Outcome of Very Late Relapse in Patients with Hodgkin's Lymphomas

Recurrences of Hodgkin's Lymphoma (HL) 5 years after the initial therapy are rare. The aim of this study is to report a single centre experience of the clinical characteristics, outcome, and toxicity of pts who experienced very late relapses, defined as relapses that occurred 5 or more years after the achievement of first complete remission. Of 532 consecutive pts with classical HL treated at our Institute from 1985 to 1999, 452 pts (85%) achieved a complete remission. Relapse occurred in 151 pts: 135 (29.8%) within 5 years and 16 over 5 years (3.5%, very late relapses). Very late relapses occurred after a median disease-free interval of 7 years (range: 5–18). Salvage treatment induced complete remission in 14 pts (87.5%). At a median of 4 years after therapy for very late relapse, 10 pts (63%) are still alive and free of disease and 6 (37%) died (1 from progressive HL, 1 from cardiac disease, 1 from thromboembolic disease, 1 from HCV reactivation, and 2 from bacterial infection). The probability of failure-free survival at 5 years was 75%. The majority of deaths are due to treatment-related complications. Therapy regimens for very late relapse HL are warranted to minimize complications

Effect of Integration of Linseed and Vitamin E in Charolaise × Podolica Bulls’ Diet on Fatty Acids Profile, Beef Color and Lipid Stability

Dietary supplementation with oilseeds improves the fatty acid profiles of meat, but results are often inconsistent. This study aimed to assess the effects of dietary linseed and vitamin E supplementation on fatty acid profile, cholesterol content and color stability of beef samples. Dorsal subcutaneous fat samples were subjected to lipid stability assessment. Eighteen young bulls (385 ± 15 kg BW, age 8–9 months) were allocated into three homogeneous groups, each receiving ad libitum wheat straw and concentrate only (CON = 5.5 kg/day), concentrate with linseed (LIN = 80 g/kg, i.e., 440 g/head/day), and concentrate with linseed plus vitamin E (L + E = 80 g/kg, i.e., 440 g/head/day + 2500 IU/head/day of Vitamin E). Group L+E showed significantly lower cholesterol content, lower n-6/n-3 ratio and a higher PUFA percentage compared to the CON group. Meat color was affected by feeding LIN with a decrease in a*, b*, and C* compared to the CON group. The experimental diets increased H◦ values compared to the CON group. A positive effect of vitamin E in protecting lipids of dorsal subcutaneous depots from oxidation was detected in group L+E compared to group LIN. The supplementation with extruded linseeds in the diet had positive effects on the nutritional profile of the meat. When vitamin E was included, linseed did not alter the color of meat, and the lipid stability of the subcutaneous fat improved

Effect of Pegbovigrastim on Hematological Profile of Simmental Dairy Cows during the Transition Period

Pegbovigrastim is a long-acting analog of recombinant bovine granulocyte colony-stimulating factor, that promotes and increases the count and functionality of polymorphonuclear cells in dairy cows. The present study aimed to explore, for the first time in Simmental cows, the clinical and hematological effect of pegbovigrastim during the transition period (TP). Cows were randomly assigned into two groups: treated group (PEG; n = 16) received pegbovigrastim at approximately 7 days before expected parturition and within 6 h after calving, and control group (CTR; n = 16) received saline solution. Blood samples were obtained at −7, 0, 1, 3, 7, 14, 21, and 30 days relative to calving. PEG group showed white blood cells (WBC) count consistently higher compared with CTR group (p < 0.001) until to 3 weeks after calving. Neutrophils remained higher in PEG group (p < 0.001) up to three weeks after calving, compared with CTR group, with slight increment of band cells. Moreover, PEG group displayed a lower index of myeloperoxidase at 1, 3, and 7 days after calving (p < 0.01) compared with CTR. Basophils and lymphocytes showed a similar trend to those observed for neutrophils at 1 day after calving in PEG group. Finally, monocytes remained markedly elevated until 3 days after calving in PEG compared to CTR group (p < 0.001), whereas in PEG group, eosinophils population showed lower percentage values at 1 and 3 days after calving but higher values at 30 days compared with CTR group. PEG group was characterized by lower red blood cells (RBCs) count compared with CTR group (p < 0.05) and higher % of red cell volume distribution width (RDW) from week 2 and mean corpuscular volume (MCV) at 30 days after calving. In addition, the mean platelet volume (MPV) was significantly higher in PEG group at calving, 1, 3, and 7 days after calving compared with CTR group (p < 0.05). For the first time, we described the effect of pegbovigrastim in a breed not specialized exclusively in milk production as Holstein, but with dual purpose (meat and milk), evaluating the complete hematological profile in cows during the transition period. These results provide evidence on the proliferative effect of pegbovigrastim on WBC in Simmental breed highlighting its possible side effect on RBCs

