“Biweekly oxaliplatin plus irinotecan and folinic acid-modulated 5- fluorouracil: a phase II study in pretreated patients with metastatic colorectal cancer”

Oxaliplatin (OXA) and irinotecan (IRI) are active drugs for metastatic colorectal cancer, their toxicity profiles are not overlapping, and both drugs have shown at least additivity with folinic acid-modulated 5-fluorouracil (5FU). We carried out this phase II study to assess the activity and toxicity of a biweekly regimen including OXA plus IRI on day 1, and levo-folinic acid (LFA) plus 5FU on day 2 (OXIRIFAFU) in pretreated patients with metastatic colorectal cancer. Forty-one patients, all previously treated with adjuvant and/or palliative 5FU-based chemotherapy (16 of them already exposed to IRI, OXA or both), were enrolled into this trial. On the basis of sensitivity to previous treatment, 19 patients were considered as chemo-resistant and 14 patients as chemo-refractory. OXA 110 mg/m (over 2 h) and IRI 175 mg/m (over 1 h) were delivered on day 1, followed by LFA 250 mg/m (2-h infusion) plus 5FU 800 mg/m as intravenous bolus on day 2. Cycles were repeated every 2 weeks. A total of 348 cycles were delivered, with a median of nine cycles per patient (range, 1-12 cycles per patient). Five complete and 13 partial responses were reported on 40 assessable patients, giving a response rate of 45% [95% confidence interval (CI), 29-62%]; eight of 19 (42%) resistant patients and five of 14 (36%) refractory patients achieved a major response, which was also obtained in four of eight (50%) patients pretreated with IRI and in three of eight (38%) patients pretreated with OXA. Grade 3 or higher neutropenia occurred in 68% of patients, but febrile neutropenia or infections affected only seven (17%) patients. No episodes of grade 3 or higher thrombocytopenia or anemia were recorded. Occurrence of severe non-hematologic toxicities by patients were: diarrhea, 34%; vomiting, 17%; peripheral cumulative neuropathy, 15%; stomatitis, 10%; acute cholinergic syndrome, 7%. Actually delivered dose intensities of all three drugs resulted in about two-thirds of the planned ones. After a follow-up of 39 months, median progression-free survival was 7.5 months. Median overall survival was 14.4 (95% CI, 10.4-18.4) months from the start of OXIRIFAFU and 25.3 (95% CI, 18.1-32.5) months from the diagnosis of metastatic disease. This OXIRIFAFU triplet regimen was highly effective in resistant/refractory colorectal cancer patients. A slight dose reduction of all cytotoxic drugs could be advisable in order to improve the tolerability of this regimen without jeopardizing its activity

Tecnologie alimentari: problemi svolti di operazioni unitarie

Le Operazioni Unitarie (OU) costituiscono gli elementi base del flow-sheet di un processo produttivo. Le OU fondamentali comuni a più processi si basano sugli stessi principi, relativi a fenomeni chimico-fisici e biologici, e quindi su tecnologie simili, anche se naturalmente le apparecchiature, i materiali di costruzione e le condizioni operative devono essere adattate. Questa scomposizione logica, permette di realizzare un qualsiasi processo mediante una sequenza ottimale di OU (Biardi G., ed. Città Studi, 2009), in cui occorre che lo studente acquisisca le medesime conoscenze e competenze. Per tale motivo le OU, vengono impartite in un insegnamento a parte, con un metodo “unitario”, che prescindendo dai specifici processi e prodotti alimentari ne semplifica lo studio e ne permette il controllo, l’ottimizzazione e il dimensionamento nelle realtà aziendali. A tal fine lo studio delle OU, impartito nei corsi di studio di Scienze e Tecnologie Alimentari (L/26 e LM/70) e in altri (di chimica, ingegneria, tecnologie farmaceutiche, etc.), si avvale della modellazione, in particolare di quella matematica, per simulare fenomeni reali e prevederne gli effetti; l’acquisizione pertanto di conoscenze di base di tipo fisico-matematico diventa indispensabile

Artichoke Industrial Waste in Durum Wheat Bread: Effects of Two Different Preparation and Drying Methods of Flours and Evaluation of Quality Parameters during Short Storage

