We propose the use of weakly nonlinear passive materials for prospective applications in integrated quantum photonics. It is shown that strong enhancement of native optical nonlinearities by ...electromagnetic field confinement in photonic crystal resonators can lead to single-photon generation only exploiting the quantum interference of two coupled modes and the effect of photon blockade under resonant coherent driving. For realistic system parameters in state of the art microcavities, the efficiency of such a single-photon source is theoretically characterized by means of the second-order correlation function at zero-time delay as the main figure of merit, where major sources of loss and decoherence are taken into account within a standard master equation treatment. These results could stimulate the realization of integrated quantum photonic devices based on non-resonant material media, fully integrable with current semiconductor technology and matching the relevant telecom band operational wavelengths, as an alternative to single-photon nonlinear devices based on cavity quantum electrodynamics with artificial atoms or single atomic-like emitters.
Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF). The mechanism of the ...formation of the aggregates in the nucleus remains uncertain. The present study demonstrated that the DNA-binding domain of p53 (p53C) underwent phase separation (PS) on the pathway to aggregation under various conditions. p53C phase separated in the presence of the crowding agent polyethylene glycol (PEG). Similarly, mutant p53C (M237I and R249S) underwent PS; however, the process evolved to a solid-like phase transition faster than that in the case of wild-type p53C. The data obtained by microscopy of live cells indicated that transfection of mutant full-length p53 into the cells tended to result in PS and phase transition (PT) in the nuclear compartments, which are likely the cause of the GoF effects. Fluorescence recovery after photobleaching (FRAP) experiments revealed liquid characteristics of the condensates in the nucleus. Mutant p53 tended to undergo gel- and solid-like phase transitions in the nucleus and in nuclear bodies demonstrated by slow and incomplete recovery of fluorescence after photobleaching. Polyanions, such as heparin and RNA, were able to modulate PS and PT
in vitro
. Heparin apparently stabilized the condensates in a gel-like state, and RNA apparently induced a solid-like state of the protein even in the absence of PEG. Conditions that destabilize p53C into a molten globule conformation also produced liquid droplets in the absence of crowding. The disordered transactivation domain (TAD) modulated both phase separation and amyloid aggregation. In summary, our data provide mechanistic insight into the formation of p53 condensates and conditions that may result in the formation of aggregated structures, such as mutant amyloid oligomers, in cancer. The pathway of mutant p53 from liquid droplets to gel-like and solid-like (amyloid) species may be a suitable target for anticancer therapy.
Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF).
Background
Leaks are considered one of the major complications of laparoscopic sleeve gastrectomy (LSG) with a reported rate up to 7 %. Drainage of the collection coupled with SEMS deployment is the ...most frequent treatment. Its success is variable and burdened by high morbidity and not irrelevant mortality. The aim of this paper is to suggest and establish a new approach by endoscopic internal drainage (EID) for the management of leaks.
Methods
Since March 2013, 67 patients presenting leak following LSG were treated with deployment of double pigtail plastic stents across orifice leak, positioning one end inside the collection and the other end in remnant stomach. The aim of EID is to internally drain the collection and at the same time promote leak healing.
Results
Double pigtails stent were successfully delivered in 66 out of 67 patients (98.5 %). Fifty patients were cured by EID after a mean time of 57.5 days and an average of 3.14 endoscopic sessions. Two died for event not related to EID. Nine are still under treatment; five failure had been registered. Six patients developed late stenosis treated endoscopically.
Conclusions
EID proved to be a valid, curative, and safe mini-invasive approach for treatment of leaks following SG. EID achieves complete drainage of perigastric collections and stimulates mucosal growth over the stent. EID is well tolerated, allows early re-alimentation, and it is burdened by fewer complications than others technique. Long-term follow-up confirms good outcomes with no motility or feeding alterations.
Summary
To assess the impact of socioeconomic status (SES) on the occurrence of skin cancer in the population living in the province of Ferrara, Italy, a retrospective cohort of patients with ...squamous cell carcinoma (SCC), basal cell carcinoma (BCC) or malignant melanoma (MM), provided by the local cancer registry, was investigated. The SES was expressed through an ecological‐based deprivation index. During the 8‐year study period (2006–2013, total person‐years 2 859 137), 6051 carcinomas (1535 SCCs, 4365 BCCs) and 459 MMs were diagnosed. Both crude and standardized (on the European population) rates and the standardized incidence ratio showed a direct correlation between BCC and SES. Multivariate analysis confirmed these results for BCC and also for MM, while it showed an excess of SCC incidence in the lowest SES subgroup. This study shows, for the first time, to our knowledge, opposite effects of SES on SCC and BCC occurrence. A role of environmental factors conditioned by SES may be hypothesized.
Abstract
The aggregation of tropical convection greatly influences the mean‐state of the atmosphere, altering humidity distributions, total atmospheric radiative cooling, and cloud amounts. Although ...studies have demonstrated the sensitivity of convective aggregation to horizontal resolution and domain size, few studies have explored the impact of
vertical
resolution on convective aggregation. Here, we investigate the impact of vertical resolution on simulations of deep convection and convective aggregation using the System for Atmospheric Modeling convection resolving model. We analyze simulations of tropical radiative‐convective equilibrium with varying vertical levels (32, 64, 128, and 256) across small (100 km), medium (700 km) and large (1,500 km) domains. We demonstrate that relative humidity and cloud fraction decrease with increasing vertical resolution as a result of reduced turbulent mixing. Vertical resolution also influences the occurrence of, onset time, and equilibrium intensity of aggregated convection, and also appears to affect the sensitivity of convective aggregation to domain size. Understanding how simulated convection aggregates, as well as its simulated sensitivity to model formulation, is critical for making and interpreting future predictions of global climate change.
