Explore the vast range of titles available.

During disease progression the cells that comprise solid malignancies undergo significant changes in gene copy number and chromosome structure. Colorectal cancer provides an excellent model to study this process. To indentify and characterize chromosomal abnormalities in colorectal cancer, we performed a statistical analysis of 299 expression and 130 SNP arrays profiled at different stages of the disease, including normal tissue, adenoma, stages 1-4 adenocarcinoma, and metastasis. We identified broad (> 1/2 chromosomal arm) and focal (< 1/2 chromosomal arm) events. Broad amplifications were noted on chromosomes 7, 8q, 13q, 20, and X and broad deletions on chromosomes 4, 8p, 14q, 15q, 17p, 18, 20p, and 22q. Focal events (gains or losses) were identified in regions containing known cancer pathway genes, such as VEGFA, MYC, MET, FGF6, FGF23, LYN, MMP9, MYBL2, AURKA, UBE2C, and PTEN. Other focal events encompassed potential new candidate tumor suppressors (losses) and oncogenes (gains), including CCDC68, CSMD1, POLR1D, and PMEPA1. From the expression data, we identified genes whose expression levels reflected their copy number changes and used this relationship to impute copy number changes to samples without accompanying SNP data. This analysis provided the statistical power to show that deletions of 8p, 4p, and 15q are associated with survival and disease progression, and that samples with simultaneous deletions in 18q, 8p, 4p, and 15q have a particularly poor prognosis. Annotation analysis reveals that the oxidative phosphorylation pathway shows a strong tendency for decreased expression in the samples characterized by poor prognosis.

BackgroundFibromyalgia (FM) is a common chronic widespread pain condition, also characterized by fatigue, sleep and mood disorders, with higher prevalence in women. Sexual function is an important feature in people’s well-being; its alterations include decreased sex drive, sexual satisfaction, orgasm, and arousal, as well as increased genital pain. Emerging but still too few studies observed a higher prevalence of sexual dysfunction in FM, especially related to depression.ObjectivesThe aim of this study was to evaluate sexual dysfunctions in a large cohort of FM women through Qualisex questionnaire, used in other rheumatic diseases but not yet validated for FM.MethodsWe consecutively enrolled women affected by FM (ACR 2016) referring to our out-patient clinic. Demographic and clinical examination as well as evaluation of severity of FM symptoms (R-FIQ, SSS and WPI) were assessed for each patient. Moreover, Hospital Anxiety and Depression Scale (HADS) and questionnaire for sexual dysfunction-Qualisex were anonymously administered. Qualisex questionnaire is composed by 10 questions on different items of sexual life with higher scores suggestive of greater negative impact of FM on sexual life.ResultsThe cohort was composed by 373 FM female patients, median age 49,1. Qualisex questionnaire was validated with Cronbach’s alpha test (0,878), median value 5,3. Women with lower grade of education (p=0,002), married (p<0,001) and with lower sexual feeling with partner (p<0,001) showed higher values of Qualisex. Menopause status, drug assumption and comorbidity did not influence patients’ sexual quality. High values of HADS-A and HADS-D showed a positive correlation with Qualisex Total (p<0,001 r=0,312; p<0,001 r=0,542 respectively) as well as high values of VAS pain, VAS fatigue and VAS dryness (p<0,001 r=0,438; p<0,001 r=0,375; p<0,001 r=0,70 respectively). Relationship duration also presented a positive correlation (p<0,001 r=0,202). Multivariate analysis observed a significantly influence of relationship duration, VAS pain, fatigue and dryness, HADS-A/D, R-FIQ and all specific items of Qualisex, on Qualisex Total correcting for patients’ age (p<0,001).ConclusionQualisex questionnaire represents a good test to evaluate sexual disorders in FM women. Different aspects contribute to sexual dysfunction both from a psychological (anxiety, depression, loss of self-esteem, decreased sexually attraction) and a physical (pain, fatigue etc..) point of view with an important impact of FM on sexual life and consequently a worsening of FM symptoms. Over a demotivation feeling, inability to live a “normal everyday life”, the reduced sexual function contributes to a bad quality of life. Other studies are needed to analyze which interventions, pharmacological and non (physical activity, psychotherapy), could improve the sexual aspect in the global contest of FM and to investigate this important aspect in FM male patients.References[1]Bazzichi L, Giacomelli C, Rossi A, Sernissi F, Scarpellini P, Consensi A, Bombardieri S. Fibromyalgia and sexual problems. Reumatismo. 2012 Sep 28;64(4):261-7.[2]Matarín Jiménez TM, Fernández-Sola C, Hernández-Padilla JM, Correa Casado M, Antequera Raynal LH, Granero-Molina J. Perceptions about the sexuality of women with fibromyalgia syndrome: a phenomenological study. J Adv Nurs. 2017 Jul;73(7):1646-1656.[3]Priori R, Giardina F, Gioia C, Iannuccelli C, Villa M, Gattamelata A, Conti F, Di Franco M, Curcio G. Cultural adaptation and preliminary validation of the Qualisex questionnaire for its use in patients with Sjögren’s syndrome and fibromyalgia in Italy. Clin Exp Rheumatol. 2022 Dec;40(12):2470-2471Table 1FM (n=373)Age (yrs), media ± SD49,1 ± 10,4Menopause, n (%)185 (49.6)Age menopause (yrs), media ± SD48,7 ± 7,3Replacement therapy, n (%)69 (18.3)Sexual relationship duration (yrs), media ± SD18,2 ± 11,7Qualisex TOTAL5,3 ± 2,7HADS A, media ± SD11,9 ± 4,3HADS D, media ± SD9,5 ± 4,1VAS dryness (0-10), media ± SD5,6 ± 3,4VAS pain (0-10), media ± SD6,8 ± 2,7VAS fatigue (0-10), media ± SD7,9 ± 1,9Figure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Background Interrogation of site-specific CpG methylation in circulating tumor DNAs (ctDNAs) has been employed in a number of studies for early detection of breast cancer (BrCa). In many of these studies, the markers were identified based on known biology of BrCa progression, and interrogated using methyl-specific PCR (MSP), a technique involving bisulfite conversion, PCR, and qPCR. Methods In this report, we are demonstrating the development of a novel assay (Multiplex Bisulfite PCR-LDR-qPCR) which can potentially offer improvements to MSP, by integrating additional steps such as ligase detection reaction (LDR), methylated CpG target enrichment, carryover protection (use of uracil DNA glycosylase), and minimization of primer-dimer formation (use of ribose primers and RNAseH2). The assay is designed to for breast cancer-specific CpG markers identified through integrated analyses of publicly available genome-wide methylation datasets for 31 types of primary tumors (including BrCa), as well as matching normal tissues, and peripheral blood. Results Our results indicate that the PCR-LDR-qPCR assay is capable of detecting ~ 30 methylated copies of each of 3 BrCa-specific CpG markers, when mixed with excess amount unmethylated CpG markers (~ 3000 copies each), which is a reasonable approximation of BrCa ctDNA overwhelmed with peripheral blood cell-free DNA (cfDNA) when isolated from patient plasma. The bioinformatically-identified CpG markers are located in promoter regions of NR5A2 and PRKCB , and a non-coding region of chromosome 1 (upstream of EFNA3 ). Additional bioinformatic analyses would reveal that these methylation markers are independent of patient race and age, and positively associated with signaling pathways associated with BrCa progression (such as those related to retinoid nuclear receptor, PTEN, p53, pRB, and p27). Conclusion This report demonstrates the potential utilization of bisulfite PCR-LDR-qPCR assay, along with bioinformatically-driven biomarker discovery, in blood-based BrCa detection.

