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Galileo High Accuracy Service (HAS) corrections are broadcast through the E6B signal using a high-parity vertical Reed-Solomon encoding scheme, which reduces message recovery time and improves transmission reliability. To recover HAS corrections, it is thus necessary to invert the encoding process and interpret the decoded bits. In order to foster HAS adoption and facilitate experimentation with HAS corrections, a Galileo HAS Parser (GHASP) has been developed. GHASP is available open-source and supports different input data types from different receiver manufacturers. Decoded corrections are provided in Comma-Separated Values files, which can be directly loaded using common data-science languages. In this way, corrections are readily available and can be used not only for Precise Point Positioning (PPP) applications but also for scientific analysis such as clock characterization using the Allan Deviation.

Representative models are needed to screen new therapies for patients with cancer. Cancer organoids are a leap forward as a culture model that faithfully represents the disease. Mouse-derived cancer organoids (MDCOs) are becoming increasingly popular, however there has yet to be a standardized method to assess therapeutic response and identify subpopulation heterogeneity. There are multiple factors unique to organoid culture that could affect how therapeutic response and MDCO heterogeneity are assessed. Here we describe an analysis of nearly 3500 individual MDCOs where individual organoid morphologic tracking was performed. Change in MDCO diameter was assessed in the presence of control media or targeted therapies. Individual organoid tracking was identified to be more sensitive to treatment response than well-level assessment. The impact of different generations of mice of the same genotype, different regions of the colon, and organoid specific characteristics including baseline size, passage number, plating density, and location within the matrix were examined. Only the starting size of the MDCO altered the subsequent growth. These results were corroborated using ~ 1700 patient-derived cancer organoids (PDCOs) isolated from 19 patients. Here we establish organoid culture parameters for individual organoid morphologic tracking to determine therapeutic response and growth/response heterogeneity for translational studies.

ObjectiveTo evaluate the relationship between infarct pattern, inferred stroke mechanism and risk of recurrence in patients with ischaemic stroke. The question is clinically relevant to optimise secondary stroke prevention investigations and treatment.DesignWe conducted a retrospective analysis of the dabigatran treatment of acute stroke II (DATAS II) trial (ClinicalTrials.gove NCT NCT02295826), in which patients underwent diffusion-weighted imaging (DWI) at baseline and 30 days after randomisation to one of two antithrombotic therapies. Patients were classified as embolic, isolated small subcortical infarcts or transient ischaemic attack TIA (no infarct) at baseline and day 30. Stroke mechanism was determined by traditional and modified (based on DWI lesion findings) Trial of Org 10 172 in Acute Stroke Treatment (TOAST) criteria (DWI-TOAST).SettingMulticentre (6) tertiary acute stroke treatment hospitals.Participants305 adults with minor ischaemic stroke (National Institutes of Health Stroke Scale (NIHSS) score≤9).ResultsOf 305 patients, 148 had embolic pattern infarcts, 93 were isolated small subcortical infarcts and 64 had no infarct on baseline MRI (TIA). In the absence of DWI, TOAST classification indicated the mechanism was cryptogenic in 147 patients (48.2%), and small-vessel occlusion in 127 (41.6%). Using, DWI-TOAST, the number of cryptogenic strokes decreased to 123 (40.3%), and the number of small-vessel occlusion strokes increased to 151 (49.5%). Recurrent infarcts were seen in 13% of patients with an MRI-defined embolic infarct pattern and cryptogenic mechanism on DWI-TOAST. The relative risk of recurrent infarction in patients with undetermined aetiology was increased compared with other categories (standardised coefficient=1.0 (0.1, 1.9), p=0.029). The topography of recurrent infarcts was most often embolic (60.9%), but in 39.1% an isolated small subcortical infarct was seen.ConclusionsDefinitive identification of infarct topography with DWI has a significant impact on infarct mechanism classification. The variable relationship between baseline infarct patterns, clinical presentation and recurrent infarct distribution is a challenge to both the lacunar and embolic stroke of uncertain source (ESUS) concepts. Irrespective of aetiological classification, patients with MRI-defined cryptogenic embolic pattern infarcts are at high risk for recurrent events.Trial registration numberLinked to the DATAS II trial. ClinicalTrials.gov ID NCT02295826.

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.

