Pachyonychia congenita and botulinum toxin Thomas, B.R.; Sahota, A.
British journal of dermatology (1951),
March 2020, 2020-Mar, 2020-03-00, 20200301, Letnik:
182, Številka:
3
Journal Article
Recenzirano
Linked Article: Koren et al. Br J Dermatol 2020; 182:671–677.
Iaccarino et al. (2016) 1 exposed 1 h of light flickering at 40 Hz to awake 5XFAD Alzheimer’s Disease (AD) mouse models, generating action potentials at 40 Hz, activating ∼54% of microglia to ...colocalize with Aβ plaque, acutely, and clearing ∼ 50% of Aβ plaque after seven days, but only in the visual cortex.
Transcranially delivered, focused ultrasound (tFUS) can replicate the results of Iaccarino et al. (2016) 1 but throughout its area of application.
We exposed sedated 5XFAD mice to tFUS (2.0 MHz carrier frequency, 40 Hz pulse repetition frequency, 400 μs-long pulses, spatial peak pulse average value of 190 W/cm2). Acute studies targeted tFUS into one hemisphere of brain centered on its hippocampus for 1 h. Chronic studies targeted comparable brain in each hemisphere for 1 h/day for five days.
Acute application of tFUS activated more microglia that colocalized with Aβ plaque relative to sham ultrasound (36.0 ± 4.6% versus 14.2 ± 2.6% mean ± standard error, z = 2.45, p < 0.014) and relative to the contralateral hemisphere of treated brain (36.0 ± 4.6% versus 14.3 ± 4.0%, z = 2.61, p < 0.009). Chronic application over five days reduced their Aβ plaque burden by nearly half relative to paired sham animals (47.4 ± 5.8%, z = - 2.79, p < 0.005).
Our results compare to those of Iaccarino et al. (2016) 1 but throughout the area of ultrasound-exposed brain. Our results also compare to those achieved by medications that target Aβ, but over a substantially shorter period of time. The proximity of our ultrasound protocol to those shown safe for non-human primates and humans may motivate its rapid translation to human studies.
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•Ultrasound-activation of brain can activate microglia to attack Aβ plaque and clear Aβ plaque, in vivo.•Aβ plaque clearance amount rivals that of medications, but on a much faster time scale.•This study used near-diagnostic ultrasound, making its translation to human studies a plausibly quick affair.
Background
Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are ...missing.
Objectives
The goal of these evidence‐ and consensus‐based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus‐based recommendations for the histopathological definition, diagnosis and the assessment of patients.
Methods
The guidelines development followed a pre‐defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies.
Results
Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately.
Conclusions
International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).
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