Pair distribution function analysis and Mössbauer study of defects in microwave-hydrothermal LiFePO 4

Olivine-type LiFePO 4 is nowadays one of the most important cathode materials of choice for high-energy lithium ion batteries. Its intrinsic defectivity, and chiefly the so-called lithium iron anti-site, is one of the most critical issues when envisaging electrochemical applications. This paper reports a combined diffractometric (Synchrotron Radiation XRD with Rietveld and PDF analyses) and spectroscopic (Mössbauer) approach able to give a thorough characterization of the material defectivity. Such analytical procedure has been applied to a sample prepared following an innovative microwave-assisted hydrothermal synthesis route that, in a few minutes, allowed us to obtain a well crystallized material. PDF analysis, which is applied for the first time to this type of battery material, reveals the presence of disorder possibly due to Li/Fe exchange or to a local symmetry lowering. A 5% amount of iron on the lithium site has been detected both by PDF as well as by Mössbauer spectroscopy, which revealed a small percentage of Fe 3+ on the regular sites. © 2012 The Royal Society of Chemistry

The Quality of Five Natural, Historical Italian Cheeses Produced in Different Months: Gross Composition, Fat-Soluble Vitamins, Fatty Acids, Total Phenols, Antioxidant Capacity, and Health Index

Five natural historic cheeses of Southern Italy were investigated-Caciocavallo Palermitano (CP), Casizolu del Montiferru (CdM), Vastedda della Valle del Belìce (VVB), Pecorino Siciliano (PS), and Caprino Nicastrese (CN)-which are produced with raw milk and with traditional techniques and tools, from autochthonous breeds reared under an extensive system. The effects of the month of production on gross composition, MUFA, PUFA, PUFA-ω6, PUFA-ω3, α-tocopherol, retinol, cholesterol, TPC, TEAC, and GHIC were evaluated. In CP, CLA, TPC, and GHIC were higher in April than in February. CdM showed higher values in terms of fat, saturated fatty acids, PUFA-ω3, α-tocopherol, TEAC, and GHIC in May than in February and September, while low values in terms of protein, moisture, and CLA were found. In VVB, MUFA, PUFA-ω6, and α-tocopherol increased in June compared with April; conversely, protein, FRAP, and TEAC were higher in April. In PS, protein, CLA, PUFA, PUFA-ω3, α-tocopherol, and GHIC increased in May compared with January; on the contrary, moisture, NaCl, and TEAC showed high values in January. CN showed higher values in terms of PUFA, PUFA-ω6, PUFA-ω3, TPC, TEAC, and GHIC in April and June compared with January. It is shown that each cheese is unique and closely linked to the production area. Cheeses produced in the spring months showed a high nutritional quality due to the greatest presence of healthy compounds originating from an extensive feeding system

Low-dose radiotherapy in diffuse large B-cell lymphoma

Low-dose radiotherapy (LDRT) given in 2 x 2 Gy is a highly effective and safe treatment for palliation of indolent lymphomas. Otherwise, very little regarding the use of LDRT for diffuse large B-cell lymphoma (DLBCL) has been investigated. We designed a phase 2 trial of LDRT in patients with DLBCL with indication for palliative radiation. Low-dose radiotherapy was administered on symptomatic areas only. Clinical response was assessed 21 days after LDRT and defined as reduction >50% of maximum diameter of the radiated lesions. Quality of life was scored by the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Tumor subtype (germinal center B-cell type versus activated B-cell type) and the presence of TP53 mutations in pathologic specimens of the target lesion were also evaluated. Twenty-three of twentyfive radiated patients were evaluable for response. and 2 died of disease before the visit at 21 days. The overall response rate was 70% (16 of 23 patients), with 7 complete responses and 9 partial responses (mean duration of response. 6 months; range, 1-39 months). Fifteen patients answered to the QLQ-C30 questionnaires, and an improved quality of life was documented in 9 cases. TP53 mutations were detected in 2 of 6 (33%) nonresponders and in none of the responders (P = .12). Germinal center B-cell type responded better than activated B-cell type (response rate was 83% and 29%, respectively, P = .01). These findings indicate that LDRT is effective for palliation in patients with DLBC