Fibromyalgia (FM) is a chronic syndrome clinically characterized by widespread musculoskeletal pain associated with symptoms like fatigue, sleep disturbances and cognitive impairment. Prevalence is higher in females but the 2010/2011 and 2016 revisions of the American College of Rheumatologist (ACR) criteria reduced prevalence differences and the actual female:male ratio is approximately 3:1. Even if in the last years some studies have been conducted regarding gender differences in FM, disease severity is still assessed using questionnaires, such as the Revised Fibromyalgia Impact Questionnaire (FIQR), designed for female patients and validated through a predominantly female sample. Aim of this pilot study was to compare the 21 items of the FIQ-R among male and female patients in order to evaluate the possible existence of a gender bias. In this case control study, all the consecutive patients with a diagnosis of FM (2016 ACR criteria) referring to our out-patients Fibromyalgia Clinic between May 2020 and December 2022 were asked to answer an online survey, including demographic characteristics, disease variables and the Italian version of the FIQR. Among the 544 patients that compiled the questionnaire, 78 patients, 39 males and 39 females matched for age and disease duration, were consecutively enrolled in order to compare their total FIQR score and the different domains scores. The univariate analysis of the FIQR scores, taking account of the total score and of the different domains of FIQR, showed that total scores and physical function domain scores were significantly higher in females compared to males. No significant differences emerged between the two groups regarding overall impact domain score and symptoms domain score. Among the 21 items of the FIQR, the female group obtained significantly higher scores answering the questions FIQR1 (brush or comb your hair), FIQR4 (vacuum, scrub, or sweep floors), FIQR5 (lift and carry a bag full of groceries), FIQR7 (change bed sheets), FIQR9 (go shopping for groceries) and FIQR21 (sensitivity to loud noises, bright lights, odors, cold). The results of our pilot study showed that female patients obtain significantly higher scores in the FIQR total score and in the physical function domain score, in particular in 5 out of the 9 sub-items of the FIQR physical function domain. These preliminary results indicate that the use of the FIQR as a severity index in male patients probably underestimates the disease impact in this group. In order to confirm these results the sample needs to be increased but it seems reasonable to conclude that the assessment of disease impact should be diversified, taking gender differences into account. [1]Marques A.P., Santo A.S.D.E, Berssaneti A.A., Matsutani L.A., Yuan S.L.K. Prevalence of fibromyalgia: literature review update. Rev Bras ReumatolEngl Ed.2017,57, 356-363. [2]Galvez-Sánchez C.M., Reyes Del Paso G.A. Diagnostic Criteria for Fibromyalgia: Critical Review and Future Perspectives. J Clin Med. 2020, 9, 1219. [3]Cabo-Meseguer A., Cerdá-Olmedo G., Trillo-Mata J.L. Fibromyalgia: Prevalence, epidemiologic profiles and economic costs. Med Clin (Barc).2017,149, 441-448. [3]Branco J.C., Bannwarth B., Failde I., AbelloCarbonell J., Blotman F., Spaeth M., Saraiva F., Nacci F., Thomas E., Caubère J.P., Le Lay K., Taieb C., Matucci-Cerinic M. Prevalence of fibromyalgia: a survey in five European countries. Semin Arthritis Rheum. 2010, 39, 448-53. NIL. None Declared. Table 1Significant differences in FIQR total, domains and single question scores based onsexScoreM (39)F (39)p-valueFIQR Total58.8 (23.5)70.3 (14.7).035FIQR Physicalfunction14.8 (8.2)20.1 (5.1).003FIQR1 Brush or comb your hair2.4 (3.3)4.3 (2.9).006FIQR4Vacuum, scrub, or sweep floors5.2 (3.6)7.5 (2.2).005FIQR5Lift and carry a bag full of groceries6.4 (3.1)8.3 (1.6).002FIQR7 Change bed sheets4.7 (3.6)7.1 (2.7).001FIQR9 Go shopping for groceries4.9 (3.3)6.7 (2.4).012FIQR21Sensitivity to loud noises, bright lights, odors, cold6.2 (2.7)7.9 (1.6).005

A case study of a 77-year-old right-handed functionally independent woman was presented to the emergency department about 12 hours after the acute onset of speech difficulties. The patient was a nonsmoker and was receiving treatment for hypercholesterolemia with a moderate dose of atorvastatin She had no other modifiable cerebrovascular risk factors and no personal history of cancer or thromboembolic events. Although a sibling had been diagnosed with colorectal cancer at age 65 years, the patient had never undergone any screening for colorectal cancer. On examination, she had mild aphasia and right pronator drift. A noncontrast head computed tomography (CT) scan showed an ischemic nonlacunar infarct of the superior and middle left temporal gyri. The patient was afebrile, and there was no evidence of infection on chest radiography or urinalysis. Following several tests, it has been ruled out that the patient has occult cancer.

