Search

Abstract Objective To raise awareness of the role of environmental biofilm in the emergence and spread of antibiotic resistance and its consideration in antimicrobial stewardship. Background Antibiotic resistance is a major threat to public health. Overuse of antibiotics, increased international travel, and genetic promiscuity amongst bacteria have contributed to antibiotic resistance, and global containment efforts have so far met with limited success. Antibiotic resistance is a natural mechanism by which bacteria have adapted to environmental threats over billions of years and is caused either by genetic mutations or by horizontal gene transfer. Another ancient survival strategy involves bacteria existing within a self-produced polymeric matrix, which today is termed biofilm. Biofilm similarly enables bacterial tolerance to environmental threats, and also encourages the transfer of antibiotic resistance genes between bacterial species. This natural and ubiquitous mode of bacterial life has not been considered amongst strategies to tackle antibiotic resistance in healthcare facilities, despite its ability to significantly enhance bacterial survival and persistence, and to encourage antibiotic resistance. Conclusion Biofilm must be considered synonymously with antibiotic resistance because of its proficiency in transferring resistance genes as well as its innate phenotypic tolerance to antibiotics. Although biofilm falls outside of the current definition of antimicrobial stewardship, greater awareness of the existence, ubiquity, and consequences of environmental biofilm amongst healthcare practitioners is crucial to improving hygiene practices and controlling the emergence and spread of antibiotic resistance in healthcare facilities.

Currently, no treatments available for Parkinson’s disease (PD) can slow PD progression. At the early stage of the disease, only a subset of individuals with PD progress quickly, while the majority have a slowly progressive form of the disease. In developing treatments that aim to slow PD progression, clinical trials aim to include individuals who are likely to progress faster, such that a treatment effect, if one exists, can be identified easier and earlier. The aim of the present study was to identify baseline predictors of clinical progression in early PD. We analyzed 12-month data acquired from the PASADENA trial Part 1 (NCT03100149, n = 76 participants who were allocated to the placebo arm and did not start symptomatic therapy) and the Parkinson’s Progression Markers Initiative (PPMI) study (n = 139 demographically and clinically matched participants). By using ridge regression models including clinical characteristics, imaging, and non-imaging biomarkers, we found that Hoehn and Yahr stage and dopamine transporter single-photon emission computed tomography specific binding ratios (Dat-SPECT SBR) in putamen ipsilateral to the side of motor symptom onset predicted PD progression at the early stage of the disease. Further studies are needed to confirm the validity of these predictors to identify with high accuracy individuals with early PD with a faster progression phenotype.

Background: Currently available treatments for Parkinson's disease (PD) do not slow clinical progression nor target alpha-synuclein, a key protein associated with the disease.Objective: The study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD.Methods: The PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study. Individuals with early PD, recruited across the US and Europe, received monthly intravenous doses of prasinezumab (1,500 or 4,500 mg) or placebo for a 52-week period (Part 1), followed by a 52-week extension (Part 2) in which all participants received active treatment. Key inclusion criteria were: aged 40–80 years; Hoehn & Yahr (H&Y) Stage I or II; time from diagnosis ≤2 years; having bradykinesia plus one other cardinal sign of PD (e.g., resting tremor, rigidity); DAT-SPECT imaging consistent with PD; and either treatment naïve or on a stable monoamine oxidase B (MAO-B) inhibitor dose. Study design assumptions for sample size and study duration were built using a patient cohort from the Parkinson's Progression Marker Initiative (PPMI). In this report, baseline characteristics are compared between the treatment-naïve and MAO-B inhibitor-treated PASADENA cohorts and between the PASADENA and PPMI populations.Results: Of the 443 patients screened, 316 were enrolled into the PASADENA study between June 2017 and November 2018, with an average age of 59.9 years and 67.4% being male. Mean time from diagnosis at baseline was 10.11 months, with 75.3% in H&Y Stage II. Baseline motor and non-motor symptoms (assessed using Movement Disorder Society—Unified Parkinson's Disease Rating Scale [MDS-UPDRS]) were similar in severity between the MAO-B inhibitor-treated and treatment-naïve PASADENA cohorts (MDS-UPDRS sum of Parts I + II + III [standard deviation (SD)]; 30.21 [11.96], 32.10 [13.20], respectively). The overall PASADENA population (63.6% treatment naïve and 36.4% on MAO-B inhibitor) showed a similar severity in MDS-UPDRS scores (e.g., MDS-UPDRS sum of Parts I + II + III [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naïve).Conclusions: The PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD.Trial Registration: NCT03100149.

