Novel heterozygous variant identified in a patient with spinocerebellar ataxia type 14 and macular dystrophy.

Purpose: To report on a patient with spinocerebellar ataxia type 14 (SCA14) and macular dystrophy with identification of a novel variant.

Methods: Case report.

Results: A 63-year-old female with molecularly confirmed SCA14 presented with symmetric pigmentary disturbances in a perifoveal distribution resembling a pattern macular dystrophy.

Gene therapy for cross-correction of somatic organs and the CNS in mucopolysaccharidosis II in rodents and non-human primates.

Mucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by deficient activity of iduronate-2-sulfatase (I2S), leading to pathological accumulation of glycosaminoglycans (GAGs) in tissues. We used iduronate-2-sulfatase knockout ( KO) mice to investigate if liver-directed recombinant adeno-associated virus vectors (rAAV8-LSP-h) encoding human I2S (hI2S) could cross-correct I2S deficiency in KO mouse tissues, and we then assessed the translation of mouse data to non-human primates (NHPs). Treated mice showed sustained hepatic hI2S production, accompanied by normalized GAG levels in somatic tissues (including critical tissues such as heart and lung), indicating systemic cross-correction from liver-secreted hI2S.

Effect of Macular Internal Limiting Membrane Peeling on Single Surgery Success Rates of Vitrectomy for Uncomplicated, Primary Macula-Off Retinal Detachment.

To determine the anatomic and visual outcomes of pars plana vitrectomy for uncomplicated, primary macula-off rhegmatogenous retinal detachment (RRD) with and without internal limiting membrane (ILM) peeling. This retrospective chart review comprised 129 patients with uncomplicated, primary macula-off RRD presenting between January 1, 2016, and May 31, 2021. Thirty-six patients (27.

PHACOVITRECTOMY FOR PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT REPAIR: A Retrospective Review.

Purpose: To analyze the single surgery success rate and anterior segment complications related to phacoemulsification and intraocular lens implantation in a series of patients undergoing phacovitrectomy for all types of primary rhegmatogenous retinal detachment.

Methods: We performed a retrospective interventional case series on 302 eyes undergoing phacovitrectomy for primary rhegmatogenous retinal detachment repair between November 1, 2016, and February 2, 2019, in Edmonton, Canada. Primary outcomes included single surgery retinal reattachment rate and anterior segment complications.

Fragmentation of Human Neutrophil α-Defensin 4 to Combat Multidrug Resistant Bacteria.

The occurrence and spread of multidrug-resistant bacteria is a prominent health concern. To curb this urgent threat, new innovative strategies pursuing novel antimicrobial agents are of the utmost importance. Here, we unleashed the antimicrobial activity of human neutrophil peptide-4 (HNP-4) by tryptic digestion.

Leveraging Quantitative Systems Pharmacology Approach into Development of Human Recombinant Follistatin Fusion Protein for Duchenne Muscular Dystrophy.

Quantitative understanding about the dynamics of drug-target interactions in biological systems is essential, especially in rare disease programs with small patient populations. Follistatin, by antagonism of myostatin and activin, which are negative regulators of skeletal muscle and inflammatory response, is a promising therapeutic target for Duchenne Muscular Dystrophy. In this study, we constructed a quantitative systems pharmacology model for FS-EEE-Fc, a follistatin recombinant protein to investigate its efficacy from dual target binding, and, subsequently, to project its human efficacious dose.

Wheat Consumption Aggravates Colitis in Mice via Amylase Trypsin Inhibitor-mediated Dysbiosis.

Background & Aims: Wheat has become the world's major staple and its consumption correlates with prevalence of noncommunicable disorders such as inflammatory bowel diseases. Amylase trypsin inhibitors (ATIs), a component of wheat, activate the intestine's innate immune response via toll-like receptor 4 (TLR4). We investigated the effects of wheat and ATIs on severity of colitis and fecal microbiota in mice.

The human α-defensin-derived peptide HD5(1-9) inhibits cellular attachment and entry of human cytomegalovirus.

Human cytomegalovirus (HCMV) infection causes severe illness in newborns and immunocompromised patients. Since treatment options are limited there is an unmet need for new therapeutic approaches. Defensins are cationic peptides, produced by various human tissues, which serve as antimicrobial effectors of the immune system.

Comparison of Residual Subfoveal Fluid by Intraoperative OCT After Macula-Involving RRD Repair Using Direct Drainage, Drainage Retinotomy, or Perfluoro-n-Octane.

Background And Objective: This study evaluated the residual subfoveal fluid (SFF) immediately after rhegmatogenous retinal detachment (RRD) repair using intraoperative optical coherence tomography (iOCT).

Patients And Methods: This retrospective cohort study assessed fovea-involving RRD repaired by pars plana vitrectomy (PPV) using different drainage techniques. iOCT images were acquired through the fovea at the start of the case prior to initiating vitrectomy and then again immediately prior to introduction of tamponade.

Proteolytic Degradation of reduced Human Beta Defensin 1 generates a Novel Antibiotic Octapeptide.

Microbial resistance against clinical used antibiotics is on the rise. Accordingly, there is a high demand for new innovative antimicrobial strategies. The host-defense peptide human beta-defensin 1 (hBD-1) is produced continuously by epithelial cells and exhibits compelling antimicrobial activity after reduction of its disulphide bridges.

Are the changes in diagnostic criteria for gestational diabetes mellitus reflected in perinatal outcomes? A retrospective assessment.

Background: Gestational diabetes mellitus (GDM) is glucose intolerance first diagnosed during pregnancy not due to overt diabetes. Recent changes to the diagnostic guidelines have been shown to increase the apparent occurrence of GDM.

Aim: The aim of this study was to compare retrospectively the neonatal outcomes between groups defined using the new and old criteria to assess the impact of guideline changes on pregnancy outcomes.

Paneth cell α-defensins HD-5 and HD-6 display differential degradation into active antimicrobial fragments.

Antimicrobial peptides, in particular α-defensins expressed by Paneth cells, control microbiota composition and play a key role in intestinal barrier function and homeostasis. Dynamic conditions in the local microenvironment, such as pH and redox potential, significantly affect the antimicrobial spectrum. In contrast to oxidized peptides, some reduced defensins exhibit increased vulnerability to proteolytic degradation.

Myostatin and activin blockade by engineered follistatin results in hypertrophy and improves dystrophic pathology in mdx mouse more than myostatin blockade alone.

Background: Myostatin antagonists are being developed as therapies for Duchenne muscular dystrophy due to their strong hypertrophic effects on skeletal muscle. Engineered follistatin has the potential to combine the hypertrophy of myostatin antagonism with the anti-inflammatory and anti-fibrotic effects of activin A antagonism.

Methods: Engineered follistatin was administered to C57BL/6 mice for 4 weeks, and muscle mass and myofiber size was measured.

β-Defensin 1 Is Prominent in the Liver and Induced During Cholestasis by Bilirubin and Bile Acids Farnesoid X Receptor and Constitutive Androstane Receptor.

Background & Aims: Knowledge about innate antimicrobial defense of the liver is limited. We investigated hepatic expression and regulation of antimicrobial peptides with focus on the human beta defensin-1 (hBD-1).

Methods: Radial diffusion assay was used to analyze antimicrobial activity of liver tissue.

TOPICAL DORZOLAMIDE-TIMOLOL WITH INTRAVITREOUS ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR FOR RETINAL VEIN OCCLUSION: A PILOT STUDY.

Purpose: To evaluate topical dorzolamide hydrochloride-timolol maleate as an adjunct therapy to intravitreous anti-vascular endothelial growth factor injections in eyes with retinal vein occlusion resistant to treatment.

Methods: Retinal vein occlusion patients with a history of persistent macular edema, despite fixed-interval intravitreous anti-vascular endothelial growth factor injections, were enrolled between April 4, 2016, and June 4, 2017. On enrollment, patients were instructed to administer one drop of topical dorzolamide-timolol twice daily for the duration of the study.

Protein Engineering on Human Recombinant Follistatin: Enhancing Pharmacokinetic Characteristics for Therapeutic Application.

Follistatin (FS) is an important regulatory protein, a natural antagonist for transforming growth factor-β family members activin and myostatin. The diverse biologic roles of the activin and myostatin signaling pathways make FS a promising therapeutic target for treating human diseases exhibiting inflammation, fibrosis, and muscle disorders, such as Duchenne muscular dystrophy. However, rapid heparin-mediated hepatic clearance of FS limits its therapeutic potential.

Patient Comfort with Yellow (577 nm) vs. Green (532 nm) Laser Panretinal Photocoagulation for Proliferative Diabetic Retinopathy.

Purpose: Pain associated with panretinal photocoagulation (PRP) can adversely affect the number and quality of retinal burns delivered and subsequently increase the number of treatment sessions required to achieve regression of proliferative diabetic retinopathy (PDR). We assessed comfort in patients undergoing treatment with yellow (577 nm) vs. green (532 nm) PRP for PDR.

Bacterial Periplasmic Oxidoreductases Control the Activity of Oxidized Human Antimicrobial β-Defensin 1.

The antimicrobial peptide human β-defensin 1 (hBD1) is continuously produced by epithelial cells in many tissues. Compared to other defensins, hBD1 has only minor antibiotic activity in its native state. After reduction of its disulfide bridges, however, it becomes a potent antimicrobial agent against bacteria, while the oxidized native form (hBD1ox) shows specific activity against Gram-negative bacteria.