Tool Run-Out in Micro-Milling: Development of an Analytical Model Based on Cutting Force Signal Analysis.

Micro-machining is a widespread finishing process for fabricating accurate parts as biomedical devices. The continuous effort in reducing the gap between the micro- and macro-domains is connected to the transition from conventional to micro-scale machining. This process generates several undesired issues, which complicate the process's optimization, and tool run-out is one of the most difficult phenomena to experimentally investigate. This work focuses on its analytical description; in particular, a new method to calibrate the model parameters based on cutting force signal elaboration is described. Today, run-out prevision requires time-consuming geometrical measurements, and the main aim of our innovative model is to make the analysis completely free from dimensional measurements. The procedure was tested on data extrapolated from the micro-machining of additively manufactured AlSi10Mg specimens. The strategy appears promising because it is built on a strong mathematical basis, and it may be developed in further studies.

Hydrogen peroxide and viral infections: A literature review with research hypothesis definition in relation to the current covid-19 pandemic.

We reviewed the literature concerning the innate response from nasal and oral epithelial cells and their reaction to hydrogen peroxide (H2O2). Hydrogen peroxide is produced physiologically by oral bacteria and plays a significant role in the balance of oral microecology since it is an important antimicrobial agent. In the epithelial cells, the enzyme superoxide dismutase catalyzes a reaction leading from hydrogen peroxide to the ion superoxide. The induced oxidative stress stimulates a local innate response via activation of the toll-like receptors and the NF-κB. Those kinds of reactions are also activated by viral infections. Virus-induced oxidative stress plays an important role in the regulation of the host immune system and the specific oxidant-sensitive pathway is one of the effective strategies against viral infections. Therefore, nose/mouth/throat washing with hydrogen peroxide may enhance those local innate responses to viral infections and help protect against the current coronavirus pandemic. We strongly encourage the rapid development of randomized controlled trials in both SARS-CoV-2 positive and negative subjects to test the preliminary findings from the in-vitro and in-vivo observational studies that we identified.

Anterior-Segment Optical Coherence Tomography and Scanning Electron Microscopy to Evaluate Corneal Epithelial Changes in Patients Undergoing Glaucoma Therapy.

PURPOSE: To measure corneal epithelial thickness (CET) in patients with glaucoma using anterior-segment optical coherence tomography and to evaluate CET changes in relation to corneal epithelial microvilli analyzed by scanning electron microscopy (SEM). METHODS: Twenty-two eyes (16 patients) being treated with preservative-containing topical medications and 12 normal eyes underwent anterior-segment optical coherence tomography imaging using RTVue-100. The CET maps generated corresponded to a 6-mm diameter area of cornea that was divided into 17 sectors. We compared the CETs of each sector obtained in the glaucomatous group with those obtained in the control group. RESULTS: Glaucomatous eyes were divided into 2 groups based on the number of microvilli on SEM: group 1 (6 eyes) = grades 1 and 2 at SEM (range: 500-3000) and group 2 (10 eyes) = grades 3 and 4 at SEM (range: 0-500). Four CET sectors were significantly thinner in group 1 than in normal eyes: central (P = 0.012), superior (P = 0.005), temporal paracentral (P = 0.003), and temporal midperipheral (P = 0.023). No significant differences were observed between group 2 and normal eyes. CET sectors were significantly thinner in group 1 than in group 2 only in the superior (P = 0.024) and superior-temporal paracentral (P = 0.020) sectors. CET progressively increased in patients with glaucoma as the number of corneal epithelial microvilli decreased. CONCLUSIONS: CET and corneal epithelial microvilli are new parameters with which to evaluate early stages of corneal epithelial changes during glaucoma therapy. In advanced stages of corneal epithelial damage, SEM evaluation reveals ultrastructural epithelial changes that may not be observed on CET measurements.

Corneal Cross-Linking: Evaluating the Potential for a Lower Power, Shorter Duration Treatment.

PURPOSE: To determine the cross-linking effect of a riboflavin ultraviolet-A (UV-A) corneal cross-linking treatment that is both shorter and has lower energy than the Dresden protocol. METHODS: In a first experiment, 12 human corneas were presoaked with riboflavin and then irradiated with UV-A at 3 mW/cm after clearing the surface of riboflavin, with no added riboflavin during irradiation. Percent UV-A transmission through the corneas was measured at intervals up to 30 minutes. A second experiment involved 24 porcine corneas. Eight were de-epithelialized, presoaked in riboflavin for 30 minutes, and irradiated at 1.5 mW/cm for 10 minutes. An additional 8 were riboflavin treated and similarly irradiated, but with epithelium intact and a final 8 corneas were not treated. Young modulus was measured in all 24 corneas at the end of the experiment. RESULTS: The first experiment showed essentially complete riboflavin oxidation after only 10 minutes. Based on these results, a shortened UV-A exposure cross-linking experiment was designed using a reduced UV-A fluence of 1.5 mW/cm, an endothelial exposure within safety limits in humans. With this protocol Young modulus was the same in the irradiated porcine corneas but with epithelium intact as in the untreated corneas. In contrast, Young modulus increased by a factor of 1.99 in the UV-A cross-linked corneas at 1.5 mW/cm for 10 minutes with the epithelium removed. CONCLUSIONS: A shorter, lower energy protocol than the Dresden protocol seems to provide a significant increase in Young modulus, similar to published results with higher energy, longer exposure protocols.