IntroductionThere has been limited study of patient-reported outcomes (PROs) in patients at risk of limb loss. Our primary objective was to estimate the prevalence of disability in this patient population using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0).Materials and methodsWe recruited patients referred to a limb-preservation clinic. Patients self-reported their disability status using the 12-domain WHODAS 2.0. Severity of disability in each domain was scored from 1 = none to 5 = extreme and the total normalized to a 100-point scale (total score ≥25 = clinically significant disability). We also asked patients about wound-specific concerns and wound-related discomfort or distress.ResultsWe included 162 patients. Reasons for clinic referral included arterial-insufficient (37.4%), postoperative (25.9%), and mixed etiology (10.8%) wounds. The mean WHODAS 2.0 disability score was 35.0 (standard deviation = 16.0). One-hundred-and-nineteen (73.5%) patients had clinically significant disability. Patients reported they had the greatest difficulty walking a long distance (mean score = 4.2), standing for long periods of time (mean score = 3.6), taking care of household responsibilities (mean score = 2.7), and dealing with the emotional impact of their health problems (mean score = 2.5). In the two-weeks prior to presentation, 87 (52.7%) patients expressed concern over their wound(s) and 90 (55.6%) suffered a moderate amount or great deal of wound-related discomfort or distress. In adjusted ordinary least squares regression models, although WHODAS 2.0 disability scores varied with changes in wound volume (p = 0.03) and total revised photographic wound assessment tool scores (pDiscussionThe majority of people at risk of limb loss report suffering a substantial burden of disability, pain, and wound-specific concerns. Research is needed to further evaluate the WHODAS 2.0 in a multicenter fashion among these patients and determine whether care and interventions may improve their PROs.

When C.S. Lewis read E. M. W. Tillyard’s book Milton (1930), he engaged with the text through markings and annotations, particularly in the inside cover of the book. In this book, Lewis wrote an extended paragraph in direct response to Tillyard’s claim that it is necessary to understand the state of mind of a poet in order to analyze his or her work. Lewis’ notes focus on John Milton’s epic poem Paradise Lost (1667) and bear immense similarity to the themes found in his work A Preface to Paradise Lost (1942). When Lewis and Tillyard debated various aspects of poetry in the 1930s, their articles were collected and published together as The Personal Heresy (1939). Due to the notes found in Lewis’ personal copy of Milton, the claims made in the articles, and the striking similarities seen in Preface, Tillyard’s impact on Lewis cannot be ignored and he must be viewed as a direct influence for Lewis’ Preface.

We established a collection of 7,000 transgenic lines of Drosophila melanogaster. Expression of GAL4 in each line is controlled by a different, defined fragment of genomic DNA that serves as a transcriptional enhancer. We used confocal microscopy of dissected nervous systems to determine the expression patterns driven by each fragment in the adult brain and ventral nerve cord. We present image data on 6,650 lines. Using both manual and machine-assisted annotation, we describe the expression patterns in the most useful lines. We illustrate the utility of these data for identifying novel neuronal cell types, revealing brain asymmetry, and describing the nature and extent of neuronal shape stereotypy. The GAL4 lines allow expression of exogenous genes in distinct, small subsets of the adult nervous system. The set of DNA fragments, each driving a documented expression pattern, will facilitate the generation of additional constructs for manipulating neuronal function.

Objectives: Acute vocal fold edema (VFE) is often a consequence of illness, allergy, or voice overuse, causing dysphonia. Although VFE typically resolves with voice rest and treatment of predisposing causes, oral glucocorticoids are often considered for performers with imminent performance demands. There are limited data about performers’ perceptions of vocal change during treatment and how this relates to their ability to perform. This study aims to examine performers’ self-perceptions of vocal function with steroid treatment. Methods: Fifty-five performers (34 F; 21 M) diagnosed with VFE who chose treatment with a 6-day methylprednisolone taper were prospectively assessed. They completed the Evaluation of the Ability to Sing Easily (EASE) and reported on their voice use, regimen, performance obligations, and ability to perform. Findings were compared between Day 1 and Day 6 using paired t-tests and nonparametric Wilcoxon signed-rank tests. Results: Nearly all subjects completed scheduled performances without interruption. Following treatment, all subscales of the EASE were decreased at Day 6 (Vocal Function 29.78–20.59; Pathologic Risk Indicator 26.60–17.33; Vocal Concerns 6.10–4.20). These differences were statistically significant (p < 0.0001) and greater in subjects with performances scheduled and subjects who consistently completed vocal warmups. These findings demonstrate significant improvement in several facets of performers’ self-perception of function. Conclusion: Subjects reported significant improvement in vocal function with oral steroid treatment and were able to meet performance obligations. It remains important that steroids are not prescribed without laryngeal examination. Examination should be repeated when dysphonia persists, recurs swiftly, or when patients seek repeated treatment, as there may be increased risk of adverse outcomes, and continued steroid use may mask underlying chronic pathology that is best treated by other means. [ABSTRACT FROM AUTHOR]

Two experiments examined the relation between revision and task definition among college students in writing courses. In Experiment 1, students prompted to make global revisions to their drafts of college application letters improved their drafts more than students not prompted to make global revisions. Results of Experiment 1 extended results of D. L. Wallace and J. R. Hayes (1991), who found the same effect for students revising text they had not written. In Experiment 2, the treatment did not improve revisions by college students (identified as measured by low SAT verbal scores) who completed the same writing task. Together, results of these 2 experiments suggest that the prompt to revise globally may be effective in helping entry-level college writing students improve their texts (the prompt seems to have encouraged them to make better revisions) but that it is not effective in helping basic-level college writing students revise.