Structural Changes in Brain White Matter Tracts Associated With Overactive Bladder Revealed by Diffusion Tensor Magnetic Resonance Imaging: Findings From a Symptoms of Lower Urinary Tract Dysfunction Research Network Cross-Sectional Case-Control Study.

PURPOSE: Our objective was to investigate structural changes in brain white matter tracts using diffusion tensor imaging (DTI) in patients with overactive bladder (OAB). MATERIALS AND METHODS: Treatment-seeking OAB patients and matched controls enrolled in the cross-sectional case-control LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Neuroimaging Study received a brain DTI scan. Microstructural integrity of brain white matter was assessed using fractional anisotropy (FA) and mean diffusivity. OAB and urgency urinary incontinence (UUI) symptoms were assessed using the OAB Questionnaire Short-Form and International Consultation on Incontinence Questionnaire-Urinary Incontinence. The Lower Urinary Tract Symptoms Tool UUI questions and responses were correlated with FA values. RESULTS: Among 221 participants with evaluable DTI data, 146 had OAB (66 urinary urgency-only without UUI, 80 with UUI); 75 were controls. Compared with controls, participants with OAB showed decreased FA and increased mean diffusivity, representing greater microstructural abnormalities of brain white matter tracts among OAB participants. These abnormalities occurred in the corpus callosum, bilateral anterior thalamic radiation and superior longitudinal fasciculus tracts, and bilateral insula and parahippocampal region. Among participants with OAB, higher OAB Questionnaire Short-Form scores were associated with decreased FA in the left inferior fronto-occipital fasciculus, P < .0001. DTI differences between OAB and controls were driven by the urinary urgency-only (OAB-dry) but not the UUI (OAB-wet) subgroup. CONCLUSIONS: Abnormalities in microstructural integrity in specific brain white matter tracts were more frequent in OAB patients. More severe OAB symptoms were correlated with greater degree of microstructural abnormalities in brain white matter tracts in patients with OAB. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02485808.

Corneal immune cells as a biomarker of inflammation in multiple sclerosis: a longitudinal study.

Background: Corneal immune cells (ICs) are antigen-presenting cells that are known to increase ocular and systemic inflammatory conditions. Objective: We aimed to assess longitudinal changes in corneal IC in patients with multiple sclerosis (MS) and relation to disability and ongoing treatment. Design: Prospective observational study conducted between September 2016 and February 2020. Methods: Patients with relapsing-remitting MS (RRMS) (n = 45) or secondary progressive MS (SPMS) (n = 15) underwent corneal confocal microscopy (CCM) at baseline and 2-year follow-up for estimation of corneal IC density [dendritic cells with (DCF) (cells/mm2) or without nerve fiber contact (DCP); and non-dendritic cells with (NCF) or without nerve fiber contact (NCP)]. Optical coherence tomography, neuroimaging, and disability assessments were additionally performed. Healthy controls (n = 20) were assessed at baseline. Results: In both RRMS and SPMS compared to controls, DCP (p < 0.001 and p < 0.001, respectively) and DCF (p < 0.001 and p = 0.005) were higher and NCF (p = 0.007 and p = 0.02) was lower at baseline. DCP showed excellent performance in identifying patients with MS (sensitivity/specificity = 0.88/0.90) followed by DCF (0.80/0.75) and NCF (0.80/0.85). At follow-up compared to baseline, DCP (p = 0.01) was significantly reduced, and NCP (p = 0.004) and NCF (p = 0.04) were increased. Subgroup analysis showed that baseline NCP and NCF were significantly higher (p = 0.04-0.05) in patients who switched disease-modifying treatment, and baseline NCP (p = 0.05) was higher in patients on interferon. Conclusion: Baseline and change in corneal IC were related to axonal degeneration and treatment status. Evaluation of corneal IC using CCM may allow an assessment of ongoing inflammation, disease progression, and the effect of treatment in MS.

Corneal axonal loss as an imaging biomarker of neurodegeneration in multiple sclerosis: a longitudinal study.

Background: Resourceful endpoints of axonal loss are needed to predict the course of multiple sclerosis (MS). Corneal confocal microscopy (CCM) can detect axonal loss in patients with clinically isolated syndrome and established MS, which relates to neurological disability. Objective: To assess corneal axonal loss over time in relation to retinal atrophy, and neurological and radiological abnormalities in MS. Methods: Patients with relapsing-remitting (RRMS) (n = 68) or secondary progressive MS (SPMS) (n = 15) underwent CCM and optical coherence tomography. Corneal nerve fibre density (CNFD-fibres/mm2), corneal nerve branch density (CNBD-branches/mm2), corneal nerve fibre length (CNFL-mm/mm2) and retinal nerve fibre layer (RNFL-µm) thickness were quantified along with neurological and radiological assessments at baseline and after 2 years of follow-up. Age-matched, healthy controls (n = 20) were also assessed. Results: In patients with RRMS compared with controls at baseline, CNFD (p = 0.004) and RNFL thickness (p < 0.001) were lower, and CNBD (p = 0.003) was higher. In patients with SPMS compared with controls, CNFD (p < 0.001), CNFL (p = 0.04) and RNFL thickness (p < 0.001) were lower. For identifying RRMS, CNBD had the highest area under the receiver operating characteristic (AUROC) curve (0.99); and for SPMS, CNFD had the highest AUROC (0.95). At follow-up, there was a further significant decrease in CNFD (p = 0.04), CNBD (p = 0.001), CNFL (p = 0.008) and RNFL (p = 0.002) in RRMS; in CNFD (p = 0.04) and CNBD (p = 0.002) in SPMS; and in CNBD (p = 0.01) in SPMS compared with RRMS. Follow-up corneal nerve loss was greater in patients with new enhancing lesions and optic neuritis history. Conclusion: Progressive corneal and retinal axonal loss was identified in patients with MS, especially those with more active disease. CCM may serve as an imaging biomarker of axonal loss in MS.