Study on the Protective Effect of a New Manganese Superoxide Dismutase on the Microvilli of Rabbit Eyes Exposed to UV Radiation.

We present a study on the protective effects against UV radiation of a gel formulation containing a new recombinant form of manganese superoxide dismutase on the conjunctiva and corneal epithelia of rabbit eyes. The integrity of the microvilli of both ocular tissues has been considered as an indicator of the health of the tissues. Samples, collected by impression cytology technique, were added of 80 µL of a gel formulation containing superoxide dismutase (2.0 µg/mL) and irradiated with UV rays for 30 minutes and were evaluated with scanning electron microscopy. Wilcoxon test was used to verify the possible occurrence of statistically significant differences between damage for treated and nontreated tissues. Application of gel produces a significant reduction of damage by UV irradiation of ocular epithelia; both epithelia present a significant reduction of damaged microvilli number if treated with the superoxide dismutase gel formulation: the p values (differences between damage found for treated and nontreated both ocular tissues) for conjunctiva and cornea samples were p ≪ 0.01 and p ≪ 0.0001, respectively, at confidence level of 95%. The administration of this gel formulation before UV exposure plays a considerable protective role in ocular tissues of rabbit eye with a significant reduction of the damage.

Enhancement of corneal permeation of riboflavin-5'-phosphate through vitamin E TPGS: a promising approach in corneal trans-epithelial cross linking treatment.

Corneal accumulation of riboflavin-5'-phosphate (riboflavin) is an essential step in the so called corneal cross-linking (CXL), an elective therapy for the treatment of progressive keratoconus, corneal ectasia and irregular astigmatism. CXL is usually performed after surgical debridement of corneal epithelium, since it impedes the stromal penetration of riboflavin in a relatively short time. d-Alpha-tocopheryl poly(ethylene glycol) 1000 succinate (VE-TPGS) is an effective permeation enhancer used to increase adsorption of drugs trough different biological barriers. Moreover, belonging to the group of tocopherol pro-drugs, VE-TPGS exerts a protective effect on biological membrane against free-radical damage. The aim of this work is the evaluation of VE-TPGS effects on riboflavin corneal permeability, and the assessment of its protective effect against free-radicals generated during CXL procedures. Different solutions containing riboflavin (0.125% w/w), dextran (20.0% w/w) and increasing concentration of VE-TPGS were tested. Corneal permeation was evaluated in vitro by the use of modified Franz-cell type diffusion cells and freshly excised porcine corneas as barrier. The effect of VE-TPGS on riboflavin corneal penetration was compared with a standard commercial solution of riboflavin in dextran at different times. Accumulation experiments were conducted both on epithelized and non-epithelized corneas. Moreover, epithelized porcine corneas, treated with the tested solutions, were subjected to an in vitro CXL procedure versus non-epithelized corneas, treated with a commercial solution of riboflavin. Differences were measured by means of corneal rigidity using Young's modulus. The photo-protective effect of tested solutions on corneal epithelium was, finally, evaluated. CXL treatment was applied, in vitro, on human explanted corneas and resulting morphology of corneal epithelium was investigated by scanning electron microscopy.

Scanning electron microscopy of corneal epithelium in soft contact lens wearers.

PURPOSE: To use scanning electron microscopy (SEM) to assess differences in corneal epithelium features between soft contact lens (CL) wearers and non-CL wear control. METHODS: In a cross-sectional survey, the corneal epithelium removed before photorefractive keratectomy in 10 soft CL wearers (10 eyes) and in 10 non-CL wearers (10 eyes) was evaluated with SEM. The aim of the study was to assess ultrastructural differences in corneal epithelium between the 2 groups. RESULTS: No statistically significant difference was present between the 2 groups as concerns the number of microvilli (P = 0.19). An amount of epithelial mucus >20% was detected in 20% of soft CL wearers and in 80% of non-CL wearers (P = 0.01). A good tolerance to CL was referred by CL wearers. CONCLUSION: A significant reduction of epithelial mucus at SEM evaluation was present in the CL wearers even in absence of complaints referred to CL.

Allergic conjunctivitis and latent infections.

PURPOSE: The purpose of this study was to evaluate in a large series the incidence of latent infection during chronic allergic conjunctivitis. METHODS: In a 5-year follow-up prospective, nonrandomized trial, we evaluated 236 patients (472 eyes) with a history of allergic conjunctivitis but without evidence of infection. Conjunctival scrapings were examined cytologically, and antibiograms and antimicrograms were assessed. The 472 eyes were divided into 5 subgroups based on the percent of eosinophilic cells in conjunctival specimens. RESULTS: Latent concurrent infection was identified in 176 of 472 eyes (37%): Candida albicans (55.2%), Staphylococcus epidermidis (50.9%), Chlamydia trachomatis (30.7%), and Staphylococcus aureus (23%). The incidence of concurrent infection (mainly bacterial infection) strongly correlated with the percent of eosinophilic cells. Concurrent bacterial infection was identified in 26 of 26 cases of the subgroup with the highest percent of eosinophilic cells. CONCLUSION: Chronic allergic conjunctivitis may be associated with latent infection. Pathogens can stimulate activation of eosinophils with a consequent worsening and chronicity of allergic symptoms.