Plain Language Summary
We study the simulation of clouds and storms in simple computer models of the tropical atmosphere. These models calculate air movement on a grid. Large grid boxes result in a very coarse, pixelated representation of the atmosphere, while smaller grid boxes offer a much clearer, high‐resolution video. Ideally, the average air movement, cloud formation, and rainfall simulated by these models shouldn't be affected by the size of the grid boxes, with smaller boxes just providing additional detail. However, here we show that the height of grid boxes influences average properties of the simulations, such as the total cloud amount, the amount of rain that falls, and the relative humidity.
Key Points
The relative humidity and high cloud fraction both decrease with increasing vertical resolution in System for Atmospheric Modeling
Vertical resolution impacts convective aggregation occurrence, onset time, and equilibrium intensity
The sensitivity of convective aggregation to domain size may depend on vertical resolution
p53 is a tumor suppressor protein that is mutated in more than 50% of cancer cases. When mutated, it frequently results in p53 oncogenic gain of function (GOF), resulting in a greater tendency to ...aggregate in the phase separation and phase transition pathway. GOFs related to p53 aggregation include chemoresistance, which makes therapy even more difficult. The therapies available for the treatment of cancer are still quite limited, so the study of new molecules and therapeutic targets focusing on p53 aggregates is a promising strategy against cancer. In this review, we classify anticancer molecules with antiaggregation properties into four categories: thiol alkylating agents, designed peptides, agents with chaperone-based mechanisms that inhibit p53 aggregation, and miscellaneous compounds with anti-protein aggregation properties that have been studied in neurodegenerative diseases. Furthermore, we highlight autophagy as a possible degradation pathway for aggregated p53. Here, considering cancer as a protein aggregation disease, we review strategies that have been used to disrupt p53 aggregates, leading to cancer regression.
In Italy, some of the highest incidence rates (IRs) of thyroid cancer (TC) worldwide have been reported.
TC cases <85 years of age reported to Italian cancer registries during 1991–2005 were ...included. Age-standardized IRs were computed for all TC and age–period–cohort effects were estimated for papillary TC.
IRs of TC were twofold higher in 2001–2005 than in 1991–1995 (18 and 8 per 100000 women, 6 and 3 per 100000 men, respectively). Increases were similar in the two sexes and nearly exclusively due to papillary TC. Increases of papillary TC by birth cohort were found in both sexes and among all age groups between 20 and 79 years. Age–period–cohort models showed a strong period effect in both sexes (rate ratio for 2001–2009 versus 1991–1995 = 2.5 in women and 2.3 in men), although IRs peaked at an earlier age in women (45–49 years) than men (65–69 years).
The strength of the period effect in both sexes and the earlier onset in women than men strongly implicated increased medical surveillance in the upward trends of papillary TC incidence in Italy. The consequences of the current intense search for TC on morbidity and possible overtreatment, especially among young women, should be carefully evaluated.
Introduction
On March 13th 2020, in execution of the Law Decree 14/2020 regarding the reorganization of National Health Care related to COVID-19 emergency, all non-urgent outpatient healthcare ...services were suspended in Italy. The present work describes remote support and online group psychotherapy set in motion during COVID-19 emergency for outpatients with Binge Eating Disorder.
Objectives
Aim of the present work is to describe and evaluate online support and group psychotherapy for outpatients with Binge Eating Disorder during lockdown due to COVID-19 emergency. Outcomes were evaluated by remote administration of questionnaires.
Methods
20 outpatients with Binge Eating Disorder, treated by psychotherapists of Hospital Psychology Unit in Psychiatry Day Hospital of an Italian General Hospital, received remote support by phone calls and online group psychotherapy from march to may 2020. During the first two weeks, patients were supported via phone calls. From the third week on, they took part to online group psychotherapy sessions, held every week at the same day and time. Pre-post remote administration of Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) and the Questionnaire of Eating Behaviours (Scheda dei Comportamenti Alimentari, SCA) was used to evaluate outcomes. Data were analyzed by Student’s t-test.
Results
No significant difference was found, thus indicating stability of symptomatology.
Conclusions
Lockdown was a highly stressful period, in which many people lost control on eating behaviours and those with Binge Eating Disorder were expected to have an exacerbation of symptoms. Remote support and online group psychotherapy proved effective in protecting patients from a possible aggravation of their condition.
Urinary incontinence is a common and debilitating problem in patients undergoing radical prostatectomy. Current methods developed to treat urinary incontinence include conservative treatments, such ...as lifestyle education, pelvic muscle floor training, pharmacotherapy, and surgical treatments, such as bulking agents use, artificial urinary sphincter implants, retrourethral transobturator slings, and adjustable male sling system. Pelvic floor muscle exercise is the most common management to improve the strength of striated muscles of the pelvic floor to try to recover the sphincter weakness. Antimuscarinic drugs, phosphodiesterase inhibitors, duloxetine, and a-adrenergic drugs have been proposed as medical treatments for urinary incontinence after radical prostatectomy. Development of new surgical techniques, new surgical tools and materials, such as male slings, has provided an improvement of outcomes after UI surgery. Such improvement is still ongoing, and the uptake of new devices might lead to even better outcomes after UI surgery.
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