ULTRASOUND MEASUREMENTS OF THE DISTANCE BETWEEN LIMBUS AND RETINAL BREAK IN EYES WITH MEDIA OPACITIES.

PURPOSE: To assess the reproducibility and accuracy of ultrasound (US) measurements in determining the distance between corneoscleral limbus and retinal break and its relation with the distance measured by indirect ophthalmoscopy, in patients undergoing a laser retinopexy procedure. METHODS: Forty-four patients with a single retinal break, scheduled for laser a retinopexy procedure (26 phakic patients and 18 pseudophakic patients), underwent 5 repeated measurements by high-resolution US and 3 measurements (at the time of the laser procedure, 1 and 3 months) by indirect ophthalmoscopy with scleral indentation of the corneoscleral limbus-retinal break distance with a caliper. RESULTS: In the phakic patients group, measurements ranged from 8.75 mm to 14.45 mm (12.56 ± 1.24, mean ± SD) and from 9.5 mm to 15 mm (12.35 ± 1.32) with US and indirect ophthalmoscopy, respectively. In the pseudophakic patients group, measurements ranged from 9.04 mm to 13.95 mm (11.88 ± 1.33) and from 8.5 mm to 13.2 mm (11.93 ± 0.99) with US and indirect ophthalmoscopy, respectively. The correlation coefficient was greater than 0.97. Measurement variability was very small. In phakic eyes, it was 0.13 ± 0.08 mm and 0.13 ± 0.07 mm with US and indirect ophthalmoscopy, respectively. In pseudophakic eyes, it was 0.12 ± 0.05 mm and 0.14 ± 0.05 mm with US and indirect ophthalmoscopy, respectively. US and indirect ophthalmoscopy measurements were not statistically different (Student's t-test, P = 1.71). The analysis of the variance among phakic and pseudophakic patients confirmed that measurements of the two groups do not differ significantly (Fisher's exact test, P = 0.16). The univariate analysis showed no significant difference in both US and indirect ophthalmoscopy measurements (ANOVA, P = 0.09) and between the two types of measurements and patient groups (ANOVA, P = 0.38). CONCLUSION: This study suggests relevant accuracy and reliability of US readings and provides the possibility of using this technique for localizing tears in eyes with media opacities by identifying the meridian and corneoscleral limbus-retinal break distance.

Long-Term Surgical Outcomes of Scleral Flap versus Scleral Pocket Technique for Sutureless Intrascleral One-Piece Lens Fixation.

Objectives: This study compared long-term surgical outcomes of the scleral flap versus scleral pocket technique for sutureless intrascleral one-piece intraocular lens (IOL) fixation. Methods: A retrospective comparative study was conducted at a single center, involving consecutive patients undergoing sutureless intrascleral one-piece IOL implantation, between January 2020 and May 2022. Eyes were divided into two groups based on the surgical technique: group 1 underwent scleral flap (n = 64), and group 2 received scleral pocket technique (n = 59). Visual acuity, refractive outcomes, and complications were assessed over a minimum 24-month follow-up period. Results: Both groups showed improvements in best-corrected visual acuity (BCVA), increasing from 0.84 ± 0.56 logMAR at baseline to 0.39 ± 0.23 logMAR (p = 0.042) at 24 months in group 1 and from 0.91 ± 0.63 logMAR at baseline to 0.45 ± 0.38 logMAR (p = 0.039) at 24 months in group 2. No significant differences in BCVA were observed between the groups at baseline (p = 0.991), 12 (p = 0.496) and 24 months (p = 0.557). Mean spherical equivalent (-0.73 ± 1.32 D in group 1 and -0.92 ± 0.99 D in group 2, p = 0.447), refractive prediction error (-0.21 ± 1.1 D in group 1 and -0.35 ± 1.8 D in group 2, p = 0.377), and surgically induced astigmatism (0.74 ± 0.89 D in group 1 and 0.85 ± 0.76 in group 2, p = 0.651) were comparable between the two groups. An IOL tilt of 5.5 ± 1.8 and 5.8 ± 2.0 degrees (p = 0.867) and an IOL decentration of 0.41 ± 0.21 mm and 0.29 ± 0.11 mm (p = 0.955) were obtained, respectively, in group 1 and group 2 at 24 months. Mean endothelial cell density remained stable at 24 months in both groups (p = 0.832 in group 1 and p = 0.443 in group 2), and it was 1747.20 ± 588.03 cells/mm2 in group 1 and 1883.71 ± 621.29 cells/mm2 in group 2 (p = 0.327) at baseline, 1545.36 ± 442.3 cells/mm2 in group 1 and 1417.44 ± 623.40 cells/mm2 in group 2 (p = 0.483) at 24 months. No cases of endophthalmitis were observed. Conclusions: The scleral pocket technique for sutureless intrascleral one-piece IOL fixation is comparable to the traditional scleral flap technique in terms of long-term visual outcomes and safety. The scleral pocket technique offers a simplified approach and a viable option even for less experienced surgeons.

Efficacy and safety of UT-DSAEK combined with Carlevale's sutureless scleral fixation IOL.

PURPOSE: To evaluate a novel surgical combination of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) and sutureless scleral fixation for Carlevale intraocular lens (SSF-Carlevale IOL) implantation to manage corneal endothelial decompensation when there is a concomitant need for secondary IOL fixation. METHODS: Clinical data collected from 10 eyes of 9 patients with bullous keratopathy (BK) who underwent combined UT-DSAEK and SSF-Carlevale IOL implantation in a single procedure were retrospectively analyzed. Anterior chamber IOL (4 cases), aphakia (4 cases, 1 of which associated with PEX), and previous trauma (2 cases) were the conditions responsible for BK. Corrected distance visual acuity (CDVA), intraocular pressure (IOP), endothelial cell density (ECD), central corneal thickness (CCT), graft thickness (GT) and complications were recorded over a 12-month follow-up period. RESULTS: In 90% (9/10) of eyes graft clarity was maintained during follow-up. The mean CDVA improved significantly (p < 0.0001) from 1.78 ± 0.76 logMAR preoperatively to 0.53 ± 0.3 logMAR at 12 months. ECD on average decreased from 2575 ± 125.3 cells/mm2 (donor tissue) to 1697 ± 133.3 cells/mm2 in 12 months. The mean CCT decreased from 870 ± 200 µm to 650 µm ± 9 at 12 months (ANOVA, p = 0.0005). CONCLUSIONS: Combined UT-DSAEK and SSF-Carlevale IOL implantation was associated with good corneal graft survival and IOP control, with few complications. These findings suggest that this surgical approach is a practical option for patients requiring both treatment for corneal endothelial dysfunction and secondary IOL implantation.

[Gastric atresia, diaphragmatic hernia, and gastroesophageal reflux: a rare malformation requiring a multiple approach]. / Atresia del corpo gastrico, ernia diaframmatica laterale sinistra, reflusso gastro-esofageo. Malformazione rara e complessa trattata in più stadi con tecnica mista.

The first cases of atresia or web in the pyloric and prepyloric regions were described in the literature since 1937. To date, only one case of atresia at the junction between the fundus and the body of the stomach has been reported. We want to describe a complex case with incomplete atresia between fundus and gastric body, with left lateral diaphragmatic hernia, treated in several stages by endoscopic, open surgery and minimally invasive surgery

Determination of the anal position in newborns and in children with chronic constipation: comparative study in two European healthcare centres.

INTRODUCTION: The objective of this study was to determine the normal anal position index (API) in neonates and in a group of older children with chronic constipation, and to identify the incidence of anterior ectopic anus (AEA) in the two groups. MATERIALS AND METHODS: A prospective random study was carried out in two European hospitals determining the API in 1,012 neonates (529 in Group A, and 483 in Group B) and in 64 children suffering chronic constipation of ages between 3 months and 12 years (Group C). The API is defined as the ratio between the fourchette-anal and fourchette-coccygeal distances in girls and the scroto-anal and scroto-coccygeal distances in boys. The gestational age, weight, meconium evacuation and anal calibre were recorded in Groups A and B, and age, sex, and API in Group C. Statistical comparisons were made using Student's t test and Welch's t test for independent sample groups. RESULTS: The mean API in Group A was 0.53 ± 0.06 in males and 0.40 ± 0.05 in females, and in Group B 0.51 ± 0.06 in males and 0.39 ± 0.08 in females, with significant differences between the sexes (p < 0.0001) in both groups; 1.7% of the neonates in Group A and 2.4% of Group B presented AEA. 4/13 newborns females with AEA presented with severe constipation during their first months of life. For the 64 patients in Group C: 59.3% were female; the mean API was 0.47 ± 0.1 in males and 0.36 ± 0.1 in females (p < 0.0001). The incidence of AEA was 47% in females and 35% in males. CONCLUSIONS: In the neonates (Groups A and B), the position of the anus in the perineum was more anterior in females than in males (p < 0.0001); 31% of the newborns females with AEA presented with constipation in their first months of life. In the Group C patients, there was a high incidence of AEA, especially in the females, and we consider it to be the probable cause of this defecation disorder.

Anorectal malformations (ARM): quality of life assessed in the functional, urologic and neurologic short and long term follow-up.

UNLABELLED: Imperforate anus represents a wide spectrum of anorectal malformations associated with urologic, neurologic and orthopedic malformations. The outcome from the various corrective measures has improved due to new surgical techniques as well as to a better understanding of the pathology. Other factors which influence the overall outcome include the degree of patient acceptance, family support as well as the ability of the health care structure to support the patient's needs on a clinical, functional and psychologic level. AIM OF THE STUDY: Assess (with the new techniques available) the quality of life in the adult patient with ARM and compare it to that experienced by a younger patient; also we wish to determine the correlation between the observed abnormalities with the functional, neurologic and urologic outcome. MATERIALS & METHODS: Sixty-six patients were subjected to PSARP (36 M; 30 F). Six presented with cloaca and 60 with ARM (23 high and 37 low). All patients underwent the same workup to include L/S MRI diagnostics, evaluation for incontinence (urinary and bowel), a urology screening, and if required, a subsequent urodynamic study with rehabilitation and/or bowel management. All answered questionnaires (AIMAR: Italian parent's association of ARM) in order to assess their satisfaction with the current health condition, with the information received and with the treatment and follow-up sessions. The patients were classified into one of two groups. Group A, totaled 33 patients (4 cloacae) with an age range between 2 and 12 years who were operated after 1995. The second, group B, was made up of 33 patients who had been surgically treated before 1995 (age range 15-41 years), had followed the study protocol and had also a neuropsychiatry consult. RESULTS: Overall fecal continence was 69% and of this number 37% were clean without constipation. Twe2nty-one patients (32%) suffered from some form of constipation. Constipation was the most common functional disorder observed in patients who have undergone PSARP. The highest incidence of constipation was found in the ARM (low type), a favorable prognostic group with 43% constipation. Patient with "high" defects and a cloaca had a lower incidence of constipation (18%). Of the 59 patients evaluated, 85% were urinary continent and 15% were incontinent. All of the incontinent patients were in the unfavorable prognostic group of malformations. Urodynamic studies showed 7 neurogenic bladders (NB) and 2 patients with a neurovescical dysfunction (NVD). Of the 50 "dry" patients. 20 had voiding disturbances due to a voiding dysfunction, in the absence of neurologic abnormalities, and presented occasional daytime or nighttime wetting. There was no correlation between the level of the anatomic defect and the urodynamic patterns in the group. Abnormal MRI findings were observed in thirty out of fifty-two patients evaluated. The MRI findings were classified as follows. Severe abnormalities: 7 patients (13%) presented with a combination of skeletal (sacral/lumbar) and spinal cord anomalies. Only spinal cord abnormalities: 12 patients (21%). Only skeletal abnormalities: 11 (19%) patients. Patients were divided into high, low and cloacal malformations. A high degree of statistical correlation was noted between the patients belonging to the cloacae and high defect groups and the abnormal MRI findings. No significant correlation was found between the low defect group and dysrafism, abnormal MRI results and the severity of the malformation. The incidence of Tethered Cord (TC) in our limited number of patients was limited in our study (9% in the high and 7% in the low defect group) when compared to the current literature. Furthermore there was no statistically conclusive evidence that TC by itself affects the urinary or fecal control in our patients. Our recommendation is nevertheless to obtain an MRI study in all patients with ARM. CONCLUSION: All patients 17 and older reported a "good quality of life". Four are married, two with children. Aclose working relationship with the medical personnel is not only necessary but is also well received by the family particularly when younger patients are involved. The adult patient easily adapts even when information is initially scarce. He quickly reaches autonomy with personalized solutions but prefers a longer follow-up time during which, specialized medical facilities will play an important role in the treatment of ARM. Our findings illustrate the importance of both global disease-specific functioning and perceived psychosocial competencies for enhancing the QL of these patients.