'Violetto di Ramacca' is a local variety of artichoke grown in Sicily (Southern Italy), known for its purple color with green streaks. In this study, the effects of two different preparation and drying methods (method A, fresh sample oven-dried at 40 °C for 48 h then mixed and ground into flour; and B, minced and frozen sample oven-dried at 40 °C for 24 h then blended and ground into flour) for flours from different parts of the artichoke (bracts, stems, and mix), used at different percentages of integration (5, 7.5, and 10%), in combination with re-milled semolina, have been evaluated. The polyphenol contents of the flours produced with the two methods were measured. The results showed significant differences between the methods and samples, with a range from 9.09 mg GAE/g d.m. (bracts 100%, method A) to 2.62 mg/g (mix 100%, method B). The values were then lowered in the flour products with supplements ranging from 0.96 mg GAE/g (bract flour 10%, method A) to 0.11 mg GAE/g (mixed flour 7.5%, method B). As the amounts of polyphenols increased, the antioxidant activity increased, with a range that varied in the pure flour from 8.59 mg trolox eq/g d.m. (bract flour, method A) to 3.83 mg trolox eq/g d.m. (mixed flour, method B). These flours were also analyzed for color, highlighting a clear difference between methods A (greener) and B (browner). The flours thus obtained were used to produce breads, which were evaluated for their physicochemical characteristics during 4 days of storage. The results showed a reduction in volumes and heights, an increase in the percentage of integration of the artichoke flours, a greater quantity of moisture in the integrated breads, and a lower reduction in the structural characteristics during storage compared to the control breads. The TPA was conducted on the breads from T0 to T4, highlighting that, although initially more compact, the integrated breads offered less alteration of the values during storage. The aw ranged from 0.63 (mix flour 5%, method B) to 0.90 (bract flour 5%, method B). The amounts of polyphenols (from 0.57 mg GAE/g in bread with bracts at 10% (method A) to 0.13 mg GAE/g in bread with mix 5% (method B)) and the antioxidant activity (from 0.55 mg trolox eq/g d.m. in bread with bract flour 10% (method A) to 0.14% mg trolox eq/g d.m. in bread with mix flour) were also evaluated, showing a trend similar to the values obtained in the flours. Colorimetric tests highlighted a color more similar to wholemeal bread in the loaves produced with method B. Statistical factor analysis and cluster analysis were conducted for all trials

Mesoscopic models for DNA stretching under force: new results and comparison to experiments

Single molecule experiments on B-DNA stretching have revealed one or two structural transitions, when increasing the external force. They are characterized by a sudden increase of DNA contour length and a decrease of the bending rigidity. It has been proposed that the first transition, at forces of 60--80 pN, is a transition from B to S-DNA, viewed as a stretched duplex DNA, while the second one, at stronger forces, is a strand peeling resulting in single stranded DNAs (ssDNA), similar to thermal denaturation. But due to experimental conditions these two transitions can overlap, for instance for poly(dA-dT). We derive analytical formula using a coupled discrete worm like chain-Ising model. Our model takes into account bending rigidity, discreteness of the chain, linear and non-linear (for ssDNA) bond stretching. In the limit of zero force, this model simplifies into a coupled model already developed by us for studying thermal DNA melting, establishing a connexion with previous fitting parameter values for denaturation profiles. We find that: (i) ssDNA is fitted, using an analytical formula, over a nanoNewton range with only three free parameters, the contour length, the bending modulus and the monomer size; (ii) a surprisingly good fit on this force range is possible only by choosing a monomer size of 0.2 nm, almost 4 times smaller than the ssDNA nucleobase length; (iii) mesoscopic models are not able to fit B to ssDNA (or S to ss) transitions; (iv) an analytical formula for fitting B to S transitions is derived in the strong force approximation and for long DNAs, which is in excellent agreement with exact transfer matrix calculations; (v) this formula fits perfectly well poly(dG-dC) and $\lambda$-DNA force-extension curves with consistent parameter values; (vi) a coherent picture, where S to ssDNA transitions are much more sensitive to base-pair sequence than the B to S one, emerges.Comment: 14 pages, 9 figure

XMM-Newton and Suzaku analysis of the Fe K complex in the Seyfert 1 galaxy Mrk 509

We report on partially overlapping XMM-Newton (~260 ks) and Suzaku (~100 ks) observations of the iron K band in the nearby, bright Seyfert 1 galaxy Mrk 509. The source shows a resolved neutral Fe K line, most probably produced in the outer part of the accretion disc. Moreover, the source shows further emission blue-ward of the 6.4 keV line due to ionized material. This emission is well reproduced by a broad line produced in the accretion disc, while it cannot be easily described by scattering or emission from photo-ionized gas at rest. The summed spectrum of all XMM-Newton observations shows the presence of a narrow absorption line at 7.3 keV produced by highly ionized outflowing material. A spectral variability study of the XMM-Newton data shows an indication for an excess of variability at 6.6-6.7 keV. These variations may be produced in the red wing of the broad ionized line or by variation of a further absorption structure. The Suzaku data indicate that the neutral Fe Kalpha line intensity is consistent with being constant on long timescales (of a few years) and they also confirm as most likely the interpretation of the excess blueshifted emission in terms of a broad ionized Fe line. The average Suzaku spectrum differs from the XMM-Newton one for the disappearance of the 7.3 keV absorption line and around 6.7 keV, where the XMM-Newton data alone suggested variability.Comment: MNRAS in pres

