication dosings per day (OR, 2.59; P=0.016) were more likely to have a steep decline in adherence over time than to have persistent adherence. Conclusions—Two distinct patterns of adherence were identified. Three potentially modifiable contributors to nonadherence have been identified

Application of acoustical remote sensing techniques for ecosystem monitoring of a seagrass meadow

Seagrasses provide a multitude of ecosystem services and serve as important organic carbon stores. However, seagrass habitats are declining worldwide, threatened by global climate change and regional shifts in water quality. Acoustical methods have been applied to assess changes in oxygen production of seagrass meadows since sound propagation is sensitive to the presence of bubbles, which exist both within the plant tissue and freely floating the water as byproducts of photosynthesis. This work applies acoustic remote sensing techniques to characterize two different regions of a seagrass meadow: a densely vegetated meadow of Thalassia testudinum and a sandy region sparsely populated by isolated stands of T. testudinum. A Bayesian approach is applied to estimate the posterior probability distributions of the unknown model parameters. The sensitivity of sound to the void fraction of gas present in the seagrass meadow was established by the narrow marginal probability distributions that provided distinct estimates of the void fraction between the two sites. The absolute values of the estimated void fractions are biased by limitations in the forward model, which does not capture the full complexity of the seagrass environment. Nevertheless, the results demonstrate the potential use of acoustical methods to remotely sense seagrass health and density

Inter-seasonal comparison of acoustic propagation in a Thalassia testudinum seagrass meadow in a shallow sub-tropical lagoon

Acoustic propagation measurements were collected in a seagrass meadow in a shallow lagoon for periods of over 65 h in winter and 93 h in summer. A bottom-deployed sound source transmitted chirps (0.1–100 kHz) every 10 min that were received on a four-receiver horizontal hydrophone array. Oceanographic probes measured various environmental parameters. Daytime broadband acoustic attenuation was 2.4 dB greater in summer than winter, and the median received acoustic energy levels were 8.4 dB lower in summer compared to winter. These differences were attributed in part to seasonal changes in photosynthesis bubble production and above-ground seagrass biomass

Comparison of industry payments to psychiatrists and psychiatric advanced practice clinicians in the USA, 2021: A cross-sectional study

Objectives: To compare industry payment patterns among US psychiatrists and psychiatric advanced practice clinicians (APCs) and determine how scope of practice laws has influenced these patterns. Design: Cross-sectional study. Setting: This study used the publicly available US Centers for Medicare and Medicaid Services Sunshine Act Open Payment database and the National Plan and Provider Enumeration System (NPPES) database for the year 2021. Participants: All psychiatrists and psychiatric APCs (subdivided into nurse practitioners (NPs) and clinical nurse specialists (CNSs)) included in either database. Primary and secondary outcome measures: Number and percentage of clinicians receiving industry payments and value of payments received. Total payments and number of transactions by type of payment, payment source and clinician type were also evaluated. Results: A total of 85 053 psychiatric clinicians (61 011 psychiatrists (71.7%), 21 895 NPs (25.7%), 2147 CNSs (2.5%)) were reviewed; 16 240 (26.6%) psychiatrists received non-research payment from industry, compared with 10 802 (49.3%) NPs and 231 (10.7%) CNSs (p United States Dollars (US) $) 100 (33.9$ 1000 (5.3% vs 4.1%; IRR, 1.29 (1.20 to 1.38); p US$ 10 000 (0.4% vs 1.0%; IRR, 0.39 (0.31 to 0.49); p Conclusions: Psychiatric NPs were nearly two times as likely to receive industry payments as psychiatrists, while psychiatric CNSs were less than half as likely to receive payment. Stricter scope of practice laws increases the likelihood of psychiatric NPs receiving payment, the opposite of what was found in a recent specialty agnostic study.</p