Effects of a Laxation and Probiotic Bowel Preparation Regimen: A Randomized Controlled Trial in Patients Undergoing Prostate Radiation Therapy.

Aim: To determine the effect of bulking and osmotic laxation regimens on reducing rectal gas in patients receiving external beam radiation therapy for prostate cancer.Methods: A single blinded randomized controlled trial was conducted. Participants assigned to the intervention group (IG) were instructed to consume a bulking laxative and probiotic and the standard care group (SC) instructed to consume an osmotic laxative. Both groups followed a standard low gas diet. Rectal gas ratings were determined from cone-beam computed tomography (CBCT) scans. Dietary and laxative compliance, bowel habits, fiber and fluid intakes were determined from food diaries.Results: Demographic characteristics were not significantly different between the two treatment arms. The mean age was 74 years. Participants were randomized into the IG (n = 8) and SC group (n = 9). Analysis of 433 CBCT scans indicate the odds of a higher rectal gas rating were significantly increased for the IG compared with the SC group (OR 3.2, 95% CI 1.77-5.78, P < 0.001).Conclusions: The osmotic laxative was more effective at achieving lower rectal gas levels than a bulking laxative with probiotic in this study. Larger studies of commonly used laxatives are required to develop recommendations for bowel preparation during radiotherapy to the prostate.

The Potential of Stem Cells in Treatment of Traumatic Brain Injury.

PURPOSE OF REVIEW: Traumatic brain injury (TBI) is a global public health concern, with limited treatment options available. Despite improving survival rate after TBI, treatment is lacking for brain functional recovery and structural repair in clinic. Recent studies have suggested that the mature brain harbors neural stem cells which have regenerative capacity following brain insults. Much progress has been made in preclinical TBI model studies in understanding the behaviors, functions, and regulatory mechanisms of neural stem cells in the injured brain. Different strategies targeting these cell population have been assessed in TBI models. In parallel, cell transplantation strategy using a wide range of stem cells has been explored for TBI treatment in pre-clinical studies and some in clinical trials. This review summarized strategies which have been explored to enhance endogenous neural stem cell-mediated regeneration and recent development in cell transplantation studies for post-TBI brain repair. RECENT FINDINGS: Thus far, neural regeneration through neural stem cells either by modulating endogenous neural stem cells or by stem cell transplantation has attracted much attention. It is highly speculated that targeting neural stem cells could be a potential strategy to repair and regenerate the injured brain. Neuroprotection and neuroregeneration are major aspects for TBI therapeutic development. With technique advancement, it is hoped that stem cell-based therapy targeting neuroregeneration will be able to translate to clinic in not so far future.

Reasons persons with COPD do not walk and relationship with daily step count.

BACKGROUND: Physical activity (PA) is significantly reduced in persons with COPD. Assessing reasons why persons with COPD do not engage in PA can guide development of effective interventions to promote PA. METHODS: We queried 102 participants with stable COPD about disease-related and general reasons why they do not walk more. The StepWatch Activity Monitor (Orthocare Innovations, Mountlake Terrace, WA, USA) assessed daily step count, a direct measure of PA. Regression models assessed daily step count by response categories, adjusting for age and FEV1 % predicted. RESULTS: Subjects had mean age 72 ± 8 years and mean FEV1 1.48 ± 0.55 L (52 ± 19% predicted). COPD-related worries of becoming short of breath (SOB), needing to use inhalers, or oxygen level becoming low were endorsed by 31, 14, and 12 subjects, respectively. Controlling for age and FEV1% predicted, those who worried about becoming SOB walked an average of 1,329 fewer steps per day than those who did not worry (p = 0.020). Those who worried about needing to use inhalers walked an average of 1,806 fewer steps per day than those who did not worry (p = 0.016). Subjects who were the most motivated and confident walked significantly more than those who were the least motivated and confident. CONCLUSIONS: Presence of COPD-related reasons and lower motivation and confidence are associated with lower daily step count. Management of dyspnea and education about medication use during exercise, and strategies to increase motivation and confidence could facilitate walking in COPD.

Enhanced responses to somatostatin interneuron activation in developmentally malformed cortex.