The Sea Urchin sns5 Chromatin Insulator Improves the Likelihood of Lentiviral Vectors in Erythroid Milieu By Organizing an Independent Chromatin Domain at the Integration Site

Retroviral vectors are currently the most suitable vehicles for therapeutic gene transfer in hematopoietic stem cells. However, these vectors are known to integrate rather randomly throughout the genome, suffering the so called chromosomal position effects (PE). Such a critical occurrence most probably depends upon the ability of heterochromatin to spread in the inserted vector sequences. Moreover, the use of transgenes imply genotoxicity effects, since the cis-regulatory sequences harbored by the vector can disturb the proper transcription of the resident genes neighboring the integration site, potentially leading to malignant transformation. Due to their enhancer blocker activity, the incorporation of chromatin insulators in flanking position to the transferred unit can reduce the mentioned dangerous effects. Moreover, by acting as barriers to the spread of heterochromatin, chromatin insulators can also mitigate vector silencing. We have previously shown that the sea urchin sns5 chromatin insulator activity is conserved in mouse and human erythroid milieu: it blocks the βglobin-LCR-HS2 enhancer/globin promoter interaction when placed between them. In addition, when placed in flanking location of a γ-retrovirus vector, sns5 impedes PE variegation and improves vector-specific expression following integration in the erythroid genome. Importantly, by binding both erythroid-specific and ubiquitous factors, sns5 favors the accumulation inside the provirus locus of epigenetic marks commonly associated to an euchromatic state (Acuto S. et al., BCMD 2005; D'Apolito D. et al., 2009; Di Caro D. et al., J Mol Biol 2004; Cavalieri V. et al., NAR 2009). In this study we extend these findings, demonstrating that sns5 works as chromatin insulator also when placed in flanking position of a GFP transgene contained in a lentivirus vector (LV-GFP). A large panel of mouse erythroleukemic clones (MELC) was generated after transduction with uninsulated and sns5 -insulated LV-GFP. Individual clones were screened for single vector integrants (by Q-PCR), and for GFP-expression (by cytofluorimetry). Our results shown that the inclusion of the sns5 element in a forward orientation increased the fraction of vector expressing cells (89% for the insulated vector vs 42% for the uninsulated ones). The clonal variegation of expression, assessed as frequency of clones that showed a percentage of GFP-negative cells in the progeny, decreased in clones transduced with the insulated vectors (7.4% vs 13,9%). It has been suggested that chromatin insulators could shape the architecture of topologically independent chromosome domains. High resolution mapping of chromosomal domains in drosophila and higher eukaryotes highlighted that chromatin insulators play a critical role in shaping the architectural genome organization both in a local chromosome environment and in long range chromosomal interaction. Intriguingly, by using the Chromosome Conformation Capture (3C) technology, we demonstrated that the sns5 -flanked LV-GFP integrated at a single copy in the erythroid cell genome is organized into an independent chromatin loop at the integration site. Worth to mention, no looping was detected in the absence of sns5, indicating that the two flanking copies of sns5 are specifically involved in the reorganization of the chromatin structure at the provirus locus. In conclusion our results not only confirm the conserved and striking boundary function of sns5, but also provide a new clue concerning the molecular mechanism that allows this function to occur. On these basis, our findings reassure the use of sns5 to improve both efficacy and safety of lentiviral vectors for gene therapy

Il mese di produzione influenza la qualit\ue0 di formaggi tipici?

