Protocell Communication Through the Eyes of Synthetic Organic Chemists

The bottom-up fabrication of synthetic cells (protocells) from molecules and materials, is a major challenge of modern chemistry. A significant breakthrough has been the engineering of protocells capable of chemical communication using bio- derived molecules and ex situ stabilised cell machineries. These, however, suffer from short shelf-lives, high costs, and require mild aqueous conditions. In this Concept Article we analyse the chemistry at the heart of protocell communication to highlight new opportunities for synthetic chemists in protocell engineer- ing. Specifically, we (i) categorise the main bio-derived chemical communication machineries in enzyme cascades, DNA strand displacement, and gene-mediated communication; (ii) review the chemistries of these signal transduction machineries; and (iii) introduce new types of bio-inspired, fully synthetic artificial enzymes to replace their natural counterparts. Developing protocells that incorporate synthetic analogues of bio-derived signal transduction machineries will improve the robustness, stability, and versatility of protocells, and broaden their applications to highly strategic fields such as photocatalysis and fine chemicals production

Treatment of squamous cell carcinoma of the anal canal: A new strategies with anti-EGFR therapy and immunotherapy

The incidence of squamous cell carcinoma of the anal canal (SCAC) is increasing in both sexes but the standard treatment remains that of 20 years ago. However, interesting data have recently emerged on the use of anti-epidermal growth factor receptor (EGFR) agents and immunotherapy in advanced disease. Thus, new avenues of research are opening up that will hopefully lead to more effective therapeutic strategies. We provide an overview of the latest studies published on this tumor and discuss the possible future therapeutic options for combination therapy, anti-EGFR treatment and radiotherapy

Oscillatons revisited

In this paper, we study some interesting properties of a spherically symmetric oscillating soliton star made of a real time-dependent scalar field which is called an oscillaton. The known final configuration of an oscillaton consists of a stationary stage in which the scalar field and the metric coefficients oscillate in time if the scalar potential is quadratic. The differential equations that arise in the simplest approximation, that of coherent scalar oscillations, are presented for a quadratic scalar potential. This allows us to take a closer look at the interesting properties of these oscillating objects. The leading terms of the solutions considering a quartic and a cosh scalar potentials are worked in the so called stationary limit procedure. This procedure reveals the form in which oscillatons and boson stars may be related and useful information about oscillatons is obtained from the known results of boson stars. Oscillatons could compete with boson stars as interesting astrophysical objects, since they would be predicted by scalar field dark matter models.Comment: 10 pages REVTeX, 10 eps figures. Updated files to match version published in Classical and Quantum Gravit

Factorial phase III randomised trial of rofecoxib and prolonged constant infusion of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in NSCLC (GECO) study.

