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.

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.].

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.].

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.

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.

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.

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.

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.

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.

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.

Combined deep sclerectomy and descemet stripping automated endothelial keratoplasty.

PURPOSE: The aim of this study was to evaluate a novel surgical combination of Descemet stripping automated endothelial keratoplasty (DSAEK) and deep sclerectomy (DS) for the management of concomitant corneal endothelial decompensation and uncontrolled glaucoma. METHODS: This retrospective case series noncomparative study included 9 eyes of 6 consecutive patients with coexistence of corneal edema resulting from Fuchs dystrophy or pseudoexfoliation keratopathy and medically uncompensated glaucoma; these patients underwent combined DSAEK and DS with mitomycin C and an absorbable collagen implant. Corneal graft clarity, endothelial cell density, visual acuity, intraocular pressure (IOP), and identification of complications were assessed over a 2-year follow-up. RESULTS: All eyes obtained graft clarity throughout the follow-up, with a final average endothelial cell decrease of -36% from baseline, and showed improved vision and good IOP control without hypotensive therapy. Measured at 3 and 24 months postoperation, the mean visual acuity improvement was 154% and 372% and IOP decrease was 51.1% and 46.4%, respectively. Two anterior segment complications occurred in 2 (22%) patients' eyes. This consisted of a graft dislocation and a modest IOP elevation, treated successfully. CONCLUSIONS: Combined DSAEK and DS was longitudinally associated with good corneal graft survival and IOP control, with few complications. These findings suggest that this surgical approach is a viable option for patients with coexisting glaucoma and corneal endothelial dysfunction. Our study should stimulate a multicenter, randomized, controlled trial of our technique.

Gain-of-function mutant p53 downregulates miR-223 contributing to chemoresistance of cultured tumor cells.

Mutant p53 proteins are expressed at high frequency in human tumors and are associated with poor clinical prognosis and resistance to chemotherapeutic treatments. Here we show that mutant p53 proteins downregulate micro-RNA (miR)-223 expression in breast and colon cancer cell lines. Mutant p53 binds the miR-223 promoter and reduces its transcriptional activity. This requires the transcriptional repressor ZEB-1. We found that miR-223 exogenous expression sensitizes breast and colon cancer cell lines expressing mutant p53 to treatment with DNA-damaging drugs. Among the putative miR-223 targets, we focused on stathmin-1 (STMN-1), an oncoprotein known to confer resistance to chemotherapeutic drugs associated with poor clinical prognosis. Mutant p53 silencing or miR-223 exogenous expression lowers the levels of STMN-1 and knockdown of STMN-1 by small interfering RNA increases cell death of mutant p53-expressing cell lines. On the basis of these findings, we propose that one of the pathways affected by mutant p53 to increase cellular resistance to chemotherapeutic agents involves miR-223 downregulation and the consequent upregulation of STMN-1.

ATM kinase enables the functional axis of YAP, PML and p53 to ameliorate loss of Werner protein-mediated oncogenic senescence.

Werner syndrome (WS) results from dysfunction of the WRN protein, and is associated with premature aging and early death. Here we report that loss of WRN function elicits accumulation of the Yes-associated protein (YAP protein), a major effector of the Hippo tumor suppressor pathway, both experimentally and in WS-derived fibroblasts. YAP upregulation correlates with slower cell proliferation and accelerated senescence, which are partially mediated by the formation of a complex between YAP and the PML protein, whose activity promotes p53 activation. The ATM kinase is necessary for YAP and PML accumulation in WRN-depleted cells. Notably, the depletion of either YAP or PML partially impairs the induction of senescence following WRN loss. Altogether, our findings reveal that loss of WRN activity triggers the activation of an ATM-YAP-PML-p53 axis, thereby accelerating cellular senescence. The latter has features of SASP (senescence-associated secretory phenotype), whose protumorigenic properties are potentiated by YAP, PML and p53 depletion.

Systemic treatment with adipose-derived mesenchymal stem cells ameliorates clinical and pathological features in the amyotrophic lateral sclerosis murine model.