Il settore lattiero-caseario mediterraneo rappresenta una delle pi\uf9 importanti attivit\ue0 legate al lavoro delle terre montane e marginali e alla produzione di prodotti tipici e di qualit\ue0. Un prodotto \u201ctipico\u201d \ue8 il risultato di diversi fattori strettamente legati all\u2019origine geografica e alle tradizioni sociali e culturali dell\u2019area di produzione. Tali prodotti sono da sempre uno strumento per valorizzare la biodiversit\ue0, la cultura e l\u2019economia di definite aree mediterranee. L\u2019Unione Europea riconosce ufficialmente questa diversificazione di prodotto attraverso l\u2019attribuzione di marchi di qualit\ue0 a denominazione di origine protetta (DOP) e a indicazione geografica protetta (IGP). Nella politica agroalimentare italiana \ue8 presente anche il marchio di prodotto agroalimentare tradizionale (TAP). Recentemente, 15 formaggi storici naturali del Sud Italia, identificati come la \u201cselezione AGER (Agroalimentare e ricerca)\u201d, hanno ricevuto attenzione nel progetto dal titolo \u201cCanestrum casei- Sviluppo di un modello sinergico finalizzato alla qualificazione e valorizzazione dei formaggi storici naturali del Sud Italia nelle regioni Sicilia, Sardegna, Calabria, Basilicata e Campania\u201c. Il progetto mira a qualificare e valorizzare questi formaggi storici e a ridare dignit\ue0 agli allevatori e ai produttori di questi formaggi, meno conosciuti dai consumatori e spesso a rischio di estinzione per oggettive difficolt\ue0 di qualificazione e valorizzazione sul mercato. In questo lavoro vengono studiati 5 dei 15 formaggi della selezione AGER. Il Caciocavallo Palermitano TAP (CP) \ue8 un formaggio a pasta dura, prodotto nella regione Sicilia in provincia di Palermo a 700-1000 m s.l.m. \ue8 un formaggio a pasta filata ottenuto dal latte bovino crudo delle razze Cinisara, Pezzata Rossa, Bruna e meticci, ed \ue8 ancora prodotto con tecniche tradizionali utilizzando tipici strumenti in legno. La Vastedda della Valle del Bel\uecce DOP (VVB), un formaggio a pasta molle e filata, prodotto nella zona collinare (300 m s.l.m.) della Sicilia occidentale. \uc8 prodotto con latte ovino crudo della razza ovina autoctona Valle del Bel\uecce. Questo formaggio viene prodotto utilizzando attrezzature tradizionali in legno e applicando la tecnologia della filatura, che gli conferisce unicit\ue0. Il Pecorino Siciliano DOP (PS) \ue8 un prodotto caseario a pasta dura proveniente dalla zona montana (700 m s.l.m.) della Sicilia centrale e dalla zona collinare (400 m s.l.m.) della Sicilia occidentale. Il Casizolu del Montiferru TAP(CdM) \ue8 un formaggio a pasta dura prodotto nella regione Sardegna nella zona montana (1050 m s.l.m.) del Montiferru e nella zona collinare (500 m s.l.m.) del Montiferru/Guilcer. Si tratta di un formaggio a pasta filata ottenuto da latte bovino crudo delle razze Sardo-Modicana e Bruno-Sarda, allevate in regime estensivo durante l\u2019anno, utilizzando tecniche tradizionali con attrezzature in rame e legno. Il Caprino Nicastrese (CN) \ue8 un formaggio a pasta semidura prodotto nella regione Calabria nelle zone collinari (300-600 m s.l.m.) e montane (601-1200 m s.l.m.) circostanti Nicastro-Lamezia Terme, in provincia di Catanzaro. Si ottiene dal latte crudo della razza caprina autoctona Nicastrese, utilizzando una tecnica tradizionale con attrezzature in legno e acciaio. Questi cinque formaggi sono prodotti in aree ristrette, condizioni pedoclimatiche e attivit\ue0 antropiche (definite come uniche e non riproducibili altrove) che, cos\uec come il territorio e le abitudini, sono conformi alla storia e alla tradizione. Uno degli obiettivi specifici del progetto \u201cCanestrum Casei\u201d \ue8 stato quello di realizzare un\u2019indagine conoscitiva sulla qualit\ue0 di questi formaggi per adempiere alla caratterizzazione della selezione dei formaggi AGER uniformando le informazioni di maggior interesse per i consumatori rispetto alle specificit\ue0 produttive regionali. In particolare, nel presente lavoro, \ue8 stata valutata l\u2019influenza del periodo di produzione sulla composizione chimica, le caratteristiche nutrizionali, il contenuto di polifenoli, la capacit\ue0 antiossidante totale e l\u2019indice di salute dei cinque formaggi tradizionali citati. Pertanto i cinque foraggi tipici del meridione italiano, sopra descritti, sono stati studiati per valutare gli effetti del mese di produzione sulla composizione lorda, MUFA, PUFA, PUFA-\u3c96, PUFA-\u3c93, \u3b1-tocoferolo, retinolo, colesterolo, TPC, TEAC e GHIC. In CP, CLA, TPC e GHIC erano pi\uf9 alti in aprile che in febbraio. Il CdM ha mostrato valori pi\uf9 alti in termini di grassi, acidi grassi saturi, PUFA-\u3c93, \u3b1-tocoferolo, TEAC e GHIC in maggio rispetto a febbraio e settembre, mentre sono stati trovati valori bassi in termini di proteine, umidit\ue0 e CLA. In VVB, MUFA, PUFA-\u3c96, e \u3b1-tocoferolo sono aumentati in giugno rispetto ad aprile; al contrario, proteine, FRAP, e TEAC erano pi\uf9 alti in aprile. In PS, proteine, CLA, PUFA, PUFA-\u3c93, \u3b1-tocoferolo e GHIC sono aumentati in maggio rispetto a gennaio; al contrario, umidit\ue0, NaCl e TEAC hanno mostrato valori elevati in gennaio. CN ha mostrato valori pi\uf9 alti in termini di PUFA, PUFA-\u3c96, PUFA-\u3c93, TPC, TEAC e GHIC in aprile e giugno rispetto a gennaio. \uc8 dimostrato che ogni formaggio \ue8 unico e strettamente legato alla zona di produzione. I formaggi prodotti nei mesi primaverili hanno mostrato un\u2019alta qualit\ue0 nutrizionale dovuta alla maggiore presenza di composti salutari provenienti da un sistema di alimentazione estensiva. I risultati ottenuti da questo studio hanno mostrato che le caratteristiche nutrizionali dei formaggi tradizionali valutati, cio\ue8 il contenuto di acidi grassi, il contenuto di vitamine liposolubili e polifenoli, la capacit\ue0 antiossidante totale e l\u2019indice di salute, erano influenzati dal mese di produzione. In generale, la pi\uf9 alta qualit\ue0 nutrizionale era legata alla maggiore presenza di composti salutari, che provenivano dal pascolo nei mesi primaverili di produzione del formaggio. Ogni formaggio \ue8 unico e strettamente legato alla zona di produzione, anche se un\u2019alta variabilit\ue0, dovuta a numerosi fattori \u2013 tra cui specie, razza, alimentazione, tipo di suolo, posizione geografica, clima e tecnologia di produzione \u2013 caratterizza i parametri analizzati in ogni formaggio

