Effect of recombinant human nerve growth factor eye drops in patients with dry eye: a phase IIa, open label, multiple-dose study

Background: Dry eye disease (DED) affects more than 14% of the elderly population causing decrease of quality of life, high costs and vision impairment. Current treatments for DED aim at lubricating and controlling inflammation of the ocular surface. Development of novel therapies targeting different pathogenic mechanisms is sought-after. The aim of this study is to evaluate safety and efficacy of recombinant human nerve growth factor (rhNGF) eye drops in patients with DED. Methods: Forty consecutive patients with moderate to severe DED were included in a phase IIa, prospective, open label, multiple-dose, clinical trial to receive rhNGF eye drops at 20 μg/mL (Group 1: G1) or at 4 μg/mL (Group 2: G2) concentrations, two times a day in both eyes for 28 days (NCT02101281). The primary outcomes measures were treatment-emerged adverse events (AE), Symptoms Assessment in Dry Eye (SANDE) scale, ocular surface staining and Schirmer test. Results: Of 40 included patients, 39 completed the trial. Both tested rhNGF eye drop concentrations were safe and well tolerated. Twenty-nine patients experienced at least one AE (14 in G1 and 15 in G2), of which 11 had at least 1 related AE (8 in G1 and 3 in G2). Both frequency and severity of DED symptoms and ocular surface damage showed significant improvement in both groups, while tear function improved only in G1. Conclusions: The data of this study indicate that rhNGF eye drops in both doses is safe and effective in improving symptoms and signs of DED. Randomised clinical trials are ongoing to confirm the therapeutic benefit of rhNGF in DED. Trial registration number: NCT02101281

Long-term clinical efficacy of topical treatment with recombinant human nerve growth factor in neurotrophic keratopathy: a novel cure for a rare degenerative corneal disease?

Background Neurotrophic keratopathy (NK) is a rare, degenerative ocular disease characterized by reduction or loss of corneal sensitivity and development of non-healing corneal epithelial defects and ulcers. Cenegermin, a recombinant human nerve growth factor (rhNGF) eye drop solution, is the first drug approved for the treatment of NK. The aim of our study is to evaluate the long-term efficacy of this innovative topical treatment in patients with NK. Methods Retrospective, consecutive, observational case series study from a single-center setting (Department of Sense Organs, University Sapienza of Rome, Rome, Italy). 18 patients with diagnosis of stage 2 or 3 NK, treated with Cenegermin 20 mcg/ml eye drops were followed for up to 48 months. Recurrence of lesion during follow-up was evaluated at 12, 24, 36, and 48 months. In addition, corneal sensitivity, Schirmer tear test, and visual acuity (VA) were recorded at baseline, end of treatment, and at 12, 24, 36, and 48 months. Results Three patients experienced recurrence of persistent epithelial defects (PEDs) within 12 months and one patient experienced recurrence of a corneal ulcer within 36 months. Corneal sensitivity was significantly improved at all timepoints (P < 0.05). Significant improvements in visual acuity and tear production were seen at the completion of treatment as well as at 12, 24, and 36 months (P < 0.05) when compared to baseline. Conclusions A single 8-week treatment regimen of Cenegermin eye drops has clinical efficacy that can persist for up to 48 months. The long-term clinical utility of treatment with Cenegermin for NK was demonstrated through the low rate of lesion recurrence along with improvements in corneal sensitivity and tear production

Open reduction and internal fixation combined with hinged elbow fixator in capitellum and trochlea fractures: a retrospective study of 15 patients followed for 29 months

Background and purpose The current surgical treatment for displaced fracture of the capitellum and trochlea is open reduction and internal fixation (ORIF), but the results are often unsatisfactory, particularly with complex fractures. Furthermore, the surgical approach, the kind of osteosynthesis, and postoperative management are controversial. We evaluated the results of internal fixation combined with hinged external fixation. Methods We analyzed 15 patients with a mean age of 47 (18-65) years. Based on the Bryan-Morrey-McKee classification, the fractures were identified as type I in 6 cases and type IV in 9. Active and passive motion was started and activities of daily living were permitted on the second postoperative day. The mean follow-up time was 29 (12-49) months. Results In 13 cases, functional range of motion was obtained within 6 weeks of surgery. At final follow-up, 14 patients had a stable, pain-free elbow with a mean active range of motion of 13° to 140°. The average score on the Mayo elbow performance score was 98. Interpretation The use of the hinged fixator allows early motion of the elbow while preserving joint stability. It may have additional value in complex articular fractures when stable internal fixation cannot be obtained with ORIF, and in the presence of severe ligamentous injuries

Antioxidant activities in vitro of water and liposoluble extracts obtained by different species of edible insects and invertebrates

