Is treadmill walking with virtual reality an acceptable and plausible training modality for stroke survivors?

Introduction and Objectives: For many stroke survivors recovering independent walking is an important objective, however, although most survivors recover some walking ability it is often insufficient to meet the challenges of community walking[1]. Treadmill walking, through forced use of the paretic side, has some evidence as an intervention but lacks transfer to community walking[2]. With the rationale of providing a more realistic, variable walking experience, the addition of virtual reality (VR) to treadmills is a recent, promising, development. This aim of this study, therefore, was to investigate the credibility and acceptability of treadmill training with VR among stroke survivors. Methods: This was a feasibility study testing the validity of treadmill training with and without VR through comparison with overground walking. User acceptability was assessed through independent interviews. Six ambulant stroke survivors (aged 56.5±10.6years, 116±93.3months post stroke) were recruited from local stroke clubs. They attended an introductory session for baseline measurements (over ground gait biomechanics, functional mobility and cognition) and familiarisation with the treadmill VR system (MOTEKMedical, Netherlands) including wearing a harness. They then participated in two training sessions, one week apart, each session included treadmill walking without VR (TW) and treadmill walking with VR (TWVR) e.g. road and forest paths visualisations. The final session included a second measurement of gait biomechanics which provided the data for statistical comparison. Each individual was independently interviewed before and after their participation. Results: In general minor, non-significant, differences were observed for TM, TMVR and overground walking. There was, however, a consistent, and statistically significant (p= 0.032) finding of greater hip flexion for TWVR, see table for details. Universally, participants found the experience acceptable and enjoyable, although “challenging”. Conclusion: This feasibility study found treadmill walking (with and without VR) to be similar enough to overground walking to justify it as a training modality for chronic stroke survivors who had already attained some independence in walking. One possible difference, greater hip flexion during treadmill walking, may be a product of harness wearing, and/or relate to the setup of the visualisations. Participants found the experience of treadmill walking acceptable. Although they preferred walking with the visualisations there were few biomechanical differences to simple treadmill walking. Further exploration of individual variability, however, should be undertaken as this may be a factor in ranslating gains from treadmill training to community walking. In conclusion, similarities between overground and treadmill walking (with and without VR) support its use as a training modality in stroke rehabilitation. No great advantage was evident from the use of visualisation other than participant’s preference, however these findings require further testing

Unusual structures are present in DNA fragments containing super-long Huntingtin CAG repeats.

BACKGROUND: In the R6/2 mouse model of Huntington's disease (HD), expansion of the CAG trinucleotide repeat length beyond about 300 repeats induces a novel phenotype associated with a reduction in transcription of the transgene. METHODOLOGY/PRINCIPAL FINDINGS: We analysed the structure of polymerase chain reaction (PCR)-generated DNA containing up to 585 CAG repeats using atomic force microscopy (AFM). As the number of CAG repeats increased, an increasing proportion of the DNA molecules exhibited unusual structural features, including convolutions and multiple protrusions. At least some of these features are hairpin loops, as judged by cross-sectional analysis and sensitivity to cleavage by mung bean nuclease. Single-molecule force measurements showed that the convoluted DNA was very resistant to untangling. In vitro replication by PCR was markedly reduced, and TseI restriction enzyme digestion was also hindered by the abnormal DNA structures. However, significantly, the DNA gained sensitivity to cleavage by the Type III restriction-modification enzyme, EcoP15I. CONCLUSIONS/SIGNIFICANCE: "Super-long" CAG repeats are found in a number of neurological diseases and may also appear through CAG repeat instability. We suggest that unusual DNA structures associated with super-long CAG repeats decrease transcriptional efficiency in vitro. We also raise the possibility that if these structures occur in vivo, they may play a role in the aetiology of CAG repeat diseases such as HD

Restriction endonuclease TseI cleaves A:A and T:T mismatches in CAG and CTG repeats.

The type II restriction endonuclease TseI recognizes the DNA target sequence 5'-G^CWGC-3' (where W = A or T) and cleaves after the first G to produce fragments with three-base 5'-overhangs. We have determined that it is a dimeric protein capable of cleaving not only its target sequence but also one containing A:A or T:T mismatches at the central base pair in the target sequence. The cleavage of targets containing these mismatches is as efficient as cleavage of the correct target sequence containing a central A:T base pair. The cleavage mechanism does not apparently use a base flipping mechanism as found for some other type II restriction endonuclease recognizing similarly degenerate target sequences. The ability of TseI to cleave targets with mismatches means that it can cleave the unusual DNA hairpin structures containing A:A or T:T mismatches formed by the repetitive DNA sequences associated with Huntington's disease (CAG repeats) and myotonic dystrophy type 1 (CTG repeats)

Evaluation of fluralaner and afoxolaner treatments to control flea populations, reduce pruritus and minimize dermatologic lesions in naturally infested dogs in private residences in west central Florida USA

