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Purpose To assess Crohn’s disease (CD) activity through analysis of time–signal intensity curves and quantitative contrast-enhancement parameters on dynamic contrast-enhanced MRI. Materials and methods 70 patients (male:female = 44:26, age 15–45 years, mean 27.8 years) with biopsy-proven clinically active or inactive CD, underwent dynamic contrast-enhanced MRI after oral administration of iso-osmotic solution. Time–signal intensity curves were classified according to their shape as type I (early upslope with late plateau) and type II (slow contrast material wash-in with late wash-out). Curve parameters such as maximum enhancement (ME), the ratio between late and ME (LE/ME), and UpSlope (US) were compared between patients with active and inactive CD (two-tailed Mann–Whitney test). Sensitivity, specificity, and cut-off for each parameter were calculated by means of receiver operating characteristic curve (ROC) analysis. Results 53/53 patients with active CD and 17/17 with inactive CD showed type I and type II curves, respectively. ME, LE/ME, and US were significantly higher in active than in inactive CD. ME, LE/ME, and US had sensitivity and specificity of 100%:100%:100% and 100%:83%:100% with cut-offs of 135.5:0.8909:2, respectively. Conclusions Qualitative and quantitative analysis of time–signal intensity curves obtained with dynamic contrast-enhanced MRI allow reliable noninvasive differentiation between active and inactive CD.

The crosstalk between the chromaffin and adrenocortical cells is essential for the endocrine activity of the adrenal glands. This interaction is also likely important for tumorigenesis and progression of adrenocortical cancer and pheochromocytoma. We developed a unique in vitro 3D model of the whole adrenal gland called Adrenoid consisting in adrenocortical carcinoma H295R and pheochromocytoma MTT cell lines. Adrenoids showed a round compact morphology with a growth rate significantly higher compared to MTT-spheroids. Confocal analysis of differential fluorescence staining of H295R and MTT cells demonstrated that H295R organized into small clusters inside Adrenoids dispersed in a core of MTT cells. Transmission electron microscopy confirmed the strict cell–cell interaction occurring between H295R and MTT cells in Adrenoids, which displayed ultrastructural features of more functional cells compared to the single cell type monolayer cultures. Adrenoid maintenance of the dual endocrine activity was demonstrated by the expression not only of cortical and chromaffin markers (steroidogenic factor 1, and chromogranin) but also by protein detection of the main enzymes involved in steroidogenesis (steroidogenic acute regulatory protein, and CYP11B1) and in catecholamine production (tyrosine hydroxylase and phenylethanolamine N-methyltransferase). Mass spectrometry detection of steroid hormones and liquid chromatography measurement of catecholamines confirmed Adrenoid functional activity. In conclusion, Adrenoids represent an innovative in vitro 3D-model that mimics the spatial and functional complexity of the adrenal gland, thus being a useful tool to investigate the crosstalk between the two endocrine components in the pathophysiology of this endocrine organ.

Plasma-derived therapeutic proteins are produced through an industrial fractionation process where proteins are purified from individual intermediates, some of which remain unused and are discarded. Relatively few plasma-derived proteins are exploited clinically, with most of available plasma being directed towards the manufacture of immunoglobulin and albumin. Although the plasma proteome provides opportunities to develop novel protein replacement therapies, particularly for rare diseases, the high cost of plasma together with small patient populations impact negatively on the development of plasma-derived orphan drugs. Enabling therapeutics development from unused plasma fractionation intermediates would therefore constitute a substantial innovation. To this objective, we characterized the proteome of unused plasma fractionation intermediates and prioritized proteins for their potential as new candidate therapies for human disease. We selected ceruloplasmin, a plasma ferroxidase, as a potential therapy for aceruloplasminemia, an adult-onset ultra-rare neurological disease caused by iron accumulation as a result of ceruloplasmin mutations. Intraperitoneally administered ceruloplasmin, purified from an unused plasma fractionation intermediate, was able to prevent neurological, hepatic and hematological phenotypes in ceruloplasmin-deficient mice. These data demonstrate the feasibility of transforming industrial waste plasma fraction into a raw material for manufacturing of new candidate proteins for replacement therapies, optimizing plasma use and reducing waste generation. Proteomics of waste intermediates from industrial plasma fractionation samples revealed new candidate therapeutic proteins such as ceruloplasmin, which reverted central nervous system and peripheral deficits in ceruloplasmin-deficient mice.