A new global interest in entomophagy, the practice of eating insects, and invertebrates, arise from the impellent necessity of preserving agriculture resources and to obtain a drastic reduction of the ecological impact of animal food on the planet. The composite nutritional content, direct consequences of a plant-based feeding, associated with the undoubtedly ecological properties, suggest for insects a role as sustainable and functional foods. We aim to investigate the ability of water and liposoluble extracts, obtained by 12 commercially available edible insects and two invertebrates, to display an antioxidant effect in vitro. Results show that water-soluble extracts of grasshoppers, silkworm, and crickets display the highest values of antioxidant capacity (TEAC), 5-fold higher than fresh orange juice, while evening cicada, giant water bugs, Thai zebra tarantula, and black scorpions have negligible values. Grasshoppers, African caterpillars, and crickets have the highest levels of reducing power (FRAP), double than fresh orange juice. Grasshoppers, black ants, and mealworms contain the highest levels of total polyphenols, while Thai zebra tarantula, black scorpions, and giant water bugs are positioned at the bottom of the ranking. The liposoluble fraction of silkworm, evening cicada, and African caterpillars shows highest level of TEAC, twice than olive oil, while Thai zebra tarantula, palm worm, and black ants are placed at the bottom of the ranking. Edible insects and invertebrates represent a potential source of antioxidant ingredients with an efficiency related to their taxonomy and eating habits. More evidences are needed in order to understand if the practice of eating insects and invertebrates might contribute to modulate oxidative stress in humans

Bifurcation and stability for Nonlinear Schroedinger equations with double well potential in the semiclassical limit

We consider the stationary solutions for a class of Schroedinger equations with a symmetric double-well potential and a nonlinear perturbation. Here, in the semiclassical limit we prove that the reduction to a finite-mode approximation give the stationary solutions, up to an exponentially small term, and that symmetry-breaking bifurcation occurs at a given value for the strength of the nonlinear term. The kind of bifurcation picture only depends on the non-linearity power. We then discuss the stability/instability properties of each branch of the stationary solutions. Finally, we consider an explicit one-dimensional toy model where the double well potential is given by means of a couple of attractive Dirac's delta pointwise interactions.Comment: 46 pages, 4 figure

Optical properties of the Ce and La di-telluride charge density wave compounds

The La and Ce di-tellurides LaTe$_2$ and CeTe$_2$ are deep in the charge-density-wave (CDW) ground state even at 300 K. We have collected their electrodynamic response over a broad spectral range from the far infrared up to the ultraviolet. We establish the energy scale of the single particle excitation across the CDW gap. Moreover, we find that the CDW collective state gaps a very large portion of the Fermi surface. Similarly to the related rare earth tri-tellurides, we envisage that interactions and Umklapp processes play a role in the onset of the CDW broken symmetry ground state

Direct experimental evidence of free fermion antibunching

Fermion antibunching was observed on a beam of free noninteracting neutrons. A monochromatic beam of thermal neutrons was first split by a graphite single crystal, then fed to two detectors, displaying a reduced coincidence rate. The result is a fermionic complement to the Hanbury Brown and Twiss effect for photons.Comment: 4 pages, 2 figure

Diabetic retinopathy, oxidative stress and sirtuins: an in depth look in enzymatic patterns and new therapeutic horizons

Diabetic retinopathy (DR) is one of the leading causes of blindness in the world. DR represents the most common microvascular complication of diabetes, and its incidence is constantly rising. The complex interactions between inflammation, oxidative stress, and the production of free oxygen radicals caused by prolonged exposure to hyperglycemia determine the development of DR. Sirtuins (SIRTs) are a recently discovered class of 7 histone deacetylases involved in cellular senescence, regulation of cell cycle, metabolic pathways, and DNA repair. SIRTs participate in the progress of several pathologies such as cancer, neurodegenerative and metabolic diseases. In DR, sirtuins 1,3,5 and 6 play an important role as they regulate the activation of the inflammatory response, insulin sensibility, and both glycolysis and gluconeogenesis. A wide spectrum of direct and indirect activators of SIRTs pathways (e.g. antagomiR, resveratrol, or glycyrrhizin) is currently being developed to treat the inflammatory cascade occurring in DR. We focuse on the main metabolic and inflammatory pathways involving SIRTs and DR, as well as recent evidence on SIRTs activators that may be employed as novel therapeutic approaches to DR

Functional properties of edible insects: a systematic review

: Consumption of edible insects has been widely suggested as an environmentally sustainable substitute for meat to reduce GHG emissions. However, the novel research field for edible insects rely on the content of bioactive ingredients and on the ability to induce a functional effect in humans. The goal of this manuscript was to review the available body of evidence on the properties of edible insects in modulating oxidative and inflammatory stress, platelet aggregation, lipid and glucose metabolism and weight control. A search for literature investigating the functional role of edible insects was carried out in the PUBMED database using specific keywords. A total of 55 studies, meeting inclusion criteria after screening, were divided on the basis of the experimental approach: in vitro studies, cellular models/ex vivo studies or in vivo studies. In the majority of the studies, insects demonstrated the ability to reduce oxidative stress, modulate antioxidant status, restore the impaired activity of antioxidant enzymes and reduce markers of oxidative damage. Edible insects displayed anti-inflammatory activity reducing cytokines and modulating specific transcription factors. Results from animal studies suggest that edible insects can modulate lipid and glucose metabolism. The limited number of studies focused on the assessment of anticoagulation activity of edible insects make it difficult to draw conclusions. More evidence from dietary intervention studies in humans is needed to support the promising evidence from in vitro and animal models about the functional role of edible insects consumption