Detection and quantification of mammaglobin in the blood of breast cancer patients: can it be useful as a potential clinical marker? Preliminary results of a GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Mammaglobin is expressed mainly in mammary tissue, overexpressed in breast cancer (BC) and rarely in other tissue. The aim of this study was to assess the sensitivity and specificity of transcript MGB1 detection and to evaluate the role of MGB1 as potential clinical marker for the detection of disseminated cancer cells in the blood of BC patients. PATIENTS AND METHODS: A consecutive series of 23 BC tissues, 36 peripheral blood BC samples and 35 healthy peripheral blood samples was prospectively recruited to investigate MGB1 expression by means of a quantitative Real Time RT-PCR assay. RESULTS: MGB1 overexpression in tissue samples of BC patients is significantly associated only with high level of Ki67 (P <0.05). None of the samples from peripheral blood of 35 healthy female individuals were positive for MGB1 transcript. In contrast MGB1 mRNA expression was detected in three of 36 (8%) peripheral blood of BC patients. CONCLUSIONS: Our preliminary results demonstrate that the detection of MGB1 transcript in peripheral blood of BC patients was specific but with low sensitivity. MGB1 overexpression by itself or in combination with Ki67 might be considered an index of BC progression

Processing of Self versus Non-Self in Alzheimer’s Disease

Despite considerable evidence for abnormalities of self-awareness in Alzheimer’s disease (AD), the cognitive mechanisms of altered self-processing in AD have not been fully defined. Here we addressed this issue in a detailed analysis of self/non-self-processing in three patients with AD. We designed a novel neuropsychological battery comprising tests of tactile body schema coding, attribution of tactile events to self versus external agents, and memory for self- versus non-self-generated vocal information, administered in conjunction with a daily life measure of self/non-self-processing (the Interpersonal Reactivity Index). Three male AD patients (aged 54–68 years; one with a pathogenic mutation in the Presenilin 1 gene, one with a pathogenic mutation in the Amyloid Precursor Protein gene, and one with a CSF protein profile supporting underlying AD pathology) were studied in relation to a group of eight healthy older male individuals (aged 58–74 years). Compared to healthy controls, all patients had relatively intact tactile body schema processing. In contrast, all patients showed impaired memory for words previously presented using the patient’s own voice whereas memory for words presented in other voices was less consistently affected. Two patients showed increased levels of emotional contagion and reduced perspective taking on the Interpersonal Reactivity Index. Our findings suggest that AD may be associated with deficient self/non-self differentiation over time despite a relatively intact body image: this profile of altered self-processing contrasts with the deficit of tactile body schema previously described in frontotemporal dementia associated with C9orf72 mutations. We present these findings as a preliminary rationale to direct future systematic study in larger patient cohorts

The X-ray emission of local luminous infrared galaxies

We study the X-ray emission of a representative sample of 27 local luminous infrared galaxies (LIRGs). The median IR luminosity of our sample is log L_IR/L_sun = 11.2, thus the low-luminosity end of the LIRG class is well represented. We used new XMM-Newton data as well as Chandra and XMM-Newton archive data. The soft X-ray (0.5-2 keV) emission of most of the galaxies (>80%), including LIRGs hosting a Seyfert 2 nucleus, is dominated by star-formation related processes. These LIRGs follow the star-formation rate (SFR) versus soft X-ray luminosity correlation observed in local starbursts. We find that ~15% of the non-Seyfert LIRGs (3 out of 20) have an excess hard X-ray emission relative to that expected from star-formation that might indicate the presence of an obscured AGN. The rest of the non-Seyfert LIRGs follow the SFR versus hard X-ray (2-10 keV) luminosity correlation of local starbursts. The non-detection of the 6.4 keV Fe K alpha emission line in the non-Seyfert LIRGs allows us to put an upper limit to the bolometric luminosity of an obscured AGN, L_bol <1043 erg s-1 . That is, in these galaxies, if they hosted a low luminosity AGN, its contribution to total luminosity would be less than 10%. Finally we estimate that the AGN contribution to the total luminosity for our sample of local LIRGs is between 7% and 10%.Comment: Accepted for Publication in A&A, 22 pages, 9 figure

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 &lt; .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