Pediatric Use of Recombinant Human Nerve Growth Factor 20 µg/mL Eye Drops (Cenegermin) for Bilateral Neurotrophic Keratopathy in Congenital Corneal Anesthesia.

PURPOSE: This study aimed to present the efficacy and safety of cenegermin eye drop (Oxervate; Dompè Farmaceutici, Milan, Italy) treatment in a pediatric patient affected by neurotrophic keratopathy (NK) with Goldenhar syndrome. METHODS: This case reports an infant presenting ulceration and a small central opacity in the cornea of the right and left eyes, respectively. The NK bilaterally worsened despite the use of therapeutic contact lenses and temporary partial tarsorrhaphy. Magnetic resonance imaging showed absence and hypoplasia of the right and left trigeminal nerves, respectively. Cenegermin eye drops were administered 1 drop/each eye, 6 times daily for 8 weeks to promote corneal healing. RESULTS: Complete healing was achieved in both eyes after treatment. During the 16-month follow-up period, no epithelial defect, recurrence, or complications were noticed, whereas corneal opacities progressively became clearer, although insignificant improvements in corneal sensitivity or in the reflex tearing were observed. CONCLUSIONS: Cenegermin was effective in treating NK in an infant with Goldenhar syndrome.

Long-term Outcomes and Complications of the New Carlevale Sutureless Scleral Fixation Posterior Chamber IOL.

PURPOSE: To evaluate the visual outcomes and possible complications of a new foldable sutureless scleral fixation intraocular lens (SSF-IOL), the Carlevale IOL (Soleko). METHODS: The SSF-IOL, which has two T-shaped self-blocking plugs on each haptic, was inserted into the posterior chamber. Both haptics was grabbed through two sclerotomies and the two short arms were blocked under the scleral flap, without any suture. A complete clinical evaluation was done preoperatively and at 3, 6, and 12 months postoperatively. RESULTS: A total of 54 eyes of 50 consecutive patients were retrospectively analyzed. The mean corrected distance visual acuity was 0.93 ± 0.61 logMAR preoperatively and improved to 0.42 ± 0.34 logMAR at 3 months, 0.42 ± 0.37 logMAR at 6 months, and 0.38 ± 0.38 logMAR at 12 months postoperatively (all P < .0001). The mean corneal endothelial cell density decreased from 1,725.37 ± 528.06 to 1,612.81 ± 522.91 cells/mm2 at 12 months postoperatively (P < .0001). The mean IOL tilt value was 3.1 ± 1.1° at 12 months postoperatively. The authors observed 6 cases (11.1%) of intraoperative rupture of the IOL haptics, 4 cases (7.4%) of early hyphema, 4 cases (7.4%) of macular cystoid edema, 2 cases (3.7%) of haptic exposure under the conjunctiva, and 1 (1.8%) late retinal detachment. CONCLUSIONS: This newly introduced surgical technique provided promising results regarding efficacy and safety. Complications occurred in a few cases and were successfully managed. The Carlevale IOL seems to be a surgical solution combining the advantages of an easy and minimally invasive implantation with a good functional recovery with minimal complications. [J Refract Surg. 2021;37(2):126-132.].

Accuracy of IOL Power Calculation Using the New Carlevale Sutureless Scleral Fixation Posterior Chamber IOL.

PURPOSE: To evaluate the refractive outcomes of the new Carlevale foldable sutureless scleral fixation intraocular lens (SSF-IOL) (Soleko in eyes without capsular support. METHODS: This retrospective, single-center, noncomparative interventional case series included 25 consecutive eyes of 25 consecutive patients with either aphakia or lens/IOL dislocation due to capsular or zonular defects. The Hoffer Q, Holladay 1, and SRK/T formulas, which do not need measurements of the anterior chamber depth to predict the IOL position, were used to calculate the IOL power. Constant optimization was performed to zero out the mean prediction error (PE). The main outcome measures were mean PE ± standard deviation, median absolute error (MedAE), mean absolute error (MAE), and percentage of eyes with a PE within ±0.50 and ±1.00 diopters (D). RESULTS: Mean axial length was 24.09 ± 2.09 mm (range: 21.85 to 32.17 mm). No statistically significant differences were found among the three formulas for any parameter. The PE was zero due to constant optimization and its standard deviation ranged between 0.89 and 0.95 D. The MedAE ranged between 0.30 and 0.34 D, whereas the MAE ranged between 0.62 and 0.67 D. The percentage of eyes with a PE within ±0.50 D was between 56% and 64% and the percentage of eyes with a PE within ±1.00 D was between 69% and 72%. CONCLUSIONS: Reasonably good refractive outcomes can be obtained when implanting SSF-IOLs in eyes with no capsular support, although the accuracy is lower than what is reported for normal in-the-bag IOL implantation. [J Refract Surg. 2021;37(7):472-476.].