Background We evaluated LGV prevalence and predictors in a high risk population attending a STI Outpatients Clinic in the North of Italy. Methods A total of 108 patients (99 MSM and 9 women), with a history of unsafe anal sexual intercourses, were enrolled. Anorectal swabs and urine samples were tested for Chlamydia trachomatis (CT) DNA detection by Versant CT/GC DNA 1.0 Assay (Siemens Healthcare Diagnostics Terrytown, USA). RFLP analysis was used for CT molecular typing. Results L2 CT genotype was identified in 13/108 (12%) rectal swabs. All LGV cases were from MSM, declaring high-risk sexual behaviour and complaining anorectal symptoms. Patients first attending the STI Outpatient Clinic received a significant earlier LGV diagnosis than those first seeking care from general practitioners or gastroenterologists ( P  = 0.0046). LGV prevalence and characteristics found in our population are in agreement with international reports. Statistical analysis showed that LGV positive patients were older ( P  = 0.0008) and presented more STIs (P  = 0.0023) than LGV negative ones, in particular due to syphilis (P  < 0.001), HIV ( P  < 0.001) and HBV ( P  = 0.001). Multivariate logistic regression analysis revealed that HIV and syphilis infections are strong risk factors for LGV presence (respectively, P  = 0.001 and P  = 0.010). Conclusions Even if our results do not provide sufficient evidence to recommend routine screening of anorectal swabs in high-risk population, they strongly suggest to perform CT NAAT tests and genotyping on rectal specimens in presence of ulcerative proctitis in HIV and/or syphilis-positive MSM. In this context, CT DNA detection by Versant CT/GC DNA 1.0 Assay, followed by RFLP analysis for molecular typing demonstrated to be an excellent diagnostic algorithm for LGV identification.

A loggerhead sea turtle (Caretta caretta) was found stranded alive along the Adriatic coast close to Ancona, Italy, displaying obtundation, tachypnea, and increased respiratory effort. It died a few hours after admission, and a postmortem examination was immediately performed. Miliary yellowish nodules were evident in the liver, and a lower number in the heart, stomach, and gut wall. Hundreds of whitish nodules were scattered in the lungs, with the majority of the pulmonary parenchyma being replaced by the lesions. Histologically, all nodular lesions consisted of a small central area of necrosis with acid-fast bacilli surrounded by epithelioid cells, macrophages, and lymphocytes. Giant cells were found in the spleen and the liver. Kidneys, lungs, liver, spleen, brain, and skin lesions were inoculated aseptically onto general isolation media and selective isolation media for mycobacteria. The isolate showed a restriction pattern identical to Mycobacterium chelonae by polymerase chain reaction–restriction fragment length polymorphism. To the best of the authors' knowledge, this is the first description of a disseminated infection caused by a potentially pathogenic mycobacteria in a stranded, free-ranging loggerhead sea turtle. Veterinary staff and biologists who handle sea turtles with suspected mycobacterial disease should protect themselves appropriately.

►Aim. The aim of the study was to identify children at risk of neurodevelopmental disorders through the use of validated instruments by family paediatricians and parents.►Methods. As part of the NASCITA cohort study, the development of 148 children was evaluated. Family pediatricians (FPs) conducted assessments using the CDC Learn the Signs, Act Early Milestones Checklist, while parents completed the Strengths and Difficulties Questionnaire (SDQ). Children were considered at risk if their total score was ≥ 12 on the CDC or > 14 on the SDQ. Univariate and multivariate analyses were performed to assess which variables were associated with a higher likelihood of warning signs (WS).►Results. In all, 14% of children showed WS for developmental disorders at 36 months, a lower percentage than the 24-month assessment (16%): for two out of three children, WS disappeared between 24 and 36 months of age. Persistent WS were observed in 5% of children. Key risk factors identified include older maternal age at delivery (OR 8.93, 95% CI: 1.87 - 42.62) and maternal unemployment (OR 4.75, 95% CI: 1.40 - 16.09), while reading aloud emerged as a protective practice, emphasizing its potential in early interventions.►Conclusions. These results highlight the need for continuous monitoring of WS and the importance of positive parental practices in mitigating developmental risks. Early identification by primary care pediatricians is crucial in addressing developmental concerns early and improving long-term outcomes.