Coral reefs are threatened by climate change, overfishing, and pollution. Artificial reefs may provide havens for corals, both to escape warming surface waters and to assist in the geographic migration of corals to more habitable natural reef conditions of the future. The largest artificial reefs have been generated by nearly 2000 shipwrecks around the world, but the coral diversity on these wrecks is virtually unknown. Ship size and hull material, location relative to natural reef, time since sinking, ocean currents, and water depth may affect coral diversity. As a test of the biodiversity capacity of very large sunken structures relative to surrounding natural reef, we carried out technical diver-based surveys to quantify genus-level coral diversity on 29 warships sunk in Bikini Atoll and Chuuk Lagoon. We also assessed whether ship length, as an index of substrate availability, and water depth, as an indicator of light and temperature, can serve as predictors of coral diversity. We surveyed a total of 9105 scleractinian corals. The total number of genera identified at Bikini was 34, and at Chuuk it was 51, representing 67% and 72% of genera found on natural reefs at Bikini and Chuuk, respectively. Ship length, but not water depth, was positively correlated with relative abundance and richness at the genus level. Our results suggest that very large wrecks can serve as havens for reef-building corals with a broad genetic diversity, expressed at the genus level, commensurate with corals found on neighboring natural reefs. The role of large artificial reefs could include protecting coral biodiversity from warming surface waters.

