Somatic mutation (E17K) that constitutively activates the protein kinase AKT1 has been found in human cancer patients. We determined the role of the E17K mutation of AKT1 in lung cancer, through sequencing of AKT1 exon 4 in 105 resected, clinically annotated non-small cell lung cancer specimens. We detected a missense mutations G→A transition at nucleotide 49 (that results in the E17K substitution) in two squamous cell carcinoma (2/36) but not in adenocarcinoma (0/53). The activity of the endogenous kinase carrying the E17K mutation immunoprecipitated by tumour tissue was significantly higher compared with the wildtype kinase immunoprecipitated by the adjacent normal tissue as determined both by in vitro kinase assay using a consensus peptide as substrate and by in vivo analysis of the phosphorylation status of AKT1 itself (pT308, pS473) or of known downstream substrates such as GSK3 (pS9/S22) and p27 (T198). Immunostaining or immunoblot analysis on membrane-enriched extracts indicated that the enhanced membrane localization exhibited by the endogenous E17K-AKT1 may account for the observed increased activity of mutant E17K kinase in comparison with the wild-type AKT1 from adjacent normal tissue. In conclusion, this is the first report of AKT1 mutation in lung cancer. Our data provide evidence that, although AKT1 mutations are apparently rare in lung cancer (1.9%), the oncogenic properties of E17K-AKT1 may contribute to the development of a fraction of lung carcinoma with squamous histotype (5.5%).

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In the first month after the procedure, CXL induces a reduction in corneal volume. During the 24 months follow-up the cornea tends to recover its original volume with a persistence of the CXL efficacy.

Normal-sighted RRMS patients show a significant functional disconnection in the V-RSN. RRMS patients recovered from a previous ON show a complex reorganization of the V-RSN, including an increased functional connectivity at the level of extrastriate visual areas.

Our study shows that roughly 50% of the eyes have more than 1 D of astigmatism. The results can help hospitals plan and analyze the amount and costs of using toric IOLs in patients with corneal astigmatism.

PurposeTo check if optical biometry can detect eventual corneal power (Km) and axial length (AL) cataract surgery-related changes that could influence the refractive outcome.MethodsPatients scheduled for sequential bilateral cataract surgery between January and September 2017 were included in the present study. One hundred ninety-six eyes of 98 patients (48 males) were selected. Before surgery of the first eye, patients underwent a complete ophthalmic examination, including IOLMaster biometry; the same evaluations were repeated in both eyes the day before the fellow eye cataract surgery, performed at least 2 months after the first one. The differences in Km and AL in the first operated eyes were evaluated, and the fellow eyes were used as controls.ResultsKm differences in the operated eyes ranged from −1.97 to +0.98 diopter (D) (mean = −0.02 ± 0.36 D) (P = 0.89); in the nonoperated eyes they ranged from −0.6 to +0.7 D (mean = 0 ± 0.20 D) (P = 0.91). The AL differences (pseudophakic option) in the operated eyes ranged from −0.35 to +0.15 mm (mean = −0.10 ± 0.08 mm) (P < 0.001); with the aphakic option they ranged from −0.24 to + 0.26 mm (mean = 0.01 ± 0.08 mm) (P= 0.38). In the nonoperated eyes, the AL differences ranged from −0.04 to +0.06 mm (mean= 0 ± 0.02 mm) (P = 0.02).ConclusionsThe modern phaco-technique seems not to induce changes in Km and AL, supporting the hypothesis that the differences in AL are due to an incorrect estimation in pseudophakic eyes.Translational RelevanceThe results of our study may improve the AL measurements in pseudophakic eyes.

ABSTRACT.Purpose: To determine the accuracy of applanation tonometry in patients with corneas thinned by photorefractive keratectomy, and to correlate corneal changes with tonometric readings. Methods: The intraocular pressure was measured with Goldmann applanation tonometry in 87 patients who underwent photorefractive keratectomy before and 1, 6 and 12 months after treatment. The treatments ranged from ª1.5 to ª14 diopters (meanΩª7.6∫4.1 diopters) and the fellow eyes were used as controls. Results: In the treated eyes the intraocular pressure before surgery ranged from 11 to 26 mmHg (meanΩ17.7∫2.8 mmHg). One month after surgery it ranged from 5 to 22 mmHg (meanΩ11.9∫2.7 mmHg) with a significant underestimation (PΩ1¿10 ª33 ). Six months after surgery it ranged from 6 to 22 mmHg (meanΩ12∫3 mmHg) with a significant underestimation (PΩ5¿10 ª30 ). Twelve months after surgery it ranged from 8 to 22 mmHg (meanΩ12.7∫2.7 mmHg) with a significant underestimation (PΩ5¿10 ª31 ). Conclusions: A correcting factor should be applied when using applanation tonometry to measure intraocular pressure in patients who have undergone PRK.

Our findings support the hypothesis that CH and CRF are related to the corneal shape and thickness, and show a decrease of CH with age.