A Canadian Working Group report on fecal microbial therapy: microbial ecosystems therapeutics

A working group from across Canada comprised of clinician and basic scientists, epidemiologists, ethicists, Health Canada regulatory authorities and representatives of major funding agencies (Canadian Institutes of Health Research and the Crohn's and Colitis Foundation of Canada) met to review the current experience with fecal microbial therapy and to identify the key areas of study required to move this field forward. The report highlights the promise of fecal microbial therapy and related synthetic stool therapy (together called 'microbial ecosystems therapeutics') for the treatment of Clostridium difficile colitis and, possibly, other disorders. It identifies pressing clinical issues that need to be addressed as well as social, ethical and regulatory barriers to the use of these important therapies.     

Topographic Distribution and Progression of Soft Drusen Volume in Age-Related Macular Degeneration Implicate Neurobiology of Fovea

PurposeTo refine estimates of macular soft drusen abundance in eyes with age-related macular degeneration (AMD) and evaluate hypotheses about drusen biogenesis, we investigated topographic distribution and growth rates of drusen by optical coherence tomography (OCT). We compared results to retinal features with similar topographies (cone density and macular pigment) in healthy eyes.MethodsIn a prospective study, distribution and growth rates of soft drusen in eyes with AMD were identified by human observers in OCT volumes and analyzed with computer-assistance. Published histologic data for macular cone densities (n = 12 eyes) and in vivo macular pigment optical density (MPOD) measurements in older adults with unremarkable maculae (n = 31; 62 paired eyes, averaged) were revisited. All values were normalized to Early Treatment Diabetic Retinopathy Study (ETDRS) subfield areas.ResultsSixty-two eyes of 44 patients were imaged for periods up to 78 months. Soft drusen volume per unit volume at baseline is 24.6-fold and 2.3-fold higher in the central ETDRS subfield than in outer and inner rings, respectively, and grows most prominently there. Corresponding ratios (central versus inner and central versus outer) for cone density in donor eyes is 13.3-fold and 5.1-fold and for MPOD, 24.6 and 23.9-fold, and 3.6 and 3.6-fold.ConclusionsNormalized soft drusen volume in AMD eyes as assessed by OCT is ≥ 20-fold higher in central ETDRS subfields than in outer rings, paralleling MPOD distribution in healthy eyes. Data on drusen volume support this metric for AMD risk assessment and clinical trial outcome measure. Alignment of different data modalities support the ETDRS grid for standardizing retinal topography in mechanistic studies of drusen biogenesis.     

Tantalum(v) 1,3-propanediolate β-diketonate solution as a precursor to sol–gel derived,metal oxide thin films

Tantalum oxide is ubiquitous in everyday life, from capacitors in electronics to ion conductors for electrochromic windows and electrochemical storage devices. Investigations into sol–gel deposition of tantalum oxide, and its sister niobium oxide, has accelerated since the 1980s and continues to this day. The aim of this study is to synthesize a near UV sensitive, air stable, and low toxicity tantalum sol–gel precursor solution for metal oxide thin films – these attributes promise to reduce manufacturing costs and allow for facile mass production. By utilizing 1D and 2D nuclear magnetic resonance, this study shows that by removing ethanol from the precursor solution at a relatively low temperature and pressure, decomposition of the photosensitive complex can be minimized while obtaining a precursor solution with sufficient stability for storage and processing in the atmosphere. The solution described herein is further modified for inkjet printing, where multiple material characterization techniques demonstrate that the solution can be utilized in low temperature, photochemical solution deposition of tantalum oxide, which is likely amorphous. Tested substrates include amorphous silica, crystalline silicon wafer, and gold/titanium/PET foil. The hope is that these results may spark future investigations into electronic, optical, and biomedical device fabrication with tantalum oxide, and potentially niobium oxide, based films using the proposed synthesis method.

Synthesis of tantalum(v) 1,3-propanediolate β-diketonate solution and use in photochemical solution deposition to form tantalum oxide films.     

