Several lines of evidence suggest that neurotrophin administration may be of some therapeutic benefit in the treatment of peripheral neuropathy. However, a third of sensory neurons do not express receptors for the neurotrophins. These neurons are of small diameter and can be identified by the binding of the lectin IB4 and the expression of the enzyme thiamine monophosphatase (TMP). Here we show that these neurons express the receptor components for glial-derived neurotrophic factor (GDNF) signaling (RET, GFRalpha-1, and GFRalpha-2). In lumbar dorsal root ganglia, virtually all IB4-labeled cells express RET mRNA, and the majority of these cells (79%) also express GFRalpha-1, GFRalpha-2, or GFRalpha-1 plus GFRalpha-2. GDNF, but not nerve growth factor (NGF), can prevent several axotomy-induced changes in these neurons, including the downregulation of IB4 binding, TMP activity, and somatostatin expression. GDNF also prevents the slowing of conduction velocity that normally occurs after axotomy in a population of small diameter DRG cells and the A-fiber sprouting into lamina II of the dorsal horn. GDNF therefore may be useful in the treatment of peripheral neuropathies and may protect peripheral neurons that are refractory to neurotrophin treatment.

The on-demand digital healthcare ecosystem is on the near horizon. It has the potential to extract a wealth of information from “big data” collected at the population level, to enhance preventive and precision medicine at the patient level. This may improve efficiency and quality while decreasing cost of healthcare delivered by professionals. However, there are still security and privacy issues that need to be addressed before algorithms, data, and models can be mobilized safely at scale. In this paper we discuss how distributed ledger technologies can play a key role in advancing electronic health, by ensuring authenticity and integrity of data generated by wearable and embedded devices. We demonstrate how the Masked Authenticated Messaging extension module of the IOTA protocol can be used to securely share, store, and retrieve encrypted activity data using a tamper-proof distributed ledger.

Background:Transrectal prostate biopsy has limited diagnostic accuracy. Prostate Imaging Compared to Transperineal Ultrasound-guided biopsy for significant prostate cancer Risk Evaluation (PICTURE) was a paired-cohort confirmatory study designed to assess diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) in men requiring a repeat biopsy.Methods:All underwent 3 T mpMRI and transperineal template prostate mapping biopsies (TTPM biopsies). Multiparametric MRI was reported using Likert scores and radiologists were blinded to initial biopsies. Men were blinded to mpMRI results. Clinically significant prostate cancer was defined as Gleason ⩾4+3 and/or cancer core length ⩾6 mm.Results:Two hundred and forty-nine had both tests with mean (s.d.) age was 62 (7) years, median (IQR) PSA 6.8 ng ml (4.98–9.50), median (IQR) number of previous biopsies 1 (1–2) and mean (s.d.) gland size 37 ml (15.5). On TTPM biopsies, 103 (41%) had clinically significant prostate cancer. Two hundred and fourteen (86%) had a positive prostate mpMRI using Likert score ⩾3; sensitivity was 97.1% (95% confidence interval (CI): 92–99), specificity 21.9% (15.5–29.5), negative predictive value (NPV) 91.4% (76.9–98.1) and positive predictive value (PPV) 46.7% (35.2–47.8). One hundred and twenty-nine (51.8%) had a positive mpMRI using Likert score ⩾4; sensitivity was 80.6% (71.6–87.7), specificity 68.5% (60.3–75.9), NPV 83.3% (75.4–89.5) and PPV 64.3% (55.4–72.6).Conclusions:In men advised to have a repeat prostate biopsy, prostate mpMRI could be used to safely avoid a repeat biopsy with high sensitivity for clinically significant cancers. However, such a strategy can miss some significant cancers and overdiagnose insignificant cancers depending on the mpMRI score threshold used to define which men should be biopsied.

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Objectives To determine the diagnostic accuracy and interobserver concordance of whole-body (WB)-MRI, vs. 99m Tc bone scintigraphy (BS) and 18 fluoro-ethyl-choline ( 18 F-choline) PET/CT for the primary staging of intermediate/high-risk prostate cancer. Methods An institutional review board approved prospective cohort study carried out between July 2012 and November 2015, whereby 56 men prospectively underwent 3.0-T multiparametric (mp)-WB-MRI in addition to BS (all patients) ± 18 F-choline PET/CT (33 patients). MRI comprised pre- and post-contrast modified Dixon (mDixon), T2-weighted (T2W) imaging, and diffusion-weighted imaging (DWI). Patients underwent follow-up mp-WB-MRI at 1 year to derive the reference standard. WB-MRIs were reviewed by two radiologists applying a 6-point scale and a locked sequential read (LSR) paradigm for the suspicion of nodal (N) and metastatic disease (M1a and M1b). Results The mean sensitivity/specificity of WB-MRI for N1 disease was 1.00/0.96 respectively, compared with 1.00/0.82 for 18 F-choline PET/CT. The mean sensitivity and specificity of WB-MRI, 18 F-choline PET/CT, and BS were 0.90/0.88, 0.80/0.92, and 0.60/1.00 for M1b disease. ROC-AUC did not show statistically significant improvement for each component of the LSR; mean ROC-AUC 0.92, 0.94, and 0.93 ( p < 0.05) for mDixon + DWI, + T2WI, and + contrast respectively. WB-MRI had an interobserver concordance ( κ ) of 0.79, 0.68, and 0.58 for N1, M1a, and M1b diseases respectively. Conclusions WB-MRI provides high levels of diagnostic accuracy for both nodal and metastatic bone disease, with higher levels of sensitivity than BS for metastatic disease, and similar performance to 18 F-choline PET/CT. T2 and post-contrast mDixon had no significant additive value above a protocol comprising mDixon and DWI alone. Key Points • A whole-body MRI protocol comprising unenhanced mDixon and diffusion-weighted imaging provides high levels of diagnostic accuracy for the primary staging of intermediate- and high-risk prostate cancer. • The diagnostic accuracy of whole-body MRI is much higher than that of bone scintigraphy, as currently recommended for clinical use. • Staging using WB-MRI, rather than bone scintigraphy, could result in better patient stratification and treatment delivery than is currently provided to patients worldwide. Electronic supplementary material The online version of this article (10.1007/s00330-018-5813-4) contains supplementary material, which is available to authorized users.