Here, we lay out a practical framework for such an approach, where patient subpopulations are binned based on common underlying biophysical mechanisms that drive the molecular disease pathogenesis, and we propose that this function-based approach will enable the development of targeted therapeutics that ameliorate these effects. We highlight several mutations to illustrate the need for mechanistic molecular experiments that span organizational and temporal scales, and we describe recent advances in the development of novel therapeutics based on functional targets. Finally, we describe many of the outstanding questions for the field and how fundamental mechanistic studies, informed by our more nuanced understanding of the clinical disorders, will play a central role in realizing the potential of precision medicine for genetic cardiomyopathies.
  The purpose of this paper was to study fluorescein angiography (FA) findings in eyes with lamellar macular hole (LMH), and epiretinal membrane (ERM) foveoschisis.
 
  In this prospective, observational case series, 46 eyes of patients affected by either LMH or ERM foveoschisis were examined using optical coherence tomography (OCT) and FA. All patients underwent a comprehensive ophthalmological examination and a general workup to exclude uveitis. Main outcome measures were presence of FA abnormalities, measurements of the areas of vascular leakage, and intensity of pixels in the vitreous.
 
  Twenty-four (52.2%) eyes with LMH and 22 (47.8%) with ERM foveoschisis were studied. Overall, FA abnormalities were found in 20 (83.3%) eyes with LMH and 18 (81.8%) with ERM foveoschisis. The median areas of posterior pole and peripheral leakage were 7.52 vs. 1.07 mm2 (P = 0.03) and 21.8 vs. 3.74 mm2 (P = 0.02) in the LMH and ERM foveoschisis group, respectively. Disk hyperfluorescence was found in 8 and 4 eyes and perivascular leak in 10 and 4 eyes with LMH and ERM foveoschisis, respectively. OCT-derived measurements of vitreous intensity did not differ between the two groups, and the investigational workup for uveitis was negative in all patients.
 
  Discrete areas of central and peripheral leakage are commonly found in eyes with LMH and ERM foveoschisis, whereas perivascular leak and hyperfluorescence of the disc are less frequently observed.  https://www.selleckchem.com/products/gpr84-antagonist-8.html  These findings suggest that breakdown of the retinal blood barrier, involving the posterior pole and the periphery, is frequently associated with these two vitreoretinal disorders.
 Discrete areas of central and peripheral leakage are commonly found in eyes with LMH and ERM foveoschisis, whereas perivascular leak and hyperfluorescence of the disc are less frequently observed. These findings suggest that breakdown of the retinal blood barrier, involving the posterior pole and the periphery, is frequently associated with these two vitreoretinal disorders.
  Basal linear deposit (BLinD) is a thin layer of soft drusen material. To elucidate the biology of extracellular deposits conferring age-related macular degeneration (AMD) progression risk and inform multimodal clinical imaging based on optical coherence tomography (OCT), we examined lipid content and regional prevalence of BLinD, soft drusen, pre-BLinD, and subretinal drusenoid deposit (SDD) in AMD and non-AMD aged eyes. We estimated BLinD volume and illustrated its relation to type 1 macular neovascularization (MNV).
 
  Donor eyes were classified as early to intermediate AMD (n = 25) and age-matched controls (n = 54). In high-resolution histology, we assessed BLinD/soft drusen thickness at 836 and 1716 locations in AMD and control eyes, respectively. BLinD volume was estimated using solid geometry in donor eyes, one clinically characterized.
 
  BLinD, drusen, type 1 MNV, and fluid occupy the sub-RPE-basal laminar space. BLinD volume in a 3-mm diameter circle may be as much as 0.0315 mm3. Osmophilic lipid wasm serving specialized cone and rod physiology, and its dysregulation in AMD is due to impaired transfer to the circulation.Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, clonal, complement-mediated hemolytic anemia with protean manifestations. PNH can present as a hemolytic anemia, a form of bone marrow failure, a thrombophilia, or any combination of the above. Terminal complement inhibition is highly effective for treating intravascular hemolysis from PNH and virtually eliminates the risk of thrombosis, but is not effective for treating bone marrow failure. Here, I present a variety of clinical vignettes that highlight the clinical heterogeneity of PNH and the attributes and limitations of the 2 US Food and Drug Administration-approved C5 inhibitors (eculizumab and ravulizumab) to treat PNH. I review the concept of pharmacokinetic and pharmacodynamic breakthrough hemolysis and briefly discuss new complement inhibitors upstream of C5 that are in clinical development. Last, I discuss the rare indications for bone marrow transplantation in patients with PNH.
  We present StochSS Live!, a web-based service for modeling, simulation, and analysis of a wide range of mathematical, biological and biochemical systems. Using an epidemiological model of COVID-19, we demonstrate the power of StochSS Live! to enable researchers to quickly develop a deterministic or a discrete stochastic model, infer its parameters, and analyze the results.
 
  StochSS Live! is freely available at https//live.stochss.org/.
 
  Available at https//github.com/StochSS/Covid19_Modeling.
 Available at https//github.com/StochSS/Covid19_Modeling.
  Chronic orchialgia is a frustrating urologic condition that is commonly refractory to conservative modes of therapy. Microscopic spermatic cord denervation is a proven solution for patients who do not achieve relief from nonsurgical treatments. However, current widely used techniques require additional training in microsurgery.
 
  To describe an adaptation and improvement of spermatic cord microdenervation technique that leveraged the robotic surgical training common for new urologists and is also accessible for urologists not specifically trained in microsurgery.
 
  Robotic-assisted microdenervation of the spermatic cord was performed in three patients using a fluorescence vascular imaging tool to improve visualization of vascular structures (Firefly™; Innovative Surgical, Sunnyvale, CA, USA), along with a tissue matrix allograft to allow for better healing (AminoFix™; MiMedx®, Marietta, GA, USA).
 
  All three patients (100%) experienced postoperative resolution of their chronic orchialgia, and none reported any new pain.