Beneficial effects of the nutritional supplements on the development of diabetic retinopathy

Abstract Purpose Increased oxidative stress and inflammatory mediators are implicated in the development of diabetic retinopathy, and in rats, its development can be prevented by antioxidants. Carotenoids are some of the powerful antioxidants, and diabetes decreases lutein and zeaxanthin levels in the serum and retina. The aim of this study is to investigate the effect of carotenoid containing nutritional supplements (Nutr), which is in clinical trials for ‘Diabetes Vision Function’, on diabetic retinopathy. Methods Streptozotocin-induced diabetic rats (Wistar, male) were fed Purina 5001 supplemented with nutritional supplements containing zeaxanthin, lutein, lipoic acid, omega-3 fatty acids and other nutrients, or without any supplementation. Retinal function was analyzed at ~4 months of diabetes by electroretinography. After 11 months of diabetes, capillary cell apoptosis (TUNEL-staining) and histopathology (degenerative capillaries) were quantified in trypsin-digested retinal vasculature. Retina was also analyzed for mitochondrial damage (by quantifying gene expressions of mtDNA-encoded proteins of the electron transport chain), VEGF and inflammatory mediators, interleukin-1β and NF-kB. Results Diabetes impaired retinal function decreasing the amplitudes of both a- and b-waves. In the same animals, retinal capillary cell apoptosis and degenerative capillaries were increased by 3–4 fold. Gene expressions of mtDNA encoded proteins were decreased, and VEGF, interleukin-1β and NF-kB levels were elevated. Supplementation with the nutrients prevented increased capillary cell apoptosis and vascular pathology, and ameliorated these diabetes-induced retinal abnormalities. Conclusions Nutritional supplementation prevents diabetic retinopathy, and also maintains normal retinal function, mitochondrial homeostasis and inflammatory mediators. Thus, this supplementation could represent an achievable and inexpensive adjunct therapy to also inhibit retinopathy, a slow progressing disease feared most by diabetic patients

Measuring the Physiologic Properties of Oral Lesions Receiving Fractionated Photodynamic Therapy

Photodynamic therapy (PDT) can treat superficial, early‐stage disease with minimal damage to underlying tissues and without cumulative dose‐limiting toxicity. Treatment efficacy is affected by disease physiologic properties, but these properties are not routinely measured. We assessed diffuse reflectance spectroscopy (DRS) for the noninvasive, contact measurement of tissue hemoglobin oxygen saturation (StO2) and total hemoglobin concentration ([tHb]) in the premalignant or superficial microinvasive oral lesions of patients treated with 5‐aminolevulinic acid (ALA)‐PDT. Patients were enrolled on a Phase 1 study of ALA‐PDT that evaluated fluences of 50, 100, 150 or 200 J cm−2 delivered at 100 mW cm−2. To test the feasibility of incorporating DRS measurements within the illumination period, studies were performed in patients who received fractionated (two‐part) illumination that included a dark interval of 90–180 s. Using DRS, tissue oxygenation at different depths within the lesion could also be assessed. DRS could be performed concurrently with contact measurements of photosensitizer levels by fluorescence spectroscopy, but a separate noncontact fluorescence spectroscopy system provided continuous assessment of photobleaching during illumination to greater tissue depths. Results establish that the integration of DRS into PDT of early‐stage oral disease is feasible, and motivates further studies to evaluate its predictive and dosimetric value.Diffuse reflectance spectroscopy with a contact probe was employed as part of a fluorescence and reflectance spectroscopy system to measure the tissue hemoglobin oxygen saturation and hemoglobin content of lesions of premalignant or early microinvasive cancer of the oral cavity. Studies demonstrate the feasibility of incorporating these measurements into treatment with fractionated (two‐part) photodynamic therapy (PDT) using 5‐aminolevulinic acid. Patient‐specific differences in physiologic parameters were detectable at baseline and at times during and after PDT. Photobleaching of photosensitizer was measured by its fluorescence. Results establish the utility of rationally designed spectroscopy probes toward personalized dosimetry in PDT of oral disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113767/1/php12475.pd