Global climate models provide useful tools to forecast large‐scale anthropogenic trends and the impacts on ocean physics and marine biology and chemistry. Due to coarse spatial resolution, they typically lack the ability to represent important regional processes while underestimating mesoscale variability and vertical mixing. This means they provide limited value when it comes to regional climate projections. We developed a regional submesoscale‐permitting physical/biogeochemical model to dynamically downscale the output of a CMIP6 Earth System Model for three different Socioeconomic Pathways for the main Hawaiian Islands. We describe the methodology for downscaling the CMIP6 ocean physics and biogeochemistry along with atmospheric conditions in order to offline nest a regional model. We expect the large‐scale spatial and temporal features of the global model to be retained by the regional model, while adding representation of the regional processes that are crucial to understanding climate change on a local scale. We compare the regional model representation against both observed data and a regional reanalysis over the first two decades of the century. We show that the regional model maintains the large‐scale trends and interannual variability provided by the CMIP6 model while well‐representing the regional dynamics that drive the short‐term variability. To better illustrate the benefit of the downscaling, we present preliminary analysis of the downscaled results to examine climate impacts on the island corals that are not resolved by the global models. This analysis reveals that coastal corals are likely to experience unprecedented ocean acidification and substantial warming over the course of the century. Plain Language Summary Climate models play an important role in projecting the changes in the ocean that may result from human‐induced climate change; however, these models lack the ability to represent critical features important to regional localities. This means that high‐resolution regional models are required to understand the impacts of climate change important to local communities. We describe how to downscale climate model solutions such that they can be used by high‐resolution regional models to project local impacts of climate change. Our application is for the main Hawaiian Islands in the Pacific ocean that are highly dynamic but are missing from climate models. We also provide preliminary results of these projections that show regional impact on the island corals due to climate change. Key Points The first dynamically downscaled submesoscale permitting future climate projections for the main Hawaiian Islands are presented A careful treatment of global model output is critical to capture essential local oceanographic characteristics Hawai'i’s near‐surface ocean is likely to experience unprecedented acidification and substantial warming over the course of the century

Abatacept (ABA) is a biological drug approved for the treatment of rheumatoid arthritis (RA) patients that, by working on CTLA4, can inhibit T-cell activation. Randomized controlled trials have demonstrated both the efficacy and a good safety profile, characterized by a lower infectious risk in comparison with other biological DMARDs, in RA patients. In a real-life setting, the drug retention rate could be considered as a surrogate of drug effectiveness. Data from the literature reported a retention rate of ABA ranging from 55 to 76% at 12 months and from 54 to 64% at 24 months (1-3). In the present longitudinal analysis, we evaluated the retention rate of ABA in a large monocentric RA cohort. We enrolled consecutive RA patients starting treatment with intravenous (IV) or subcutaneous (SC) ABA according to the standard of care. All the patients fulfilled the 2010 ACR/EULAR classification criteria for RA. For each patient, we collected demographic parameters, serological status, previous and concomitant treatments, and disease activity by DAS28 with C reactive protein (DAS28-CRP). All the patients were assessed at baseline, and after 4 and 12 months (T4 and T12, respectively). The reasons for withdrawal of treatment were registered and classified as primary or secondary inefficacy or adverse events (AEs). Kaplan-Meier statistical analysis has been done to evaluate the survival of the treatment in patients with at least 12 months follow-up. We evaluated 161 patients [M/F 21/140; median age 67 years (IQR 21.7), median disease duration 180 months (IQR 161)]. RF was positive in 70.3% of patients, ACPA in 66.4%. ABA was the first biological DMARD in 66 patients (41%). At baseline, the median DAS28-CRP was 4.3 (IQR 1.6) and ABA was administered in association with MTX in 96 patients (59.6%). One hundred-eleven patients (68.9%) started SC ABA [M/F 16/95; median age 64.5 years (IQR 21.5), median disease duration 156 months (IQR 132)], the remaining 50 IV ABA [M/F 5/45, median age 71 years (IQR 60.2), median disease duration 187 months (IQR 157)]. Median age and disease duration were significantly higher in patients receiving IV in comparison with SC ABA (p=0.008 and p=0.03, respectively). We found a significant reduction of DAS28-CRP values during the follow-up in comparison with baseline [4 months: median 3.5 (IQR 1.9), p<0.0001; 12 months: median 3.2 (IQR 1.4), p<0.0001]. Seven patients were lost to follow-up, in the remaining 154 patients a median treatment duration of 33 months (IQR 49) was registered. Data on drug survival are reported in Figure 1A: at 12 months, 92% of patients persisted on treatment; this percentage decreased to 78.2% at 24 months and to 67.9% at 36 months. Furthermore, we did not find any differences in drug survival either with respect to SC vs IV administration (12 months: 93.7% versus 88.6%; 24 months 78.9% versus 72.6%; 36 months 63.7% versus 72.6%; Figure 1B) or according to the association with MTX. Concerning the withdrawal reasons, 46 patients (29.9%) stopped ABA due to inefficacy (primary in 28, secondary in 18), 11 patients (7.1%) due to AEs, and 7 for inadequate adherence (4.5%). Finally, 10 patients switched from IV to SC administration, due to patient's preference. In our monocentric RA cohort, we have observed a high retention rate of ABA at both 12 and 24 months, confirming the good profile of this drug in terms of effectiveness and safety, irrespective of the route of administration and association with MTX. [1]Cagnotto, Arthritis Res Ther 2020; (2) Salmon, J Clin Med 2020; Westhovens, Rheumatol Int 2020. I would like to acknowledge Dr. F. Ceccarelli, for her patience. None declared

