Final MA Portfolio

MA portfolio, Englis

Plants Extracts Loaded in Nanocarriers: An Emergent Formulating Approach:

Over the millennia, plants have represented for Humankind the main source of food, but also a vast resource to maintain health, for prophylactic properties or to cure human and animal diseases. Presently, between 65 and 80% of populations in developing countries use medicinal plants as therapeutic remedies for their primary healthcare and in Europe and USA there is an increasing demand of botanical products both on the form of food supplements and herbal medicinal products. Botanicals on the market are mainly based on traditional (infusions or decoctions), conventional (using organic solvents) and innovative (supercritical CO2 or subcritical water) extracts but there is an increasing demand of essential oils for aromatherapy. Conversely, the clinical use of many extracts is limited due to the need of repeated administrations or high doses because of low hydrophilicity and intrinsic dissolution rate(s), or physical/ chemical instability. Other limits are low absorption, poor pharmacokinetics and bioavailability, scarce biodistribution, first pass metabolism, trivial penetration and accumulation in the organs of the body. In the case of essential oils, the high volatility and instability are further limitations. Nowadays, the design and production of appropriate drug delivery systems, in particular nanosized ones (between 50 and 300 nm), have already entered into clinical use and can offer an advanced approach to optimized the therapeutic efficacy of extracts and essential oils. A successful drug carrier system should have optimal drug loading and release properties, a long shelf life, and exert a much higher therapeutic efficacy as well as lower side effects. Polymeric nanoparticles and lipid based-nanocarriers including micelles, vesicles, nanocochleates, micro- and nanoemulsions represent successful examples of extract nanoformulations overcoming these limitations. This review reports on some paradigmatic success stories of extract and EO nanoformulations with remarkable advantages over conventional formulations, which include increase of solubility, stability, permeation and bioavailability, sustained delivery. Paradigmatic examples include formulations of extracts from Vitex agnus-castus, Sylibum marianum, Phyllanthus amarus, Ginkgo biloba, Panax notoginseng, Hypericum perforatum and thyme essential oil

The Frequency of Polarized Broad Emission Lines in Type 2 Seyfert Galaxies

We have discovered polarized broad emission lines in five type 2 Seyfert galaxies (NGC 424, NGC 591, NGC 2273, NGC 3081, and NGC 4507), establishing that these objects are type 1 Seyferts obscured by dense circumnuclear material. The galaxies are part of a distance-limited sample of 31 Seyfert 2s, for which spectropolarimetric observations are now complete. Combined with published reports, our results indicate that at least 11 of the galaxies in this sample, or > 35%, possess hidden broad-line regions. This represents the first reliable estimate of the frequency of polarized broad emission lines in type 2 Seyferts, which has important implications for the general applicability of Seyfert unification models.Comment: 13 pages, including 5 figures. Accepted for publication in ApJ Letter

Breast and Axilla Treatment in Ductal Carcinoma In Situ

Ductal carcinoma in situ (DCIS) represents a challenge for the breast unit team, beginning from its difficult radiological detection and continuing with its controversial multimodal treatment and management. With the introduction of the mammographic screening, DCIS has become a common diagnosis. In fact, today DCIS is mostly identified by mammography or magnetic resonance imaging (MRI). The increased prevalence of DCIS diagnosis, in the past, raised the problem of the therapeutic management. In this chapter, the breast and axillary surgery in case of DCIS and the most controversial aspects regarding DCIS management are reviewed based on international guidelines and on the current literature

The Hot and Energetic Universe: The close environments of supermassive black holes

Most of the action in Active Galactic Nuclei (AGN) occurs within a few tens of gravitational radii from the supermassive black hole, where matter in the accretion disk may lose up to almost half of its energy with a copious production of X-rays, emitted via Comptonization of the disk photons by hot electrons in a corona and partly reflected by the accretion disk. Thanks to its large effective area and excellent energy resolution, Athena+ contributions in the understanding of the physics of accretion in AGN will be fundamental - and unique - in many respects. It will allow us to map the disk-corona system - which is crucial to understand the mechanism of energy extraction and the relation of the corona with winds and jets - by studying the time lags between reflected and primary photons. These lags have been recently discovered by XMM-Newton, but only Athena+ will have the sensitivity required to fully exploit this technique. Athena+ will also be able e.g. to determine robustly the spin of the black hole in nearby sources (and to extend these measurements beyond the local Universe), to establish the nature of the soft X-ray components, and to map the circumnuclear matter within the AGN inner parsec with unprecedented details.Comment: Supporting paper for the science theme "The Hot and Energetic Universe" to be implemented by the Athena+ X-ray observatory (http://www.the-athena-x-ray-observatory.eu). 9 pages, 8 figure

A BLR origin for the iron Kα\alpha line in NGC7213

The X-ray spectrum of NGC7213 is known to present no evidence for Compton reflection, a unique result among bright Seyfert 1s. The observed neutral iron K$\alpha$ line, therefore, cannot be associated with a Compton-thick material, like the disc or the torus, but is due to Compton-thin gas, with the Broad Line Region (BLR) as the most likely candidate. To check this hypothesis, a long Chandra HETG observation, together with a quasi-simultaneous optical spectroscopic observation at the ESO NTT EMMI were performed. We found that the iron line is resolved with a FWHM=$2 400^{+1 100}_{-600}$ km/s, in perfect agreement with the value measured for the broad component of the H$\alpha$, $2640^{+110}_{-90}$ km/s. Therefore, NGC7213 is the only Seyfert 1 galaxy whose iron K$\alpha$ line is unambiguously produced in the BLR. We also confirmed the presence of two ionised iron lines and studied them in greater detail than before. The resonant line is the dominant component in the Fe XXV triplet, therefore suggesting an origin in collisionally ionised gas. If this is the case, the blueshift of around 1000 km/s of the two ionised iron lines could be the first measure of the velocity of a starburst wind from its X-ray emission.Comment: 5 pages, 4 figures, accepted for publication in MNRAS Letter

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease