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Intrauterine infection/inflammation (IUI) is a frequent complication of pregnancy leading to preterm labor and fetal infllammation. How inflammation is modulated at the maternal-fetal interface is unresolved. We compared transcriptomics of amnion (a fetal tissue in contact with amniotic fluid) in a preterm rhesus macaque model of IUI-induced by lypopolysaccharide with human cohorts of chorioamnionitis. Bulk RNA-seq amnion transcriptomic profiles were remarkably similar in both rhesus and human subjects and revealed that induction of key labor-mediating genes such as IL1 and IL6 was dependent on NF-kB signaling and reversed by the anti-TNF antibody Adalimumab. Inhibition of collagen biosynthesis by IUI was partially restored by Adalimumab. Interestingly, single-cell transcriptomics, flow cytometry, and immuno-histology demonstrated that a subset of amnion mesenchymal cells (AMCs) increase CD14 and other myeloid cell markers during IUI both in the human and Rhesus macaque. Our data suggest that CD14+ AMCs represent activated AMCs at the maternal-fetal interface.

The published online version contains mistake in the author list for the author “M. Cappelletti” was incorrectly presented.

Objectives: Canakinumab is an IL-1? antibody that neutralises the activity of IL-1?. This study examined the efficacy and safety of canakinumab in patients with moderate COVID-19-related pneumonia. Design: This study aimed to evaluate the reduction in duration of hospitalisation with adequate oxygen status. Forty-eight patients with moderate COVID-19-related pneumonia were asked to participate in the prospective case-control study: 33 patients (cases) signed informed consent and received canakinumab (Cohort 1) and 15 patients (Controls) refused to receive the experimental drug and received institutional standard of care (Cohort 2). Results: Hospital discharge within 21 days was seen in 63% of patients in Cohort 1 vs. 0% in Cohort 2 (median 14 vs. 26 days, respectively; p < 0.001). There was significant clinical improvement in ventilation regimes following administration of canakinumab compared with Cohort 2 (Stuart-Maxwell test for paired data, p < 0.001). Patients treated with canakinumab experienced a significant increase in PaO2: FiO2 (p < 0.001) and reduction in lung damage by CT (p = 0.01), along with significant decreases in immune/inflammation markers that were not observed in Cohort 2. Only mild side-effects were seen in patients treated with canakinumab; survival at 60 days was 90.0% (95% CI 71.9?96.7) in patients treated with canakinumab and 73.3% (95% CI 43.6?89.1) for Cohort 2. Conclusions: Treatment with canakinumab in patients with COVID-19-related pneumonia rapidly restored normal oxygen status, decreased the need for invasive mechanical ventilation, and was associated with earlier hospital discharge and favourable prognosis versus standard of care. ? 2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc

The heterogeneity of metastatic breast cancer (MBC) necessitates novel biomarkers allowing stratification of patients for treatment selection and drug development. We propose to use the prognostic utility of circulating tumor cells (CTCs) for stratification of patients with stage IV disease., SCOPUS: re.j, info:eu-repo/semantics/published

A xenobank of patient-derived (PDX) ovarian tumor samples has been established consisting of tumors with different sensitivity to cisplatin (DDP), from very responsive to resistant. As the DNA repair pathway is an important driver in tumor response to DDP, we analyzed the mRNA expression of 20 genes involved in the nucleotide excision repair, fanconi anemia, homologous recombination, base excision repair, mismatch repair and translesion repair pathways and the methylation patterns of some of these genes. We also investigated the correlation with the response to platinum-based therapy. The mRNA levels of the selected genes were evaluated by Real Time-PCR (RT-PCR) with ad hoc validated primers and gene promoter methylation by pyrosequencing. All the DNA repair genes were variably expressed in all 42 PDX samples analyzed, with no particular histotype-specific pattern of expression. In high-grade serous/endometrioid PDXs, the CDK12 mRNA expression levels positively correlated with the expression of TP53BP1, PALB2, XPF and POLB. High-grade serous/ endometrioid PDXs with TP53 mutations had significantly higher levels of POLQ, FANCD2, RAD51 and POLB than high-grade TP53 wild type PDXs. The mRNA levels of CDK12, PALB2 and XPF inversely associated with the in vivo DDP antitumor activity; higher CDK12 mRNA levels were associated with a higher recurrence rate in ovarian patients with low residual tumor. These data support the important role of CDK12 in the response to a platinum based therapy in ovarian patients.

Il presente lavoro di ricerca riguarda principalmente i presupposti e le funzioni della c.d. tutela inibitoria prevista dal legislatore, conosciuta anche come injunction negli ordinamenti di common law. Occorre ricordare come nell’ordinamento italiano l’inibitoria individuale sia regolata da differenti norme del codice civile e della legislazione speciale, senza tuttavia trovare riscontro in una disciplina generale per i casi di violazioni continue e ripetute. Per questo motivo la natura dell’istituto – con specifico riferimento alla qualificazione giuridica e alla sua ammissibilità in via generale – è stata a lungo discussa nella dottrina, che ha considerato il rimedio come un’azione di condanna, di accertamento, costitutiva, ovvero come un quartumgenus. Tale situazione probabilmente muterà dal momento che nel giugno 2015 la Camera dei Deputati ha trasmesso al Senato il Disegno di Legge 1950 che da un lato sostituisce l’intero art. 140 del Codice del Consumo (relativo alla tutela inibitoria collettiva dei consumatori) e, dall’altro lato, trasferisce tale previsione all’interno del codice di procedura civile. Tale normativa (che è ancora soggetta all’approvazione finale del Senato), non solo è volta a rafforzare la rilevanza del rimedio inibitorio, ma è destinata a fondare nuove interpretazioni di dottrina e giurisprudenza, sebbene il DDL sia limitato alla dimensione collettiva. Alla luce di tali premesse ho tentato di analizzare le principali caratteristiche della tutela inibitoria, tenendo in considerazione sia la sua “direzione verso il futuro”, che il suo scopo preventivo, che la differenziano chiaramente dal dagli altri rimedi processuali. In tali casi, infatti, viene richiesto al giudice di ordinare l’interruzione e l’inibizione di qualsivoglia comportamento che sia pregiudizievole per l’attore. A tal fine, si sono anzitutto analizzate le previsioni legislative che disciplinano i differenti tipi di inibitoria – tra gli altri, l’art. 844 c.c. (immissioni, The subject matter of this work deals with both the requirements and functions of the s.c. “inhibitory” protection provided by our national legislator, also known as “injunction” within the Common law systems. It is important to recall that while the “inhibitory” protection has been somehow regulated by many different rules of the Civil code (and the special legislation as well), the Italian legal system has always been particularly reluctant in providing a general “inhibitorial” action against continuous and repetitive offenses. That is why the nature of the tool - with special reference to the juridical qualification and its general admissibility – has long been discussed among scholars, who treated the remedy as an action for declaration or an action for a relief, or even as a stand-alone legal instrument. The above mentioned situation is going to change, since in June 2015 the Italian House of Representatives passed a draft-law (d.d.l. n. 1950) which, among other things, on the one hand repeals the entire article nr. 140 of the s.c. Consumer Code (devoted to the collective “inhibitory” protection for consumers) and, on the other hand, set a new disposition, providing the same legal protection, within our Civil procedural code. Such provision (which is still subject to the final Senate confirmation), not only is expected to enhance the relevance of the “inhibitory” remedy, but it will likely soon establish a new set of legal interpretations within the case law as well as among academics, even though the draft is limited to the collective inhibitory protection only. Therefore I tried to face and investigate the main features of the “inhibitory” protection, taking into account both its “direction to the future” and its preventive goal, which clearly make the difference compared to the other jurisdictional means. In such cases, in fact, the judge is requested to order the interruption and the inhibition of any unlawful and detrimental behaviors against the claimant.

We conducted a meta-analysis in nonmetastatic breast cancer patients treated by neoadjuvant chemotherapy (NCT) to assess the clinical validity of circulating tumor cell (CTC) detection as a prognostic marker., SCOPUS: ar.j, info:eu-repo/semantics/published