Objective: Highly porous titanium cups have been recently introduced, with contradictory outcomes. A retrospective consecutive case series involving bilateral metachronous total hip arthroplasties (THA) performed with 2 different cups, i.e., Fixa (F) and Fixa Ti-Por (T) (Adler Ortho, Milan, Italy), and the same stem, was evaluated. T sockets, manufactured using electron beam melting, were supposed to prove superior in terms of clinical results, survival rates, and radiographic parameters in comparison to hydroxyapatite-coated F cups with conventional porosity. Subjects and Methods: Twenty-four bilateral metachronous THAs with an F cup on one side and a T socket on the other side were evaluated. Preoperative and postoperative Harris hip scores (HHS) were collected for every patient. Radiographic signs of loosening were assessed. The radiographic signs of osseointegration (radiolucent lines, superolateral buttress, inferomedial buttress, radial trabeculae, and stress shielding) were evaluated. Results: No intraoperative complications occurred. The mean HHS score was excellent and comparable in both groups. At the mean follow-up of 134 months (F) and 79 months (T), no cup or liner revisions were performed. No radiographic signs of loosening were reported. All of the patients revealed 3 parameters of good bony ingrowth at least. Both groups showed similar radiographic parameters regarding osseointegration, which were stable over the time. Stress shielding was more evident in the T cohort (p =0.07). Conclusion: Highly porous titanium cups produced using an additive manufacturing and electron beam melting technology achieved reliable midterm clinical and radiographic results not inferior to those of second-generation cups.

According to the available literature, the current distribution limits of L. sceleratus correspond to the north Aegean Sea and Tunisia, whilst this species has not yet been reported from Italy

SG epithelial cells (SGEC) play a key role in sustaining inflammation in Sjӧgren Syndrome (SS), which is indeed termed an ‘autoimmune epithelitis’. However, the mechanisms responsible for the inflammatory activation of SGEC remain largely undetermined. Our line of research indicates that SGECs in SS exhibit profound changes in cell energy metabolism as indicated by aberrant expression of autophagy [1]. Inhibitions of autophagic process results in a down regulation of SGECs activation [1], thus indicating a crucial role of SGEC energy metabolism in the induction of autoimmune epithelitis. Aim of this study is to characterize metabolic changes occurring in SS SGECs and dissect the link between these changes and their acquired pro-inflammatory function. SGECs were isolated from minor SG biopsies deriving from patients with SS and sicca. Intracellular metabolomic analysis was performed on direct ex vivo isolated primary SGECs. As read out of functional activation of SS SGECs, supernatants from SGECs coltures were collected to perform ELISA test in order to evaluate the expression of the pro-inflammatory mediator IL-6. Principal component analysis (PCA) of high-throughput metabolomics analysis of sicca (n=7) and SS (n=7) SGECs revealed a separation along the component 1 axis (46.6% of variance) indicating profound differences in the intracellular metabolome (Figure 1a). Unsupervised clustering analysis of metabolites revealed profound metabolic differences between SS and (n=7) sicca (n=7) SGECs (Figure 1b). Analysis of selected metabolites confirmed a shift towards increased glycolysis and TCA cycle activation in SS SGECs (Figure 1c). Supernatant concentrations of IL-6 were higher in SS (n=21) compared to sicca (n=14) SGECs (Figure 1d). SGECs from SS patients display altered cell energy metabolism with evidence of increased glycolysis and activated TCA cycle. A metabolic driven pro-inflammatory status of SS SGECs seems confirmed by increased basal expression of IL-6. Validation of our metabolomic results, along with transcriptomic and epigenetic studies, is currently ongoing in SGECs from SS and sicca to dissect the link between changes in cell energy metabolism and their acquired pro-inflammatory phenotype. [1]Colafrancesco S, et al. Maladaptive Autophagy in the Pathogenesis of Autoimmune Epithelitis in Sjögren's Syndrome. Arthritis Rheumatol. 2022;74(4):654-664. NIL. None Declared. [Display omitted]