Background. The addition of cyclo-oxygenase-2 (COX-2) inhibitors and prolonged constant infusion (PCI) of gemcitabine to treatment for advanced non-small-cell lung cancer (NSCLC) might improve treatment efficacy. We aimed to assess whether the addition of rofecoxib or PCI gemcitabine could improve overall survival compared with first-line treatment with cisplatin plus gemcitabine given by standard infusion. Methods. Patients with stage IV or IIIb (with supraclavicular nodes or pleural effusion) NSCLC who were under 70 years of age and who had performance status 0 or 1 were eligible for this multicentre, prospective, open-label, randomised phase III trial with 2×2 factorial design. Patients were randomly assigned to one of four treatment groups: group A,gemcitabine 1200 mg/m2 in a 30-min intravenous infusion on days 1 and 8 and intravenous cisplatin 80 mg/m2 on day 1, every 21 days for six cycles; group B, the same treatments as group A plus oral rofecoxib 50 mg/day until disease progression; group C, intravenous PCI gemcitabine 1200 mg/m2 in a 120-min infusion on days 1 and 8 and intravenous cisplatin 80 mg/m2 on day 1, every 21 days for six cycles; group D, the same drugs as group C plus oral rofecoxib 50 mg/day until disease progression. The primary endpoint was overall survival; secondary endpoints were progression free survival, response rate, quality of life, and toxicity. Analyses were intention-to-treat. This trial is registered on the clinical trials site of the US National Institutes of Health website http://clinicaltrials.gov/ct/show/NCT00385606. Findings. Between Jan 30, 2003, and May 3, 2005, 400 patients were enrolled. Median age was 60 years (range 29–71). PCI gemcitabine did not improve overall survival (median 47 weeks [95% CI 40–55] vs 44 [36–52], with standard gemcitabine infusion, hazard ratio (HR) of death 0·93 [0·74–1·17], p=0·41), progression-free survival, nor any other secondary endpoint. Vomiting and fatigue were significantly worse with PCI gemcitabine. The two rofecoxib groups were closed early (on Oct 1, 2004) due to withdrawal of the drug because of safety issues. With intention-to-treat statistical analyses limited to 240 patients (ie, those randomised before July 1, 2004) who had at least 3 months of treatment, rofecoxib did not prolong overall survival (median 44 weeks [CI 36–55] vs 44 [40–54] without rofecoxib, and HR of death 1·00 [0·75–1·34], p=0·85), or progression-free survival, but did improve response rate (41% vs 26%, p=0·02), global quality of life, physical, emotional and role functioning, fatigue, and sleeping. Rofecoxib significantly increased the incidence of diarrhoea and decreased constipation, fatigue, fever, weight loss, and pain, and analgesic consumption. Severe cardiac ischaemia was more frequent with rofecoxib than without; however, the diff erence was not statistically signifi cant in the primary analysis (p=0·06) and became significant when patients who were randomised between July 1, 2004, and Sept 30, 2004, were included in the analysis (p=0·03). Interpretation. Neither PCI gemcitabine nor rofecoxib prolonged survival in the patients in this study. Rofecoxib improved response rate and several quality-of-life items, including pain-related items and global quality of life. Further studies with less cardiotoxic COX-2 inhibitors are needed in NSCLC

Image-guided multisession radiosurgery of skull base meningiomas

Background: The efficacy of single-session stereotactic radiosurgery (sSRS) for the treatment of intracranial meningioma is widely recognized. However, sSRS is not always feasible in cases of large tumors and those lying close to critically radiation-sensitive structures. When surgery is not recommended, multi-session stereotactic radiosurgery (mSRS) can be applied. Even so, the efficacy and best treatment schedule of mSRS are not yet established. The aim of this study is to validate the role of mSRS in the treatment of skull base meningiomas. Methods: A retrospective analysis of patients with skull base meningiomas treated with mSRS (two to five fractions) at the University of Messina, Italy, from 2008 to 2018, was conducted. Results: 156 patients met the inclusion criteria. The median follow-up period was 36.2 \ub1 29.3 months. Progression-free survival at 2-, 5-, and 10-years was 95%, 90%, and 80.8%, respectively. There were no new visual or motor deficits, nor cranial nerves impairments, excluding trigeminal neuralgia, which was reported by 5.7% of patients. One patient reported carotid occlusion and one developed brain edema. Conclusion: Multisession radiosurgery is an effective approach for skull base meningiomas. The long-term control is comparable to that obtained with conventionally-fractionated radiotherapy, while the toxicity rate is very limited

On the thermal footsteps of Neutralino relic gases

Current literature suggests that neutralinos are the dominant cold dark matter particle species. Assuming the microcanonical definition of entropy, we examine the local entropy per particle produced between the ``freeze out'' era to the present. An ``entropy consistency'' criterion emerges by comparing this entropy with the entropy per particle of actual galactic structures given in terms of dynamical halo variables. We apply this criterion to the cases when neutralinos are mosly b-inos and mostly higgsinos, in conjunction with the usual ``abundance'' criterion requiring that present neutralino relic density complies with 0.1 < \Omega_{\chic{\tilde\chi^0_1}} < 0.3 for $h\simeq 0.65$. The joint application of both criteria reveals that a better fitting occurs for the b-ino channels, hence the latter seem to be favoured over the higgsino channels. The suggested methodology can be applied to test other annihilation channels of the neutralino, as well as other particle candidates of thermal gases relics.Comment: LaTex AIP style, 8 pages including 1 figure. Final version to appear in Proceedings of the Mexican School of Astrophysics (EMA), Guanajuato, M\'exico, July 31 - August 7, 200

ICER is requisite for Th17 differentiation.