Validation of Diffuse Correlation Spectroscopic Measurement of Cerebral Blood Flow Using Phase-Encoded Velocity Mapping Magnetic Resonance Imaging

Diffuse correlation spectroscopy (DCS) is a novel optical technique that appears to be an excellent tool for assessing cerebral blood flow in a continuous and non-invasive manner at the bedside. We present new clinical validation of the DCS methodology by demonstrating strong agreement between DCS indices of relative cerebral blood flow and indices based on phase-encoded velocity mapping magnetic resonance imaging (VENC MRI) of relative blood flow in the jugular veins and superior vena cava. Data were acquired from 46 children with single ventricle cardiac lesions during a hypercapnia intervention. Significant increases in cerebral blood flow, measured both by DCS and by VENC MRI, as well as significant increases in oxyhemoglobin concentration, and total hemoglobin concentration, were observed during hypercapnia. Comparison of blood flow changes measured by VENC MRI in the jugular veins and by DCS revealed a strong linear relationship, R = 0.88, p \u3c 0.001, slope = 0.91 ± 0.07. Similar correlations were observed between DCS and VENC MRI in the superior vena cava, R = 0.77, slope = 0.99 ± 0.12, p \u3c 0.001. The relationship between VENC MRI in the aorta and DCS, a negative control, was weakly correlated, R = 0.46, slope = 1.77 ± 0.45, p \u3c 0.001

Video-Only Cardiopulmonary Resuscitation Education for High-Risk Families Before Hospital Discharge: A Multicenter Pragmatic Trial

BACKGROUND: Cardiopulmonary resuscitation (CPR) training rates in the United States are low, highlighting the need to develop CPR educational approaches that are simpler, with broader dissemination potential. The minimum training required to ensure long-term skill retention remains poorly characterized. We compared CPR skill retention among laypersons randomized to training with video-only (VO; no manikin) with those trained with a video self-instruction kit (VSI; with manikin). We hypothesized that VO training would be noninferior to the VSI approach with respect to chest compression (CC) rate. METHODS AND RESULTS: We performed a prospective, cluster randomized trial of CPR education for family members of patients with high-risk cardiac conditions on hospital cardiac units, using a multicenter pragmatic design. Eight hospitals were randomized to offer either VO or VSI training before discharge using volunteer trainers. CPR skills were assessed 6 months post training. Mean CC rate among those trained with VO compared with those trained with VSI was assessed with a noninferiority margin set at 8 CC per min; as a secondary outcome, mean differences in CC depth were assessed. From February 2012 to May 2015, 1464 subjects were enrolled and 522 subjects completed a skills assessment. The mean CC rates were 87.7 (VO) CC per min and 89.3 (VSI) CC per min; we concluded noninferiority for VO based on a mean difference of -1.6 (90% confidence interval, -5.2 to 2.1). The mean CC depth was 40.2 mm (VO) and 45.8 mm (VSI) with a mean difference of -5.6 (95% confidence interval, -7.6 to -3.7). Results were similar after multivariate regression adjustment. CONCLUSIONS: In this large, prospective trial of CPR skill retention, VO training yielded a noninferior difference in CC rate compared with VSI training. CC depth was greater in the VSI group. These findings suggest a potential trade-off in efforts for broad dissemination of basic CPR skills; VO training might allow for greater scalability and dissemination, but with a potential reduction in CC depth. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01514656

A Small Molecule that Induces Intrinsic Pathway Apoptosis with Unparalleled Speed