Citation: Dryden, M. W., Canfield, M. S., Kalosy, K., Smith, A., Crevoiserat, L., McGrady, J. C., . . . Sun, F. (2016). Evaluation of fluralaner and afoxolaner treatments to control flea populations, reduce pruritus and minimize dermatologic lesions in naturally infested dogs in private residences in west central Florida USA. Parasites & Vectors, 9, 11. doi:10.1186/s13071-016-1654-7Background: A study was conducted to evaluate and compare the effectiveness of two different oral flea and tick products to control flea infestations, reduce pruritus and minimize dermatologic lesions over a 12 week period on naturally infested dogs in west central FL USA. Methods: Thirty-four dogs with natural flea infestations living in 17 homes were treated once with a fluralaner chew on study day 0. Another 27 dogs living in 17 different homes were treated orally with an afoxolaner chewable on day 0, once between days 28-30 and once again between days 54-60. All products were administered according to label directions by study investigators. Flea populations on pets were assessed using visual area counts and premise flea infestations were assessed using intermittent-light flea traps on days 0, 7, 14, 21, and once between days 28-30, 40-45, 54-60 and 82-86. Dermatologic assessments were conducted on day 0 and once monthly. Pruritus assessments were conducted by owners throughout the study. No concurrent treatments for existing skin disease (antibiotics, anti-inflammatories, anti-fungals) were allowed. Results: Following the first administration of fluralaner or afoxolaner, flea populations on pets were reduced by 99.0 % and 99.3 %, respectively within 7 days. Flea populations on the fluralaner treated dogs were 0 (100 % efficacy) on days 54-60 and 82-86 after the administration of a single dose on day 0. Administration of 3 monthly doses of afoxolaner reduced flea populations by 100 % on days 82-86. Flea numbers in indoor-premises were markedly reduced in both treatment groups by days 82-86, with 100 % and 98.9 % reductions in flea trap counts in the fluralaner and afoxolaner treatment groups, respectively. Marked improvement was observed in FAD lesion scoring, Atopic Dermatitis lesions scoring (CADESI-4) and pruritus scores with both formulations. Conclusions: In a clinical field investigation conducted during the summer of 2015 in subtropical Florida, a single administration of an oral fluralaner chew completely eliminated dog and premises flea infestations and markedly reduced dermatology lesions and pruritus. Three monthly doses of the afoxolaner chewable also eliminated flea infestations in dogs, markedly reduced premises' flea populations and similarly improved dermatology lesions and pruritus

Influence of real-world characteristics on outcomes for patients with methicillin-resistant Staphylococcal skin and soft tissue infections:a multi-country medical chart review in Europe

BACKGROUND: Patient-related (demographic/disease) and treatment-related (drug/clinician/hospital) characteristics were evaluated as potential predictors of healthcare resource use and opportunities for early switch (ES) from intravenous (IV)-to-oral methicillin-resistant Staphylococcus aureus (MRSA)-active antibiotic therapy and early hospital discharge (ED). METHODS: This retrospective observational medical chart study analyzed patients (across 12 European countries) with microbiologically confirmed MRSA complicated skin and soft tissue infections (cSSTI), ≥3 days of IV anti-MRSA antibiotics during hospitalization (July 1, 2010-June 30, 2011), and discharged alive by July 31, 2011. Logistic/linear regression models evaluated characteristics potentially associated with actual resource use (length of IV therapy, length of hospital stay [LOS], IV-to-oral antibiotic switch), and ES and ED (using literature-based and expert-verified criteria) outcomes. RESULTS: 1542 patients (mean ± SD age 60.8 ± 16.5 years; 61.5% males) were assessed with 81.0% hospitalized for MRSA cSSTI as the primary reason. Several patient demographic, infection, complication, treatment, and hospital characteristics were predictive of length of IV therapy, LOS, IV-to-oral antibiotic switch, or ES and ED opportunities. Outcomes and ES and ED opportunities varied across countries. Length of IV therapy and LOS (r = 0.66, p < 0.0001) and eligibilities for ES and ED (r = 0.44, p < 0.0001) showed relatively strong correlations. IV-to-oral antibiotic switch patients had significantly shorter length of IV therapy (−5.19 days, p < 0.001) and non-significantly shorter LOS (−1.86 days, p > 0.05). Certain patient and treatment characteristics were associated with increased odds of ES (healthcare-associated/ hospital-acquired infection) and ED (patient living arrangements, healthcare-associated/ hospital-acquired infection, initiating MRSA-active treatment 1–2 days post cSSTI index date, existing ED protocol), while other factors decreased the odds of ES (no documented MRSA culture, ≥4 days from admission to cSSTI index date, IV-to-oral switch, IV line infection) and ED (dementia, no documented MRSA culture, initiating MRSA-active treatment ≥3 days post cSSTI index date, existing ES protocol). CONCLUSIONS: Practice patterns and opportunity for further ES and ED were affected by several infection, treatment, hospital, and geographical characteristics, which should be considered in identifying ES and ED opportunities and designing interventions for MRSA cSSTI to reduce IV days and LOS while maintaining the quality of care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-476) contains supplementary material, which is available to authorized users