Low-dose ionizing radiation promotes motor recovery and brain rewiring by resolving inflammatory response after brain injury and stroke.

Traumatic brain injury (TBI) and stroke share a common pathophysiology that worsens over time due to secondary tissue injury caused by sustained inflammatory response. However, studies on pharmacological interventions targeting the complex secondary injury cascade have failed to show efficacy. Here, we demonstrated that low-dose ionizing radiation (LDIR) reduced lesion size and reversed motor deficits after TBI and photothrombotic stroke. Magnetic resonance imaging demonstrated significant reduction of infarct volume in LDIR-treated mice after stroke. Systems-level transcriptomic analysis showed that genes upregulated in LDIR-treated stoke mice were enriched in pathways associated with inflammatory and immune response involving microglia. LDIR induced upregulation of anti-inflammatory- and phagocytosis-related genes, and downregulation of key pro-inflammatory cytokine production. These findings were validated by live-cell assays, in which microglia exhibited higher chemotactic and phagocytic capacities after LDIR. We observed substantial microglial clustering at the injury site, glial scar clearance and reversal of motor deficits after stroke. Cortical microglia/macrophages depletion completely abolished the beneficial effect of LDIR on motor function recovery in stroke mice. LDIR promoted axonal projections (brain rewiring) in motor cortex and recovery of brain activity detected by electroencephalography recordings months after stroke. LDIR treatment delayed by 8 h post-injury still maintained full therapeutic effects on motor recovery, indicating that LDIR is a promising therapeutic strategy for TBI and stroke.

Interferon Beta-1α ring prophylaxis to reduce household transmission of SARS-CoV-2

ImportanceEvidence suggests that early, robust type 1 interferon responses to SARS-CoV-2 are critical determinants for COVID-19 disease outcomes, accelerating viral clearance and limiting viral shedding. ObjectiveWe undertook a ring prophylaxis study to determine whether pegylated IFN{beta}-1 could reduce SARS-CoV-2 household transmission. DesignA cluster randomized clinical trial of pegylated IFN{beta}-1 conducted in Santiago, Chile. Recruitment was conducted between December 4th 2020, and 31st May 2021, with the last follow-up completed June 29th 2021. SettingThe study was conducted across 341 households in the metropolitan area of Santiago, Chile. ParticipantsIndex cases were identified from databases of those with confirmed SARS-CoV-2 from COVID-19 clinics and emergency room visits in Santiago, Chile. 5,154 index cases were assessed for eligibility, 1,372 index cases were invited to participate, and 341 index cases and their household contacts (n = 831) were enrolled in the study. InterventionHouseholds were cluster randomized to receive 125{micro}g subcutaneous pegylated IFN{beta}-1 (n = 172 households, 607 participants), or standard care (n = 169 households, 565 participants). Main Outcome(s) and Measure(s)Frequentist and Bayesian analyses were undertaken to determine the effects of treatment on (i) reducing viral shedding in index cases and (ii) reducing viral transmission to treatment-eligible household contacts. Four secondary outcomes were assessed including duration of viral shedding, effects on viral transmission and seroconversion, incidence of hospitalization, and incidence and severity of reported adverse events. A post-hoc at risk population was defined as households where the index case was positive at the start of the study and there was at least one treatment eligible contact in a household who tested negative for SARS-CoV-2. ResultsIn total, 1172 participants in 341 households underwent randomization, with 607 assigned to receive IFN{beta}-1 and 565 to standard care. Based on intention to treat and per protocol analyses, IFN{beta}-1 treatment was ineffective. However, in the at risk population, the relative risk of infection was reduced by 23% in treated individuals and that there was a 95% probability that IFN{beta}-1 reduced household transmission Conclusions and RelevanceRing prophylaxis with IFN{beta}-1 reduces the probability of SARS-CoV-2 transmission within a household. Trial RegistrationClinicaltrials.gov identifier: NCT04552379

Imaging Self-Healing Hydrogels and Chemotherapeutics Using CEST MRI at 3 T.

Imaging hydrogel-based local drug delivery to the brain after tumor resection has implications for refining treatments, especially for brain tumors with poor prognosis and high recurrence rate. Here, we developed a series of self-healing chitosan-dextran (CD)-based hydrogels for drug delivery to the brain. These hydrogels are injectable, self-healing, mechanically compatible, and detectable by chemical exchange saturation transfer magnetic resonance imaging (CEST MRI). CD hydrogels have an inherent CEST contrast at 1.1 ppm, which decreases as the stiffness increases. We further examined the rheological properties and CEST contrast of various chemotherapeutic-loaded CD hydrogels, including gemcitabine (Gem), doxorubicin, and procarbazine. Among these formulations, Gem presented the best compatibility with the rheological (G': 215.3 ± 4.5 Pa) and CEST properties of CD hydrogels. More importantly, the Gem-loaded CD hydrogel generated another CEST readout at 2.2 ppm (11.6 ± 0.1%) for monitoring Gem. This enabled independent and simultaneous imaging of the drug and hydrogel integrity using a clinically relevant 3 T MRI scanner. In addition, the Gem-loaded CD hydrogel exhibited a longitudinal antitumor efficacy of Gem over a week in vitro. Furthermore, the CD hydrogel could be visualized by CEST after brain injection with a contrast of 7.38 ± 2.31%. These natural labels on both the chemotherapeutics and hydrogels demonstrate unique image-guided local drug delivery for brain applications.

Effect of incident nocturnal home hemodialysis versus incident continuous ambulatory peritoneal dialysis on employment rate, clinical, and laboratory outcomes: A 1-year retrospective observation study.

INTRODUCTION: While studies demonstrated favorable outcomes of nocturnal home hemodialysis (NHHD), direct comparison on employment rate, clinical and laboratory outcomes between the NHHD and continuous ambulatory peritoneal dialysis (CAPD) had not been previously performed. METHODS: A 1-year retrospective observation study was performed in 20 incidents alternate night NHHD and 81 incident CAPD patients of Chinese ethnicity, who were sex, diabetic status, and Charlson comorbidity index matched, but not age due to our center's age limit for NHHD enrollment. The primary outcome was the difference in employment rate at 1 year. Secondary outcomes included differences in clinical parameters (weight, blood pressure, number of antihypertensive medication, dosage of phosphate binders, and erythropoietin stimulating agent) and laboratory parameters (residual renal function, mineral metabolic markers, hemoglobin). FINDINGS: NHHD subjects were 5 years younger than CAPD patients, and they had higher employment rate (80% vs. 33.3%, P < 0.01) at 1 year, with age-adjusted odds ratio for employment was 6.10 (95% confidence interval 1.77-20.99, P = 0.04). They consumed less aluminum-based phosphate binder (0 vs. 1800 mg, P < 0.01), but showed no significant disparities in other clinical parameters. Residual renal function in both groups declined comparably, nonetheless NHHD group had lower serum phosphate (1.37 vs. 1.71 mmol/L, P = 0.01) and calcium phosphate product (3.13 vs. 4.12 mmol2 /L2 , P < 0.01), with similar hemoglobin levels. DISCUSSION: NHHD appeared to offer higher employment rate, lower dosage of aluminum-based phosphate binder and mineral metabolic markers at 1 year compared with CAPD in Hong Kong.