Therapeutic strategies for the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are actually minimally effective on patients' survival and quality of life. Although stem cell therapy has raised great expectations, information on the involved molecular mechanisms is still limited. Here we assessed the efficacy of the systemic administration of adipose-derived mesenchymal stem cells (ASC), a previously untested stem cell population, in superoxide-dismutase 1 (SOD1)-mutant transgenic mice, the animal model of familial ALS. The administration of ASC to SOD1-mutant mice at the clinical onset significantly delayed motor deterioration for 4-6 weeks, as shown by clinical and neurophysiological tests. Neuropathological examination of ASC-treated SOD1-mutant mice at day 100 (i.e. the time of their best motor performance) revealed a higher number of lumbar motorneurons than in phosphate-buffered saline-treated SOD1-mutant mice and a restricted number of undifferentiated green fluorescent protein-labeled ASC in the spinal cord. By examining the spinal cord tissue factors that may prolong neuronal survival, we found a significant up-regulation in levels of glial-derived neurotrophic factor (GDNF) and basic fibroblast growth factor (bFGF) after ASC treatment. Considering that ASC produce bFGF but not GDNF, these findings indicate that ASC may promote neuroprotection either directly and/or by modulating the secretome of local glial cells toward a neuroprotective phenotype. Such neuroprotection resulted in a strong and long-lasting effect on motor performance and encourages the use of ASC in human pathologies, in which current therapies are not able to maintain a satisfying neurological functional status.

miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer.

Micro RNAs (miRs) are small non-coding RNAs aberrantly expressed in human tumors. Here, we aim to identify miRs whose deregulated expression leads to the activation of oncogenic pathways in human gastric cancers (GCs). Thirty nine out of 123 tumoral and matched uninvolved peritumoral gastric specimens from three independent European subsets of patients were analyzed for the expression of 851 human miRs using Agilent Platform. The remaining 84 samples were used to validate miRs differentially expressed between tumoral and matched peritumoral specimens by qPCR. miR-204 falls into a group of eight miRs differentially expressed between tumoral and peritumoral samples. Downregulation of miR-204 has prognostic value and correlates with increased staining of Bcl-2 protein in tumoral specimens. Ectopic expression of miR-204 inhibited colony forming ability, migration and tumor engraftment of GC cells. miR-204 targeted Bcl-2 messenger RNA and increased responsiveness of GC cells to 5-fluorouracil and oxaliplatin treatment. Ectopic expression of Bcl-2 protein counteracted miR-204 pro-apoptotic activity in response to 5-fluorouracil. Altogether, these findings suggest that modulation of aberrant expression of miR-204, which in turn releases oncogenic Bcl-2 protein activity might hold promise for preventive and therapeutic strategies of GC.

In situ cleaning of instruments for the sensitive detection of organics on Mars.

A method is presented for in situ cleaning of spacecraft instruments that analyze planetary soil and rock. We have found that vibrating hardware, used to facilitate powder transport, was also effective at removing contamination. Surfaces can be cleaned below monolayer levels using vibrating surfaces in the presence of mineral powder. Both organic and particulate contamination is efficiently removed. Fine grained regolith from the planetary surface or an organic free reference material may serve as the powder used for cleaning. We present both analytical and experimental results for the contamination transfer fraction and the conditions required to clean the hardware prior to sensitive chemical analysis.

MicroRNA-128-2 targets the transcriptional repressor E2F5 enhancing mutant p53 gain of function.

p53 mutations have profound effects on non-small-cell lung cancer (NSCLC) resistance to chemotherapeutic treatments. Mutant p53 proteins are usually expressed at high levels in tumors, where they exert oncogenic functions. Here we show that p53R175H, a hotspot p53 mutant, induces microRNA (miRNA)-128-2 expression. Mutant p53 binds to the putative promoter of miR128-2 host gene, ARPP21, determining a concomitant induction of ARPP21 mRNA and miR-128-2. miR-128-2 expression in lung cancer cells inhibits apoptosis and confers increased resistance to cisplatin, doxorubicin and 5-fluorouracyl treatments. At the molecular level, miR-128-2 post-transcriptionally targets E2F5 and leads to the abrogation of its repressive activity on p21(waf1) transcription. p21(waf1) protein localizes to the cytoplasmic compartment, where it exerts an anti-apoptotic effect by preventing pro-caspase-3 cleavage. This study emphasizes miRNA-128-2 role as a master regulator in NSCLC chemoresistance.

[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