Minding the gap between cortisol levels measured with second-generation assays and current diagnostic thresholds for the diagnosis of adrenal insufficiency: a single-center experience.

PURPOSE: The current cut-offs for the diagnosis of adrenal insufficiency (AI) have been established using outdated immunoassays. We compared the cortisol concentrations measured with Roche Cortisol I (R1), the newly available Roche Cortisol II (R2), and liquid chromatography tandem mass spectrometry (LC-MS/MS), the gold standard procedure to measure steroids in patients undergoing the corticotropin (ACTH) test. METHODS: We enrolled 30 patients (age 47 ± 21 years) referred to undergo the ACTH test (1 or 250 µg). Cortisol was measured at 0, 30, and 60 min after stimulation with R1, R2, and LC-MS/MS. AI was diagnosed for R1-stimulated peak cortisol concentrations < 500 nmol/L. RESULTS: Mean cortisol concentrations measured with R2 and LC-MS/MS were comparable, while mean cortisol concentrations measured by R1 were higher than those of both R2 and LC-MS/MS (respectively, basal 411 ± 177, 287 ± 119, and 295 ± 119 nmol/L; at 30 min, 704 ± 204, 480 ± 132, and 500 ± 132 nmol/L; at 60 min, 737 ± 301, 502 ± 196, and 519 ± 201 nmol/L, p ≤ 0.01 for R1 vs. both R2 and LC-MS/MS at each point). Considering the 500 nmol/L cortisol peak cut-off, AI was diagnosed in 5/30 patients using R1 and in 12/30 using R2 (+ 140%). Based on the correlation between R1 and R2, the threshold of 500 nmol/L became 351 nmol/L (12.7 µg/dL) when cortisol was measured with R2, and 368 nmol/L (13.3 µg/dL) with LC-MS/MS. CONCLUSIONS: The use of more specific cortisol assays results in lower cortisol concentrations. This could lead to misdiagnosis and overtreatment when assessing AI with the ACTH test if a different cut-off for cortisol peak is not adopted.

Relugolix for the treatment of uterine fibroids.

INTRODUCTION: Uterine fibroids (UF) are benign tumors common in premenopausal women, with strong impact on the health-care systems. For many years, surgery represented the only therapy for symptomatic fibroids. However, clinicians are observing a switch from surgery to noninvasive methods; in particular, medical treatment has been shown to be efficacious in obtaining a bleeding reduction and in ameliorating patient conditions. AREAS COVERED: The authors review the current options available for the treatment of women with UF, with a special focus on the newest one, relugolix. It is an orally active non-peptide Gonadotropin-releasing hormone (GnRH)-receptor antagonist recently licensed for women with symptomatic fibroids. Relugolix is a well-tolerated safe drug; it is effective in inducing a dose-dependent decrease in menstrual blood loss, with faster reduction of heavy menstrual bleeding (HMB) and a greater shrinkage in fibroid volume compared to the current standard of GnRH agonist treatment. EXPERT OPINION: Relugolix is a promising drug for the non-surgical treatment of women with UF. To date, the only published data come from a well-selected Japanese female population study while results from worldwide ongoing studies are ongoing in order to confirm the efficacy of this GnRH agonist receptor.

Towards an accurate description of the electronic properties of the biphenylthiol/gold interface: the role of exact exchange.

We investigate the role of the exact exchange in describing the biphenylthiol/gold interface. The study is performed by simulating the electronic properties of mercaptobiphenylthiol and aminobiphenylthiol molecules adsorbed on a Au(23) cluster, using local, semilocal and hybrid functionals and an effective exact exchange method, namely, the localized Hartree-Fock (LHF). We find that the local/semilocal functionals strongly underestimate the charge transfer and the bond dipole at the interface due to the self-interaction-error (SIE), which alters the correct level alignment. On the other hand the LHF method is SIE free and predicts a larger charge transfer and bond dipole. We also found that LHF results can be reproduced using hybrid functionals and that conventional local/semilocal correlation functionals are unable to improve over the exchange-only description.