Cervical and vaginal epithelia are primary barriers against HIV type I (HIV-1) entry during male-to-female transmission. Cervical mucus (CM) is produced by the endocervix and forms a layer locally as well as in the vaginal compartment in the form of cervicovaginal mucus (CVM). To study the potential barrier function of each mucus type during HIV-1 transmission, we quantified HIV-1 mobility in CM and CVM ex vivo using fluorescent microscopy. Virions and 200-nm PEGylated beads were digitally tracked and mean-squared displacement was calculated. The mobility of beads increased significantly in CVM compared with CM, consistent with the known decreased mucin concentration of CVM. Unexpectedly, HIV-1 diffusion was significantly hindered in the same CVM samples in which bead diffusion was unhindered. Inhibition of virus transport was envelope-independent. Our results reveal a previously unknown activity in CVM that is capable of impeding HIV-1 mobility to enhance mucosal barrier function.

BACKGROUND: In our study we used immunohistochemical technique to demonstrate the presence of the cytokines tumour necrosis factor alpha (TNF-α), interleukin 1beta (IL-1β), transforming growth factor beta1 (TGF-β1) and intercellular adhesion molecule-1 (ICAM-1) in porcine coronaries even in physiological conditions. MATERIALS AND METHODS: Inflammatory cytokines are polypeptide mediators which act as a communication signal between immune system cells and other types of cellsin different organs and tissues, both in human and pig coronary circulation. RESULTS: Our results show that pro-inflammatory cytokines TNF-α, IL-1β, TGF-β1 and ICAM-1 are also present in the medium tunica of the coronary arteries under physiological conditions. These results may be compared with those found in coronary atherosclerosis, where the increase in TNF-α has a dramatic effect on the function of the left ventricle, and the high value of IL-1 correlates directly with the extent of myocardial necrosis. In our study we observe the damage and activation of endothelial cells; this induces endothelial dysfunction by accumulation and oxidation of low density lipoproteins (LDL). The formation of oxidized LDL could play a central role in the amplification of the inflammatory response causing an increased expression of pro-inflammatory cytokines which promotes leukocyte recruitment in the intimal layer. These leukocytes, after the adhesion to the endothelium, penetrate the intimate tunic. CONCLUSIONS: Therefore inflammatory processes promote the onset and evolution of atheroma and the development of thrombotic complications.

Objective. To compare etanercept and adalimumab biosimilars (SB4 and ABP501) and respective bioriginators in terms of safety and efficacy in a real-life contest. Methods. We consequently enrolled patients affected by rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with SB4, and ABP501, or with corresponding originators, belonging to the main biological prescribing centers in the Lazio region (Italy), from 2017 to 2020. Data were collected at recruitment and after 4, 8, 12, and 24 months of therapy. Results. The multicenter cohort was composed by 455 patients treated with biosimilars [SB4/ABP501 276/179; female/male 307/146; biologic disease-modifying anti-rheumatic drug (b-DMARD) naïve 56%, median age/ interquartile range 55/46-65 years] and 436 treated with originators (etanercept/adalimumab 186/259, female/ male 279/157, b-DMARD naïve 67,2%, median age/interquartile range 53/43-62 years). No differences were found about safety, but the biosimilar group presented more discontinuations due to inefficacy (p<0.001). Female gender, being a smoker, and being b-DMARD naïve were predictive factors of reduced drug survival (p=0.05, p=0.046, p=0.001 respectively). The retention rate at 24 months was 81.1% for bioriginators and 76.5% for biosimilars (median retention time of 20.7 and 18.9 months, respectively) (p=0.002). Patients with remission/low disease activity achievement at 4 months showed a cumulative survival of 90% to biosimilar therapy until 24 months (p=0.001); early adverse reactions instead represented a cause of subsequent drug discontinuation (p=0.001). Conclusions. Real-life data demonstrated a similar safety profile between biosimilars and originators, but a reduced biosimilar retention rate at 24 months. Biosimilars could be considered a valid, safe, and less expensive alternative to originators, allowing access to treatments for a wider patient population.