Apoptosis is generally believed to be a process thatrequires several hours, in contrast to non-programmed forms of cell death that can occur in minutes. Our findings challenge the time-consuming nature of apoptosis as we describe the discovery and characterization of a small molecule, named Raptinal, which initiates intrinsic pathway caspase-dependent apoptosis within minutes in multiple cell lines. Comparison to a mechanistically diverse panel of apoptotic stimuli reveals that Raptinal-induced apoptosis proceeds with unparalleled speed. The rapid phenotype enabled identification of the criticalroles of mitochondrial voltage-dependent anion channel function, mitochondrial membrane potential/coupled respiration, and mitochondrial complex I, III, and IV function for apoptosis induction. Use of Raptinal in whole organisms demonstrates its utility for studying apoptosis invivo for a variety of applications. Overall, rapid inducers of apoptosis are powerful tools that will be used in a variety of settings to generate further insight into the apoptotic machinery. Palchaudhuri etal. describe the discovery of a small molecule called "Raptinal" that induces unusually rapid apoptotic cell death via the intrinsic pathway. Their work describes the utility of Raptinal as a tool for apoptosis induction relative to other available small molecules

Unstaged cancer in the United States: a population-based study

<p>Abstract</p> <p>Background</p> <p>The current study examines unstaged disease for 18 cancer sites in the United States according to the influence of age, sex, race, marital status, incidence, and lethality.</p> <p>Methods</p> <p>Analyses are based on 1,040,381 male and 1,011,355 female incident cancer cases diagnosed during 2000 through 2007. Data were collected by population-based cancer registries in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program.</p> <p>Results</p> <p>The level of unstaged disease was greater in more lethal cancers (e.g., liver, esophagus, and pancreas) compared with less deadly cancers (i.e., colon, urinary bladder, and female breast). Unstaged disease increased with age and is greater among non-married patients. Blacks compared with whites experienced significantly higher levels of unstaged cancers of the stomach, rectum, colon, skin (melanoma), urinary bladder, thyroid, breast, corpus, cervix, and ovaries, but lower levels of unstaged liver, lung and bronchial cancers. Males compared with females experienced significantly lower levels of unstaged cancers of the liver, pancreas, esophagus, and stomach, but significantly higher levels of unstaged lung and bronchial cancer and thyroid cancer. The percent of unstaged cancer significantly decreased over the study period for 15 of the 18 cancer sites.</p> <p>Conclusion</p> <p>Tumor staging directly affects treatment options and survival, so it is recommended that further research focus on why a decrease in unstaged disease did not occur for all of the cancer sites considered from 2000 to 2007, and why there are differential levels of staging between whites and blacks, males and females for several of the cancer sites.</p

Factors Associated with Response to Acetylcholinesterase Inhibition in Dementia:A Cohort Study from a Secondary Mental Health Care Case Register in London

Background: Acetylcholinesterase inhibitors (AChEIs) are widely used to delay cognitive decline in Alzheimer's disease. Observational studies in routine clinical practice have shown cognitive improvement in some groups of patients receiving these agents but longitudinal trajectories before and after AChEI initiation have not previously been considered.  Objectives: To compare trajectories of cognitive function before and after AChEI initiation and investigate predictors of these differences.  Method: A retrospective longitudinal study was constructed using data from 2460 patients who received AChEIs and who had routine data on cognitive function (Mini-Mental State Examination; MMSE) before and after AChEI initiation. Longitudinal MMSE change was modelled using three-piece linear mixed models with the following segments: 0-12 months prior to AChEI initiation, 0-6 months and 6-36 months after initiation.  Results: MMSE decline was reversed (in that the slope was improved by an average 4.2 units per year, 95% CI 3.5-4.8) during the 6-month period following AChEI initiation compared with the slope in the one year period before AChEI initiation. The slope in the period from 6-36 months following AChEI initiation returned to the pre-initiation downward trajectory. The differences in slopes in the 1 year period prior to AChEI initiation and in the 6 months after initiation were smaller among those with higher MMSE scores at the time of AChEI initiation, among those who received a vascular dementia diagnosis at any point, and among those receiving antipsychotic agents.  Conclusion: In this naturalistic observational study, changes in cognitive trajectories around AChEI initiation were similar to those reported in randomised controlled trials. The magnitude of the difference in slopes between the 1 year period prior to AChEI initiation and the 6 month period after AChEI initiation was related to level of cognitive function at treatment initiation, vascular comorbidity and antipsychotic use