The surgical treatment of non-metastatic melanoma in a Clinical National Melanoma Registry Study Group (CNMR): a retrospective cohort quality improvement study to reduce the morbidity rates

Background: Reproducible, high-quality surgery is a key point in the management of cancer patients. Quality indicators for surgical treatment of melanoma has been presented with benchmarks but data on morbidity are still limited. This study presents the quality indicators on morbidity after surgical treatment for non-metastatic skin melanoma in an Italian registry. Methods: Data were extracted from the Central National Melanoma Registry (CNMR) promoted by the Italian Melanoma Intergroup (IMI). All surgical procedures (WE, SNLB or LFND) for non-metastatic skin melanoma between January 2011 and February 2017 were evaluated for inclusion in the study. Only centers with adequate completeness of information (&gt; 80%) were included in the study. Short-term complications (wound infection, dehiscence, skin graft failure and seroma) were investigated. Results: Wound infection rate was 1.1% (0.4 to 2.7%) in WE, 1.3% (0.7 to 2.5%) in SLNB and 4.1% (2.1 to 8.0%) in LFND. Wound dehiscence rate was 2.0% (0.8 to 5.1%) in WE, 0.9% (0.2 to 3.0%) in SLNB and 2.8% (0.9 to 8.6%) in LFND. Seroma rate was 4.2% (1.5 to 11.1%) in SLNB and 15.1% (4.6 to 39.9%) in LFND. Unreliable information was found on skin graft failure. Conclusions: Our findings contribute to available literature in setting up the recommended standards for melanoma centers, thus improving the quality of surgery offered to patients. A consensus on the core issues around surgical morbidity is needed to provide practical guidance on morbidity prevention and management