Intractable epilepsy is commonly associated with developmental cortical malformations. Using the rodent freeze lesion model, we have sought the underlying circuit abnormalities contributing to the epileptiform activity that occurs in association with the structural pathology of four-layered microgyria. We showed previously that within the epileptogenic paramicrogyral region (PMR) surrounding the malformation, non-fast-spiking neurons commonly containing somatostatin (SSt) exhibit alterations, including having a greater maximum firing rate. Here we examined the output of SSt interneurons with optogenetics, using SSt-Cre mice mated to mice with floxed channelrhodopsin-2. Voltage clamp recordings from layer V pyramidal neurons in ex vivo slices had significantly enhanced SSt-evoked inhibitory postsynaptic currents in PMR cortex compared to control. In addition, under conditions of low-Mg2+ artificial cerebral spinal fluid (aCSF), light activation of the SSt neurons evoked field potential epileptiform activity in the PMR cortex, but not in control. These data suggest that within the PMR cortex, SSts have a significantly larger effect on excitatory neurons. Surprisingly, the network effect of this enhanced inhibition is hyperexcitability with propagating epileptiform activity, perhaps due to disinhibition of other interneuron cell types or to enhanced synchrony of excitatory cortical elements. This identification creates a new locus for potential modulation of epileptiform activity associated with cortical malformation.

Daily step count is associated with plasma C-reactive protein and IL-6 in a US cohort with COPD.

BACKGROUND: Physical activity is an important clinical marker of disease status in COPD. COPD is also characterized by low-grade systemic inflammation. However, the relationship between physical activity and systemic inflammation in COPD is unclear. METHODS: We monitored daily step count, a directly measured physical activity, using the StepWatch Activity Monitor, an ankle-worn accelerometer, in 171 people with stable COPD. Exercise capacity was assessed with the 6-min walk test (6MWT). We measured plasma C-reactive protein (CRP) and IL-6 levels. Linear regression models examined the cross-sectional associations of daily step count and 6MWT distance with CRP and IL-6 levels. RESULTS: Subjects had a mean age 72±8 years and mean FEV1 1.5±0.57 L (54±20% predicted). Median daily step count was 5,203 (interquartile range [IQR], 3,627-7,024], CRP level was 2.4 mg/L (IQR, 1.2-5.0), and IL-6 level was 2.9 pg/mL (IQR, 2.0-5.1). Each 1,000-step increase in daily step count was associated with a 0.94 mg/L and 0.96 pg/mL decrease in CRP (P=.020) and IL-6 (P=.044) levels, respectively, adjusting for age, FEV1 % predicted, pack-years smoked, cardiac disease, current statin use, history of acute exacerbations, and season. There was a significant linear trend of increasing daily step count by quartiles and decreasing CRP (P=.0007) and IL-6 (P=.023) levels. Higher 6MWT distance was also significantly associated with lower CRP and IL-6 values. CONCLUSION: People with COPD who walked the most had the lowest plasma CRP and IL-6 levels. These results provide the conceptual basis to study whether an intervention to promote walking will reduce systemic inflammation in people with COPD.

Daily step count predicts acute exacerbations in a US cohort with COPD.

BACKGROUND: COPD is characterized by variability in exercise capacity and physical activity (PA), and acute exacerbations (AEs). Little is known about the relationship between daily step count, a direct measure of PA, and the risk of AEs, including hospitalizations. METHODS: In an observational cohort study of 169 persons with COPD, we directly assessed PA with the StepWatch Activity Monitor, an ankle-worn accelerometer that measures daily step count. We also assessed exercise capacity with the 6-minute walk test (6MWT) and patient-reported PA with the St. George's Respiratory Questionnaire Activity Score (SGRQ-AS). AEs and COPD-related hospitalizations were assessed and validated prospectively over a median of 16 months. RESULTS: Mean daily step count was 5804±3141 steps. Over 209 person-years of observation, there were 263 AEs (incidence rate 1.3±1.6 per person-year) and 116 COPD-related hospitalizations (incidence rate 0.56±1.09 per person-year). Adjusting for FEV1 % predicted and prednisone use for AE in previous year, for each 1000 fewer steps per day walked at baseline, there was an increased rate of AEs (rate ratio 1.07; 95%CI = 1.003-1.15) and COPD-related hospitalizations (rate ratio 1.24; 95%CI = 1.08-1.42). There was a significant linear trend of decreasing daily step count by quartiles and increasing rate ratios for AEs (P = 0.008) and COPD-related hospitalizations (P = 0.003). Each 30-meter decrease in 6MWT distance was associated with an increased rate ratio of 1.07 (95%CI = 1.01-1.14) for AEs and 1.18 (95%CI = 1.07-1.30) for COPD-related hospitalizations. Worsening of SGRQ-AS by 4 points was associated with an increased rate ratio of 1.05 (95%CI = 1.01-1.09) for AEs and 1.10 (95%CI = 1.02-1.17) for COPD-related hospitalizations. CONCLUSIONS: Lower daily step count, lower 6MWT distance, and worse SGRQ-AS predict future AEs and COPD-related hospitalizations, independent of pulmonary function and previous AE history. These results support the importance of assessing PA in patients with COPD, and provide the rationale to promote PA as part of exacerbation-prevention strategies.

