Functional Recellularization of Acellular Rat Liver Scaffold by Induced Pluripotent Stem Cells: Molecular Evidence for Wnt/B-Catenin Upregulation.

BACKGROUND: Liver transplantation remains the only viable therapy for liver failure but has a severely restricted utility. Here, we aimed to decellularize rat livers to form acellular 3D bio-scaffolds suitable for seeding with induced pluripotent cells (iPSCs) as a tool to investigate the role of Wnt/β-catenin signaling in liver development and generation. METHODS: Dissected rat livers were randomly divided into three groups: I (control); II (decellularized scaffolds) and III (recellularized scaffolds). Liver decellularization was established via an adapted perfusion procedure and assessed through the measurement of extracellular matrix (ECM) proteins and DNA content. Liver recellularization was assessed through histological examination and measurement of transcript levels of Wnt/β-catenin pathway, hepatogenesis, liver-specific microRNAs and growth factors essential for liver development. Adult rat liver decellularization was confirmed by the maintenance of ECM proteins and persistence of growth factors essential for liver regeneration. RESULTS: iPSCs seeded rat decellularized livers displayed upregulated transcript expression of Wnt/β-catenin pathway-related, growth factors, and liver specification genes. Further, recellularized livers displayed restored liver-specific functions including albumin secretion and urea synthesis. CONCLUSION: This establishes proof-of-principle for the generation of three-dimensional liver organ scaffolds as grafts and functional re-establishment

Advances in the role of sacral nerve neuromodulation in lower urinary tract symptoms

Sacral neuromodulation has been developed to treat chronic lower urinary tract symptoms, resistant to classical conservative therapy. The suspected mechanisms of action include afferent stimulation of the central nervous system and modulation of activity at the level of the brain. Typical neuromodulation is indicated both in overactivity and in underactivity of the lower urinary tract. In the majority of patients, a unilateral electrode in a sacral foramen and connected to a pulse generator is sufficient to achieve significant clinical results also on long term. In recent years, other urological indications have been explored

Treatment success for overactive bladder with urinary urge incontinence refractory to oral antimuscarinics: a review of published evidence

<p>Abstract</p> <p>Background</p> <p>Treatment options for overactive bladder (OAB) with urinary urge incontinence (UUI) refractory to oral antimuscarinics include: botulinum toxin type A (BoNTA), sacral neuromodulation (SNM), and augmentation cystoplasty (AC). A standard treatment success metric that can be used in both clinical and economic evaluations of the above interventions has not emerged. Our objective was to conduct a literature review and synthesis of published measures of treatment success for OAB with UUI interventions and to identify a treatment success outcome.</p> <p>Methods</p> <p>We performed a literature review of primary studies that used a definition of treatment success in the OAB with UUI population receiving BoNTA, SNM, or AC. The recommended success outcome was compared to generic and disease-specific health-related quality-of-life (HRQoL) measures using data from a BoNTA treatment study of neurogenic incontinent patients.</p> <p>Results</p> <p>Across all interventions, success outcomes included: complete continence (n = 23, 44%), ≥ 50% improvement in incontinence episodes (n = 16, 31%), and subjective improvement (n = 13, 25%). We recommend the OAB with UUI treatment success outcome of ≥ 50% improvement in incontinence episodes from baseline. Using data from a neurogenic BoNTA treatment study, the average change in the Incontinence Quality of Life questionnaire was 8.8 (95% CI: -4.7, 22.3) higher for those that succeeded (N = 25) versus those that failed (N = 26). The average change in the SF-6D preference score was 0.07 (95% CI: 0.02, 0.12) higher for those that succeeded versus those that failed.</p> <p>Conclusion</p> <p>A treatment success definition that encompasses the many components of underlying OAB with UUI symptoms is currently not practical as a consequence of difficulties in measuring urgency. The treatment success outcome of ≥ 50% improvement in incontinence episodes was associated with a clinically meaningful improvement in disease-specific HRQoL for those with neurogenic OAB with UUI. The recommended success definition is less restrictive than a measure such as complete continence but includes patients who are satisfied with treatment and experience meaningful improvement in symptoms. A standardized measure of treatment success will be useful in clinical and health economic applications.</p

Visual performance of the Tecnis one-piece lens ZCB00

Sherein S Wahba, Riad F Riad, Fathy F Morkos, Abdallah K Hassouna, Maged M RoshdyNational Eye Hospital and Ain Shams University, Cairo, EgyptSynopsis: The aspheric, one-piece design of the Tecnis&amp;reg; ZCB00 intraocular lens provided higher mesopic contrast sensitivity and relatively constant refraction at different pupil sizes compared to the Sensar&amp;reg; AR40e.Purpose: Comparing the impact on functional vision of the aspheric Tecnis&amp;reg; ZCB00 one-piece lens compared to the spherical Sensar&amp;reg; AR40e three-piece lens.Setting: National Eye Hospital, Cairo, Egypt.Methods: In this prospective study, we implanted 32 Tecnis ZCB00 (Abbott Medical Optics, Santa Ana, CA) and 30 Sensar AR40e (Pharamacia and Upjohn LLC, North Peapack, NJ) lenses. Twenty-three patients in the ZCB00 group and 13 patients in the AR40e group provided reliable, reproducible data, and were therefore included in the statistical analysis. After 8 weeks, we measured photopic contrast sensitivity (PCS) at 85 cd/m&amp;sup2; and mesopic contrast sensitivity (MCS) at 5 cd/m&amp;sup2;. Uncorrected and best-corrected visual acuity were measured. Myopic shift was analyzed by comparing the manifest refraction spherical equivalent at 3 days and 8 weeks after surgery in the normal and dilated pupil.Results: The Tecnis ZCB00 group showed significantly better MCS than the Sensar AR40e group at a spatial frequency of six cycles per degree (cpd) (P = 0.037), but not at 3, 12, or 18 cpd (P = 0.299, P = 0.226, and P = 0.396, respectively). There were no significant differences between groups in corrected distance visual acuity (P = 0.175) or PCS at 3, 6, 12, or 18 cpd spatial frequencies (P = 0.440, P = 0.176, P = 0.365, and P = 0.251, respectively). The ZCB00 group showed less myopic shift in normal and dilated pupils between 3 days and 8 weeks after surgery compared to the AR40e group, but this difference was not significant.Conclusion: The Tecnis one-piece ZCB00 provided higher MCS at moderate spatial frequency than the three-piece Sensar AR40e, and was associated with relatively constant refraction at different pupil sizes.Keywords: Tecnis ZCB00, Sensar AR40e, contrast sensitivity, myopic shif