MRI Tracking of Iron Oxide Labelled Canine Mesenchymal Stem Cells in Artificial Stifle Defects.

OBJECTIVES: The aim of this study was to describe ultrasmall superparamagnetic iron oxides labelling of canine adipose-derived mesenchymal stem cells (AdMSCs) and the detection and semiquantitative evaluation of the labelled cells after implantation in artificial canine stifle defects using magnetic resonance imaging. METHODS: Magnetic resonance imaging examinations of 10 paired (n = 20) cadaveric stifle joints were evaluated after creation of chondral defects and embedding of ultrasmall superparamagnetic iron oxides labelled canine mesenchymal stem cells. To prove the feasibility of the labelling for in vivo usage, Prussian blue staining, cell vitality tests and intralesional administration of labelled cells were conducted. Magnetic resonance imaging of ex vivo defects filled with different cell concentrations was obtained to depict the cell content semiquantitatively via signal intensity measurements (region of interest). RESULTS: Prussian blue staining showed that the labelling was effective. According to the vitality tests, it had no significant short-term influence on cell viability and proliferation rate. For the evaluation of the defect T2* sequences were feasible and stifle defects were visible allowing measurements of the signal intensity in all cases. Increasing the cell concentration within the chondral defects resulted in an inversely proportional, significant reduction of signal intensity according to the region of interest. CLINICAL SIGNIFICANCE: Ultrasmall superparamagnetic iron oxides labelling was effective. The detection of the AdMSCs in a complex anatomical structure like the surface of the femoral condyle was possible and the T2* signal intensity of the implant region was significantly correlated with the concentration of the AdMSCs.

Structure of the Human Respiratory Syncytial Virus M2-1 Protein in Complex with a Short Positive-Sense Gene-End RNA.

The M2-1 protein of human respiratory syncytial virus (HRSV) is a transcription anti-terminator that regulates the processivity of the HRSV RNA-dependent RNA polymerase (RdRP). Here, we report a crystal structure of HRSV M2-1 bound to a short positive-sense gene-end RNA (SH7) at 2.7 Å resolution. We identified multiple critical residues of M2-1 involved in RNA interaction and examined their roles using mutagenesis and MicroScale Thermophoresis (MST) assay. We found that hydrophobic residue Phe23 is indispensable for M2-1 to recognize the base of RNA. We also captured spontaneous binding of RNA (SH7) to M2-1 in all-atom simulations using a robust Gaussian accelerated molecular dynamics (GaMD) method. Both experiments and simulations revealed that the interactions of RNA with two separate domains of M2-1, the zinc-binding domain (ZBD) and the core domain (CD), are independent of each other. Collectively, our results provided a structural basis for RNA recognition by HRSV M2-1.

DNA barcoding of fish species reveals low rate of package mislabeling in Qatar.

DNA barcoding technique has made it possible to authenticate various species used for food and medicinal purposes. In the identification of seafood species, studies are concentrated in North America, Europe, and Asia. Elsewhere, including countries in the Middle East and North Africa, studies of this sort are scarce. This study focuses on packaged fresh or minimally processed fish fillet available at eight major supermarket chains in Qatar. A cocktail of eight primers attached with M13 tails established for fish species identification was adopted to facilitate PCR and sequencing. Sequences were compared with those available in the Barcode of Life Databases (BOLD Systems) and BLAST in NCBI databases. Among the 62 unique fish packages with resolved sequences, only three are confirmed to be mislabeled, at a rate of about 5%. Two of the substituted species are high value items while the third species was replaced by another, equally low-cost species. The relatively low rate of mislabeling in the samples is perhaps a result of strict local food safety regulations, which may have led to high consistency between the package labels and their contents.

An implementation case study. Implementation of the Indian Health Service's Resource and Patient Management System Electronic Health Record in the ambulatory care setting at the Phoenix Indian Medical Center.

The Phoenix Indian Medical Center (PIMC) has successfully implemented the Resource and Patient Management System Electronic Health Record (RPMS-EHR) in its Ambulatory Care departments. One-hundred and twenty-six providers use the system for essentially all elements of documentation, ordering, and coding. Implementation of one function at a time, in one clinical area at a time, allowed for focused training and support. Strong departmental leadership and the development of 'super-users' were key elements. Detailed assessments of each clinic prior to implementation were vital, resulting in optimal workstation utilization and a greater understanding of each clinic's unique flow. Each phase saw an increasing reluctance to revert to old paper processes. The success of this implementation has placed pressure on the remainder of the hospital to implement the RPMS-EHR, and has given the informatics team an increased awareness of what resources are required to achieve this result.