Oral azithromycin and oral doxycycline for the treatment of Meibomian gland dysfunction: A 9-month comparative case series.

Purpose: To compare the efficacy and safety profile of oral azithromycin with that of doxycycline over 9 months in patients experiencing failure with conservative and topical treatment for Meibomian gland dysfunction (MGD), to assess recurrence of MGD, and to determine the number of treatments required. Methods: This is a randomized controlled trial with a cross-over design at a tertiary care center. In all, 115 consecutive patients underwent a complete ophthalmological examination before being randomly assigned to oral treatment with doxycline (4 g for 30 days) or azithromycin (1.25 g for 5 days). Patients were evaluated at 3, 6, and 9 months. Therapy was switched or conservative management maintained according to signs and symptoms. Results: In the azithromycin group, 83.25% of the patients were stable after one treatment, 16.5% needed a further one or two treatments (some had previously been switched to doxycycline), and 5.77% did not improve despite treatment. In the doxycycline group, 33.79% of patients were stable after one treatment, 66.21% needed a further one or two treatments (some had previously switched to azithromycin), and 29.41% did not improve despite treatment (P < 0.05). Minimal gastrointestinal adverse effects (nausea, diarrhea, abdominal cramp, and decreased appetite) were reported, mostly unchanged at the follow-up visits. At the first visit, more adverse effects were reported in the doxycycline group (14/51, 24%) than in the azithromycin group (3/52, 6%; P < 0.005). Conclusion: Both antibiotics were effective and safe for treating patients with persistent MGD, although azithromycin was superior when the reduced dose and the shorter course of therapy (5 days vs. 4 weeks) were taken into consideration. Given the chronic nature of the disease and the improvement in some signs with minimal adverse effects, a shorter therapy seems a safer and more logical alternative to longer regimens.

Mutant p53: an oncogenic transcription factor.

Inactivation of tumor-suppressor genes is one of the key hallmarks of a tumor. Unlike other tumor-suppressor genes, p53 is inactivated by missense mutations in half of all human cancers. It has become increasingly clear that the resulting mutant p53 proteins do not represent only the mere loss of wild-type p53 tumor suppressor activity, but gain new oncogenic properties favoring the insurgence, the maintenance, the spreading and the chemoresistance of malignant tumors. The actual challenge is the fine deciphering of the molecular mechanisms underlying the gain of function of mutant p53 proteins. In this review, we will focus mainly on the transcriptional activity of mutant p53 proteins as one of the potential molecular mechanisms. To date, the related knowledge is still quite scarce and many of the raised questions of this review are yet unanswered.

Sox2 is not required for melanomagenesis, melanoma growth and melanoma metastasis in vivo.

Melanoma is a dangerous form of skin cancer derived from the malignant transformation of melanocytes. The transcription factor SOX2 is not expressed in melanocytes, however, it has been shown to be differentially expressed between benign nevi and malignant melanomas and to be essential for melanoma stem cell maintenance and expansion in vitro and in xenograft models. By using a mouse model in which BRafV600E mutation cooperates with Pten loss to induce the development of metastatic melanoma, we investigated if Sox2 is required during the process of melanomagenesis, melanoma growth and metastasis and in the acquisition of resistance to BRAF inhibitors (BRAFi) treatments. We found that deletion of Sox2 specifically in Pten null and BRafV600E-expressing melanocytes did not prevent tumor formation and did not modify the temporal kinetics of melanoma occurrence compared to Sox2 wt mice. In addition, tumor growth was similar between Sox2 wt and Sox2 deleted (del) melanomas. By querying publicly available databases, we did not find statistically significant differences in SOX2 expression levels between benign nevi and melanomas, and analysis on two melanoma patient cohorts confirmed that Sox2 levels did not significantly change between primary and metastatic melanomas. Melanoma cell lines derived from both Sox2 genotypes showed a similar sensitivity to vemurafenib treatment and the same ability to develop vemurafenib resistance in long-term cultures. Development of vemurafenib resistance was not dependent on SOX2 expression also in human melanoma cell lines in vitro. Our findings exclude an oncogenic function for Sox2 during melanoma development and do not support a role for this transcription factor in the acquisition of resistance to BRAFi treatments.