Inducible cAMP early repressor (ICER) has been described as a transcriptional repressor isoform of the cAMP response element modulator (CREM). Here we report that ICER is predominantly expressed in Th17 cells through the IL-6-STAT3 pathway and binds to the Il17a promoter, where it facilitates the accumulation of the canonical enhancer RORγt. In vitro differentiation from naive ICER/CREM-deficient CD4(+) T cells to Th17 cells is impaired but can be rescued by forced overexpression of ICER. Consistent with a role of Th17 cells in autoimmune and inflammatory diseases, ICER/CREM-deficient B6.lpr mice are protected from developing autoimmunity. Similarly, both anti-glomerular basement membrane-induced glomerulonephritis and experimental encephalomyelitis are attenuated in ICER/CREM-deficient mice compared with their ICER/CREM-sufficient littermates. Importantly, we find ICER overexpressed in CD4(+) T cells from patients with systemic lupus erythematosus. Collectively, our findings identify a unique role for ICER, which affects both organ-specific and systemic autoimmunity in a Th17-dependent manner

Prevalence and management of pain in Italian patients with advanced non-small-cell lung cancer

Pain is a highly distressing symptom for patients with advanced cancer. WHO analgesic ladder is widely accepted as a guideline for its treatment. Our aim was to describe pain prevalence among patients diagnosed with advanced non-small-cell lung cancer (NSCLC), impact of pain on quality of life (QoL) and adequacy of pain management. Data of 1021 Italian patients enrolled in three randomised trials of chemotherapy for NSCLC were pooled. QoL was assessed by EORTC QLQ-C30 and LC-13. Analgesic consumption during the 3 weeks following QoL assessment was recorded. Adequacy of pain management was evaluated by the Pain Management Index (PMI). Some pain was reported by 74% of patients (42% mild, 24% moderate and 7% severe); 50% stated pain was affecting daily activities (30% a little, 16% quite a bit, 3% very much). Bone metastases strongly affected presence of pain. Mean global QoL linearly decreased from 64.9 to 36.4 from patients without pain to those with severe pain (P<0.001). According to PMI, 616 out of 752 patients reporting pain (82%) received inadequate analgesic treatment. Bone metastases were associated with improved adequacy and worst pain with reduced adequacy at multivariate analysis. In conclusion, pain is common in patients with advanced NSCLC, significantly affects QoL, and is frequently undertreated. We recommend that: (i). pain self-assessment should be part of oncological clinical practice; (ii). pain control should be a primary goal in clinical practice and in clinical trials; (iii). physicians should receive more training in pain management; (iv). analgesic treatment deserves greater attention in protocols of anticancer treatment

Can dark matter be a Bose-Einstein condensate?

We consider the possibility that the dark matter, which is required to explain the dynamics of the neutral hydrogen clouds at large distances from the galactic center, could be in the form of a Bose-Einstein condensate. To study the condensate we use the non-relativistic Gross-Pitaevskii equation. By introducing the Madelung representation of the wave function, we formulate the dynamics of the system in terms of the continuity equation and of the hydrodynamic Euler equations. Hence dark matter can be described as a non-relativistic, Newtonian Bose-Einstein gravitational condensate gas, whose density and pressure are related by a barotropic equation of state. In the case of a condensate with quartic non-linearity, the equation of state is polytropic with index $n=1$. To test the validity of the model we fit the Newtonian tangential velocity equation of the model with a sample of rotation curves of low surface brightness and dwarf galaxies, respectively. We find a very good agreement between the theoretical rotation curves and the observational data for the low surface brightness galaxies. The deflection of photons passing through the dark matter halos is also analyzed, and the bending angle of light is computed. The bending angle obtained for the Bose-Einstein condensate is larger than that predicted by standard general relativistic and dark matter models. Therefore the study of the light deflection by galaxies and the gravitational lensing could discriminate between the Bose-Einstein condensate dark matter model and other dark matter models.Comment: 20 pages, 7 figures, accepted for publication in JCAP, references adde