Slime-producing Staphylococcus epidermidis and S. aureus in acute bacterial conjunctivitis in soft contact lens wearers.

In recent years, an increase in ocular pathologies related to soft contact lens has been observed. The most common infectious agents were Staphylococcus spp. Some strains produce an extracellular polysaccharidic slime that can cause severe infections. Polysaccharide synthesis is under genetic control and involves a specific intercellular adhesion (ica) locus, in particular, icaA and icaD genes. Conjunctival swabs from 97 patients with presumably bacterial bilateral conjunctivitis, wearers of soft contact lenses were examined. We determined the ability of staphylococci to produce slime, relating it to the presence of icaA and icaD genes. We also investigated the antibiotic susceptibility and Pulsed Field Gel Electrophoresis (PFGE) patterns of the clinical isolates. We found that 74.1% of the S. epidermidis strains and 61.1% of the S. aureus strains isolated were slime producers and showed icaA and icaD genes. Both S. epidermidis and S. aureus slime-producing strains exhibited more surface hydrophobicity than non-producing slime strains. The PFGE patterns overlapped in S. epidermidis strains with high hydrophobicity. The similar PFGE patterns were not related to biofilm production. We found scarce matching among the Staphylococcus spp. studied, slime production, surface hydrophobicity and antibiotic susceptibility.

Effect of 0.005% latanoprost once daily on intraocular pressure in glaucomatous patients not adequately controlled by beta-blockers twice daily: a 3-year follow-up. Experience and incidence of side effects in a prospective study on 76 patients.

PURPOSE: To assess the efficacy and side effects of 0.005% latanoprost once daily during 3 years of treatment in glaucomatous patients in whom intraocular pressure (IOP) was not adequately controlled by beta-blockers twice daily. METHODS: An unmasked prospective study was performed on 76 glaucomatous patients (145 eyes) treated with 0.005% latanoprost at bedtime, after a 21-day wash-out period from beta-blockers. IOP measurement and visual field examination were recorded over the follow-up period. RESULTS: Latanoprost significantly reduced IOP from 26.5+/-6.6 mmHg (mean +/- SD) to 17.4+/-2.7 mmHg after 36 months of treatment in 48 patients (63.1%), who completed the trial. Twenty-eight patients (36.8%) discontinued the therapy. In 12 patients (15.8%) the treatment did not obtain a satisfactory target IOP. In two subjects (2.6%), despite the IOP reduction, visual field damage progressed. The remaining 10 patients (13.1%) discontinued the treatment because of the following side effects: microfollicular conjunctivitis (seven cases); severe oedema of conjunctiva and eyelids (one case); corneal punctate erosion (one case); cystoid macular oedema (one case). No flare or pigmentary changes of iris and eyelash were observed. CONCLUSION: Latanoprost 0.005% once daily significantly reduces IOP in the majority of glaucomatous patients uncontrolled by beta-blockers. The reduction of IOP was statistically significant during 3 years of follow-up, confirming the clinical efficacy of this compound. The ocular side effects requiring cessation of therapy were mainly allergic reactions. The most severe adverse effects were one case of corneal punctate erosion and one case of cystoid macular oedema in a pseudophakic patient.

Pharmacokinetics of cetirizine in tear fluid after a single oral dose.

BACKGROUND: Antihistamines (histamine H(1) receptor antagonists) are effective and convenient drugs for the treatment of allergic conjunctivitis. Because of the short duration of action generally observed for drugs administered topically to the eye, the oral route is often preferred. However, the presence of a selective barrier between blood and ocular tissues, the so-called blood-ocular barrier, does not allow a priori assessment of the most suitable dosage for ocular therapy. OBJECTIVE: To investigate the tear concentrations of cetirizine, a second-generation antihistamine, over time following oral administration, and to study the relationship between plasma and tear fluid concentrations. DESIGN AND PARTICIPANTS: Pharmacokinetic study of a single oral dose of cetirizine 10mg in 40 patients treated for allergic conjunctivitis. METHODS: Patients received a single oral dose of cetirizine. Samples of blood and tear fluid were taken according to predefined sampling schedules and the concentrations of cetirizine were determined by a new high performance liquid chromatography method. RESULTS: Concentration-time profiles for cetirizine in serum and tear fluid were similar, although the mean maximum concentration in tear fluid was reached later than in serum (90 and 30 min, respectively). However, at 60 and 120 min the cetirizine concentration in tear fluid was 98 and 92% of the mean maximum concentration, respectively, showing a plateau region and indicating that the disposition rate for the tear fluid compartment was very similar to that for the blood compartment. CONCLUSION: Oral administration of cetirizine yields therapeutically effective concentrations of the drug at the anterior surface of the eye.