Sudden cochlear hearing loss as presenting symptom of arachnoid cyst of the posterior fossa.

Arachnoid cysts account for almost 1% of neoformations located in the cerebellopontine angle. The aetiopathogenesis is unknown. Arachnoid cysts of the cranial posterior fossa may produce symptoms typical of a tumour such as headache, dizziness, tinnitus and progressive sensorineural hearing loss. Management of these lesions is still controversial; if the arachnoid cyst is symptomatic, surgical treatment is usually recommended. The case is described of an adult female with sudden unilateral cochlear hearing loss as presenting symptom of an arachnoid cyst in the cranial posterior fossa.

Visible quantum plasmonics from metallic nanodimers.

We report theoretical evidence that bulk nonlinear materials weakly interacting with highly localized plasmonic modes in ultra-sub-wavelength metallic nanostructures can lead to nonlinear effects at the single plasmon level in the visible range. In particular, the two-plasmon interaction energy in such systems is numerically estimated to be comparable with the typical plasmon linewidths. Localized surface plasmons are thus predicted to exhibit a purely nonclassical behavior, which can be clearly identified by a sub-Poissonian second-order correlation in the signal scattered from the quantized plasmonic field under coherent electromagnetic excitation. We explicitly show that systems sensitive to single-plasmon scattering can be experimentally realized by combining electromagnetic confinement in the interstitial region of gold nanodimers with local infiltration or deposition of ordinary nonlinear materials. We also propose configurations that could allow to realistically detect such an effect with state-of-the-art technology, overcoming the limitations imposed by the short plasmonic lifetime.

Reactivation of mutant p53 by a dietary-related compound phenethyl isothiocyanate inhibits tumor growth.

Mutations in the p53 tumor-suppressor gene are prevalent in human cancers. The majority of p53 mutations are missense, which can be classified into contact mutations (that directly disrupts the DNA-binding activity of p53) and structural mutations (that disrupts the conformation of p53). Both of the mutations can disable the normal wild-type (WT) p53 activities. Nevertheless, it has been amply documented that small molecules can rescue activity from mutant p53 by restoring WT tumor-suppressive functions. These compounds hold promise for cancer therapy and have now entered clinical trials. In this study, we show that cruciferous-vegetable-derived phenethyl isothiocyanate (PEITC) can reactivate p53 mutant under in vitro and in vivo conditions, revealing a new mechanism of action for a dietary-related compound. PEITC exhibits growth-inhibitory activity in cells expressing p53 mutants with preferential activity toward p53(R175), one of the most frequent 'hotspot' mutations within the p53 sequence. Mechanistic studies revealed that PEITC induces apoptosis in a p53(R175) mutant-dependent manner by restoring p53 WT conformation and transactivation functions. Accordingly, in PEITC-treated cells the reactivated p53(R175) mutant induces apoptosis by activating canonical WT p53 targets, inducing a delay in S and G2/M phase, and by phosphorylating ATM/CHK2. Interestingly, the growth-inhibitory effects of PEITC depend on the redox state of the cell. Further, PEITC treatments render the p53(R175) mutant sensitive to degradation by the proteasome and autophagy in a concentration-dependent manner. PEITC-induced reactivation of p53(R175) and its subsequent sensitivity to the degradation pathways likely contribute to its anticancer activities. We further show that dietary supplementation of PEITC is able to reactivate WT activity in vivo as well, inhibiting tumor growth in xenograft mouse model. These findings provide the first example of mutant p53 reactivation by a dietary compound and have important implications for cancer prevention and therapy.

Scanning electron microscopy of cochlea in new-born rats exposed to hyperbaric oxygen: preliminary report.

The aetiology of hearing loss in new-borns in neonatal intensive care is still debated. While the physiopathology of brain, lung and retina damage related to oxygen supplementation has been widely described, no studies have been carried out to define the relationship between hearing loss and supplementation of oxygen in new-borns. In the present investigation, the cochlear morphology of new-born rats was evaluated by means of scanning electron microscopy in order to assess morphological changes after supplemental oxygen administration. After treatment, electron microscopy revealed many changes in the morphology of outer hair cells, if compared to normal rats of the same age. The results suggest that cochlear changes are similar to those previously observed in other regions and may be related to a vascular mechanism of hypoxia-ischaemia and neovascularization and/or an oxidative stress.