The intraocular staining potential of anthocyanins and their retinal biocompatibility: a preclinical study

Purpose: To perform preclinical studies to determine the efficacy and safety of anthocyanins as stains for the internal limiting membrane (ILM) of the eye.

Materials and methods: Cyanidin (Cya), delphinidin (Del), luteolinidin (Lut), peonidin (Peo) and pelargonidin (Pel) were evaluated. These natural dyes were used to stain the lens capsule and ILM of pig eyes. The effects of these dyes on retinal cell viability was determined using a water-soluble tetrazolium salt assay, and oxidative stress was measured in vitro. Histopathology, in situ TUNEL labelling, transmission electronic microscopy (TEM), and electroretinography (ERG) were performed on rats following the intravitreal and subretinal injection of the neuroprotective dyes.

Results: All anthocyanins stained the lens capsule and ILM of the pigs at a concentration of 1?mg/ml. Del, Lut and Peo were non-toxic and produced survival rates in the ARPE19 and RGC5 cells that were similar to those in control cells. We treated eyes with H₂O₂ and three dyes (Del, Lut, and Peo) to explore the possible neuroprotective effects and observed significantly higher survival rates in the ARPE19 cells treated with Del, Lut or Peo and the RGC5 cells treated with Lut or Peo than those in the control cells. Three dyes were intravitreally and subretinally injected into rats in vivo, and the histology showed mildly disorganized retinal cell layers. TUNEL staining and TEM examinations did not reveal additional toxic effects. Rat ERGs were not altered after intravitreal injections.

Conclusions: This preclinical study, Del, Lut, and Peo show potential as staining agents and warrant further investigation as vital dyes.     

Iloprost use and medical management of systemic sclerosis-related vasculopathy in Italian tertiary referral centers: results from the PROSIT study

Clinical and Experimental Medicine - Vasculopathy is a crucial feature of systemic sclerosis (SSc), and Raynaud’s phenomenon (RP) and digital ulcers (DU) have a deep impact on the quality of...     

TMS of the occipital face area modulates cross-domain identity priming

Brain Structure and Function - Accumulating evidence suggests that besides its function in early facial feature processing, the role of the right occipital face area (rOFA) extends to higher level,...     

Impact of Body Mass Index on Outcomes of Hematopoietic Stem Cell Transplantation in Adults

This retrospective analysis of 2503 adult (age ≥20 years) allogeneic hematopoietic cell transplantation (HCT) recipients assessed the effect of body mass index (BMI) on transplantation outcomes. The median patient age was 51.7years. Patients with both nonmalignant and malignant diagnoses were included. Patients received either a myeloablative (52%) or a reduced-intensity (48%) conditioning regimen. Donors were either related (42%) or unrelated (58%). Cord blood recipients were excluded. Granulocyte colony-stimulating factor-mobilized peripheral blood cells were the stem cell source in 86% of transplantations. Graft-versus-host disease prophylaxis included at least 2 immunosuppressive agents, 1 of which was a calcineurin inhibitor. Patient groups were categorized as underweight, normal weight, overweight, obese, or very obese based on BMI. Endpoints included day +100 mortality, overall mortality, nonrelapse mortality (NRM), and relapse. Changes in nutritional status, based on laboratory parameters, were also examined. Underweight patients had significantly lower early and overall survival and greater NRM. Very obese patients had increased NRM, which was associated with the intensity of conditioning regimen. With long-term follow-up, increasing NRM was associated with both underweight and obese patients compared with normal-weight individuals. Changes in serum protein and albumin levels did not correlate with BMI. Although enteral nutrition is now recommended for some undernourished patients, the efficacy of enteral or parenteral nutrition has not been well studied. For obese patients, there are no guidelines regarding weight loss before transplantation, and acute weight loss in the pretransplantation period may be detrimental.     

Quality Improvement Initiative to Reduce Nighttime Noise in a Transplantation and Cellular Therapy Unit

Sleep is an essential biologic function vital for physiologic rest, healing, and emotional well-being. Sleep disruption is commonly seen in patients and caregivers with lengthy hospital stays such as patients undergoing hematopoietic stem cell transplantation and cellular therapy (TCT). Sleep disruption can lead to increased stress and fatigue, affecting caregivers’ ability to support their loved one. The global aim of our quality improvement initiative was to improve sleep quality in TCT patients and caregivers. The smart aim of our project was to decrease nighttime hallway noise from 47 dB to 43 dB and decrease the number of overnight noise peaks greater than 60 dB from 865 to 432 in 6 months. Through a cross-sectional quantitative and qualitative evaluation of sleep we had previously identified poor sleep quality, and with a cross-sectional focus group analysis of patients, caregivers, and medical staff we identified the factors associated with poor sleep. Hallway noise was a major factor. A simplified failure mode analysis identified 4 main key drivers; unobtrusive nighttime cleaning process, nighttime awareness maintenance system, quiet nighttime nursing system, and reliable nighttime awareness system. Several plan-do-study-act interventions took place and were adopted. From January to June 2018 the overnight mean decibel level decreased from 47 dB to 44 dB (6% reduction). Overnight noise spikes above 60 dB decreased from a mean of 865 spikes to a mean of 463 spikes (46% reduction). With a quality improvement initiative, we identified the causes of hallway nighttime hospital unit noise that negatively impact sleep and through a team-based approach performed interventions that successfully mitigated these factors.     

Influence of pain anticipation on brain activity and pain perception in Gulf War Veterans with chronic musculoskeletal pain

Anticipation of a painful experience can influence brain activity and increase sensitivity to experimental somatosensory stimuli in healthy adults, but this response is poorly understood among individuals with chronic musculoskeletal pain (CMP). Studies of brain and perceptual responses to somatosensory stimuli are used to make inferences about central nervous system dysfunction as a potential mechanism of symptoms. As such, we sought to (a) determine the influence of pain anticipation on pain‐relevant brain regions and pain perception, and (b) characterize potential differences in these responses between Gulf War Veterans with CMP and matched healthy control (CO) Veterans. CMP (N = 30) and CO Veterans (N = 31) were randomized to conditions designed to generate expectations that either painful (pain) or nonpainful (no pain) stimuli would be administered. Brain responses to five nonpainful thermal stimuli were measured during fMRI, and each stimulus was rated for pain intensity and unpleasantness. In the pain condition, an incremental linear decrease in activity across stimuli was observed in the posterior cingulate cortex, cingulate cortex, and middle temporal gyrus. Further, in the pain condition, differential responses were observed between CMP and CO Veterans in the middle temporal gyrus. These findings indicate that brain responses to nonpainful thermal stimuli in Veterans with CMP are sensitive to pain anticipation, and we recommend accounting for the influence of pain anticipation in future investigations of central nervous system dysfunction in CMP.