Daily step counts in a US cohort with COPD.

BACKGROUND: Baseline values for daily step counts in US adults with COPD and knowledge of its accurate measurement, natural change over time, and independent relationships with measures of COPD severity are limited. METHODS: 127 persons with stable COPD wore the StepWatch Activity Monitor (SAM) for 14 days, and 102 of them wore it a median 3.9 months later. SAM counts were compared to manual counts in the clinic. We assessed change over time, the effect of season, and relationships with forced expiratory volume in 1 s (FEV(1)) % predicted, 6-min walk test (6MWT) distance, the modified Medical Research Council (MMRC) dyspnea score, and the St. George's Respiratory Questionnaire Total Score (SGRQ-TS). RESULTS: 98% of subjects were males, with mean age 71 ± 8 years and FEV(1) 1.48 ± 0.54 L (52 ± 19% predicted). All 4 GOLD stages were represented, with the most subjects in GOLD II (44%) and GOLD III (37%). The SAM had >90% accuracy in 99% of subjects. Average step count was 5680 steps/day, which decreased with increasing GOLD stage (p = 0.0046). Subjects walked 645 fewer steps/day at follow-up, which was partly explained by season of monitoring (p = 0.013). In a multivariate model, FEV(1) % predicted, 6MWT distance and MMRC score were weakly associated with daily step counts, while SGRQ-TS was not. CONCLUSIONS: These findings will aid the design of future studies using daily step counts in COPD. Accurately measured, daily step counts decline over time partly due to season and capture unique information about COPD status.

A pilot study of an Internet walking program and pedometer in COPD.

BACKGROUND: Higher levels of physical activity are associated with better functional status, fewer hospital admissions, and lower mortality. In this pilot study, we examined the feasibility and safety of a novel program that combines a pedometer with a website to increase walking. METHODS: 27 persons with stable COPD wore the Omron HJ-720ITC pedometer and used the website for 90 days. They uploaded step-count data to the study server using their home computer and received an email each week with their individualized step-count goal. The website provided step-count feedback, education, and motivational content. Subjects participated in a monthly semi-structured interview by telephone. Subjects reported changes in medical condition by telephone or on the website. Paired T-tests assessed change in daily step counts. RESULTS: Subjects were males, mean age 72 ± 8 years, with moderate COPD, FEV(1) 1.57 ± 0.48 L (55 ± 16% predicted). 87% and 65% reported no problems using the pedometer and website, respectively. At month 3, 96% reported it was true that they knew their step count goal every day, and 52% reported that they were able to reach their goal. 95% of participants said they would recommend the walking program to another person with COPD. Eight subjects experienced breathing problems unrelated to the intervention. In 24 subjects with step counts at baseline and month 3, there was a significant increase of 1263 steps per day (approximately 1.0 km), p = 0.0054. CONCLUSIONS: The use of a website and pedometer was feasible and safe, and persons increased their daily walking.

Cancer type-specific tNOX isoforms: A putative family of redox protein splice variants with cancer diagnostic and prognostic potential.

A proteomics approach with detection on western blots using an S-peptide tagged pan-tNOX (ENOX2) recombinant (scFv) antibody followed by alkaline phosphatase-linked anti S has revealed a family of more than 20 ENOX2 isoforms of varying molecular weights (34 to 94 kDa) and mostly of low isoelectric points (4.6 +/- 0.7) based on serum analysis. Different isoforms characterize cancers of different tissue origins indicative of both cancer presence and tissue site of origin. ENOX2 proteins are cancer-associated and differ from constitutive (CNOX or ENOX1) proteins primarily by the absence of a drug binding site to which the cancer-specific scFv is directed. All are located on the cell surface where they function both as terminal oxidases for plasma membrane electron transport and carry out protein disulfide-thiol interchange. These proteins are shed into the blood and can also be found in urine. The tNOX isoform technology is under development as a clinical aid to identify unknown or uncertain primary cancers, evaluation of metastatic spread in post surgery patients, monitoring remission following cessation of therapy and for early diagnosis in at-risk populations.

Age-related ENOX protein (arNOX) activity correlated with oxidative skin damage in the elderly.

ENOX proteins with an oscillatory pattern of production of superoxide (measured by ferricytochrome c reduction) and with a period length of 26 min increase linearity with age beginning at about 30 y to a maximum of about age 60. The proteins are shed and appear in serum, saliva and urine. Enhanced arNOX activity correlates with age and with oxidative changes contributing to skin aging. Topical cosmetic preparations containing substances that block arNOX activity are under evaluation to reduce visible symptoms of skin aging.