A brief fall prevention intervention for manual wheelchair users with spinal cord injuries: A pilot study

Objective: To conduct a pilot study of an intervention to decrease fall incidence and concerns about falling among individuals living with Spinal Cord Injury who use manual wheelchairs full-time.

Design: Pre/post. After a baseline assessment, a structured intervention was implemented. The assessment protocol was repeated 12 weeks after the baseline assessment.

Setting: Research laboratory and community.

Participants: 18 individuals living with SCI who use a manual wheelchair full-time with an average age of 35.78?±?13.89 years, lived with SCI for 17.06?±?14.6 years; 61.1% were female.

Intervention: A 1:1, 45 minute, in-person intervention focused on factors associated with falls and concerns about falling: transfers skills and seated postural control.

Outcome measures: Participants reported fall incidence and completed the Spinal Cord Injury Fall Concerns Scale, Community Participation Indicators and the World Health Organization Quality of Life – short version (WHOQOL-BREF). Transfer quality was assessed with the Transfer Assessment Instrument (TAI) and seated postural control with the Function In Seating Test (FIST).

Results: Recruitment, assessment and delivery of the intervention were successfully completed. After exposure to the intervention, fall incidence significantly decreased, (P?=?0.047, d_{z ?}=?0.507) and FIST scores improved (P?=?0.035, d_z? =?0.54). Significant improvements were also found in the WHOQOL-BREF Physical (P?=?0.05, d_{z ?}=?1.566) and Psychological (P?=?0.040, d_{z ?}=?0.760) domains.

Conclusion: The feasibility of the structured intervention was established and the intervention has the potential to reduce fall incidence and improve quality of life among individuals living with SCI who use a wheelchair. Appropriately powered randomized controlled trials of the program are warranted.     

Hospital admission for neurologic disorders among 5-year survivors of noncentral nervous system tumors in childhood: A cohort study within the Adult Life after Childhood Cancer in Scandinavia study

Large, comprehensive studies of the risk for neurologic disorders among long-term survivors of noncentral nervous system (CNS) childhood cancers are lacking. Thus, the aim of our study was to assess the lifetime risk of Nordic non-CNS childhood cancer survivors for neurologic disorders. We identified 15,967 5-year survivors of non-CNS childhood cancer diagnosed in Denmark, Iceland, Finland and Sweden in 1943–2008, and 151,118 matched population comparison subjects. In-patient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs). A neurologic disorder was diagnosed in 755 of the survivors while 370 were expected, yielding a RR of 2.0 (95% confidence interval (CI) 1.9–2.2). The highest risks were found among survivors of neuroblastoma (4.1; 95% CI 3.2–5.3) and leukemia (2.8; 95% CI 2.4–3.2). The AER decreased from 331 (278–383) excess neurologic disorders per 100,000 person-years 5–9 years after diagnosis to 82 (46–118) ≥ 20 years after diagnosis. Epilepsy was the most common diagnosis (n = 229, 1.4% of all survivors), and significantly increased risks were seen among survivors of eight out of 12 types of childhood cancer. Survivors of neuroblastoma had remarkably high risks (RR ≥ 10) for hospitalization for paralytic syndromes and hydrocephalus, while survivors of leukemia had additional high risks for dementia and encephalopathy. In conclusion, survivors of non-CNS childhood cancer are at high risk for neurologic disorders, especially within the first decade after diagnosis. Therefore, intensive follow-up to identify those who require close management is needed.     

Dual-Stage Picolinic Acid-Derived Inhibitors of Toxoplasma gondii

Toxoplasma gondii causes a prevalent human infection for which only the acute stage has an FDA-approved therapy. To find inhibitors of both the acute stage parasites and the persistent cyst stage that causes a chronic infection, we repurposed a compound library containing known inhibitors of parasitic hexokinase, the first step in the glycolysis pathway, along with a larger collection of new structural derivatives. The focused screen of 22 compounds showed a 77% hit rate (>50% multistage inhibition) and revealed a series of aminobenzamide-linked picolinic acids with submicromolar potency against both T. gondii parasite forms. Picolinic acid 23, designed from an antiparasitic benzamidobenzoic acid class with challenging ADME properties, showed 60-fold-enhanced solubility, a moderate LogD_7.4, and a 30% improvement in microsomal stability. Furthermore, isotopically labeled glucose tracing revealed that picolinic acid 23 does not function by hexokinase inhibition. Thus, we report a new probe scaffold to interrogate dual-stage inhibition of T. gondii.     

Influence of pitch size and age category on the physical and physiological responses of young football players during small-sided games using GPS devices

ABSTRACT

This study aimed to compare the physical and physiological responses of young football players of different categories during small-sided games (SSGs) played on different pitch sizes. Forty-eight (24 U-13 and 24 U-14) athletes played a 3 vs. 3 + 1 SSG in two experimental conditions: regular (36 × 27 m) and large pitch sizes (40 × 29 m). The total distance covered, the distances covered at different speed zones (0 to 6.9 km/h, 6.9 to 14.3, and 14.3 to 21.4), maximum heart rate, and mean heart rate were recorded. The results showed that older athletes covered larger distances during SSGs (p = 0.001; d = 0.937; large effect) and lower distances at the lowest (0–6.9 km/h) speed zone (p = 0.001; d = 0.657; moderate-to-large effect). Neither the physical nor physiological variables (except for distance covered between 14.3 and 21.4 km/h) differed between pitch sizes. This result indicates that pitch size may not impact the physical or physiological responses of U-13 and U-14 players during SSGs, but differences between categories were found. In conclusion, the development of tactical skills may be desirable to better explore the available space in the same age categories.     

Application of the adverse outcome pathway framework to genotoxic modes of action

In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc.     

Functionally navigated transcranial magnetic stimulation to evoke lingual pressure in stroke survivors with dysphagia and healthy adults: a proof of concept trial

ABSTRACT

Background

Post-stroke dysphagia is characterized by reduced corticolingual excitability and lingual pressure; however, it remains unknown if transcranial magnetic stimulation (TMS) directly facilitates lingual pressure generation.