The influence of clinical course after lung transplantation on rehabilitation success

Pulmonary rehabilitation (PR) is a cornerstone of treatment following lung transplantation (LTx). The aim of this study was to observe the influence of a prolonged postsurgical clinical course on success of a 3‐week inpatient PR. LTx recipients were divided according to their clinical course defined by their individual length of stay (LOS) in the transplant center (cohort 1: LOS >; cohort 2: ≤42 days). Peak work rate (PWR), maximum oxygen uptake (VO_2max), 6‐min walk distance (6‐MWD), vital capacity (VC), forced expiratory volume in one second (FEV1), physical activity of daily life (ADL), and health‐related quality of life (HRQoL) measured using Short Form 36 questionnaire (SF36) were assessed at beginning and completion of PR. A total of 138 patients were included (LOS >42 days: 30; LOS ≤42 days: 108). At completion, physical functioning (VC, FEV1, PWR, VO_2max, 6‐MWD, ADL), and HRQoL (all SF36 domains) improved in each cohort (P < 0.05). No differences were found in between both cohorts in VC, FEV1, and ADL (n.s.), but in PWR, 6‐MWD, and the SF36 domain ‘physical functioning’ (P < 0.05). A 3‐week inpatient PR improves physical functioning despite prolonged hospitalization. HRQoL is close to normal. (ClinicalTrials.gov. identifier: NCT00759538)     

Randomized placebo‐controlled human pilot study of cold atmospheric argon plasma on skin graft donor sites

Cold atmospheric plasma has already been shown to decrease the bacterial load in chronic wounds. However, until now it is not yet known if plasma treatment can also improve wound healing. We aimed to assess the impact of cold atmospheric argon plasma on the process of donor site healing. Forty patients with skin graft donor sites on the upper leg were enrolled in our study. The wound sites were divided into two equally sized areas that were randomly assigned to receive either plasma treatment or placebo (argon gas) for 2 minutes. Donor site healing was evaluated independently by two blinded dermatologists, who compared the wound areas with regard to reepithelialization, blood crusts, fibrin layers, and wound surroundings. From the second treatment day onwards, donor site wound areas treated with plasma (n = 34) showed significantly improved healing compared with placebo‐treated areas (day 1, p = 0.25; day 2, p = 0.011; day 3, p < 0.001; day 4, p < 0.001; day 5, p = 0.004; day 6, p = 0.008; day 7, p = 0.031). Positive effects were observed in terms of improved reepithelialization and fewer fibrin layers and blood crusts, whereas wound surroundings were always normal, independent of the type of treatment. Wound infection did not occur in any of the patients, and no relevant side effects were observed. Both types of treatment were well tolerated. The mechanisms contributing to these clinically observed effects should be further investigated.     

P300 in obsessive–compulsive disorder: Source localization and the effects of treatment

Converging evidence suggests that frontostriatal abnormalities underlie OCD symptoms. The event-related potential P300 is generated along a widely distributed network involving several of the areas implicated in OCD. P300 abnormalities reported in patients with OCD suggest increased activity in these areas. The aim of the present study was to investigate this assumption in unmedicated patients with OCD, and to assess the effects of OCD treatment on P300 brain activity patterns. Seventy-one unmedicated patients with a DSM-IV diagnosis of OCD and 71 age- and gender-matched healthy control subjects participated in the study. The P300 was obtained through 32-channel EEG during an auditory oddball paradigm. Forty-three patients underwent a second EEG assessment after treatment with sertraline and behavioural therapy. Low-resolution electromagnetic tomography (LORETA) was used to localize the sources of brain electrical activity. Results: Increased P300-related activity was observed predominantly in the left orbitofrontal cortex, but also in left prefrontal, parietal and temporal areas, in patients compared to controls at baseline. After treatment, reduction of left middle frontal cortex hyperactivity was observed in patients. Conclusions: Findings of increased activity in frontoparietal areas in patients are consistent with several previous studies. Importantly, OCD treatment led to reduction of hyperactivity in the left middle frontal cortex, an area associated with context processing and uncertainty that might be important for the emergence of OCD symptoms. Thus, the present study is the first to show an association between P300 abnormalities and activity in brain regions postulated to be involved in the pathophysiology of OCD.