Thymus vulgaris Essential Oil in Beta-Cyclodextrin for Solid-State Pharmaceutical Applications

: Antimicrobial resistance related to the misuse of antibiotics is a well-known current topic. Their excessive use in several fields has led to enormous selective pressure on pathogenic and commensal bacteria, driving the evolution of antimicrobial resistance genes with severe impacts on human health. Among all the possible strategies, a viable one could be the development of medical features that employ essential oils (EOs), complex natural mixtures extracted from different plant organs, rich in organic compounds showing, among others, antiseptic properties. In this work, green extracted essential oil of Thymus vulgaris was included in cyclic oligosaccharides cyclodextrins (CD) and prepared in the form of tablets. This essential oil has been shown to have a strong transversal efficacy both as an antifungal and as an antibacterial agent. Its inclusion allows its effective use because an extension of the exposure time to the active compounds is obtained and, therefore, a more marked efficacy, especially against biofilm-producing microorganisms such as P. aeruginosa and S. aureus, was registered. The efficacy of the tablet against candidiasis opens their possible use as a chewable tablet against oral candidiasis and as a vaginal tablet against vaginal candidiasis. Moreover, the registered wide efficacy is even more positive since the proposed approach can be defined as effective, safe, and green. In fact, the natural mixture of the essential oil is produced by the steam current method; therefore, the manufacturer employs substances that are not harmful, with very low production and management costs

Reduced humoral response to two doses of COVID-19 vaccine in patients with inflammatory bowel disease: Data from ESCAPE-IBD, an IG-IBD study

Background Patients on immunosuppressive drugs have been excluded from COVID-19 vaccines trials, creating concerns regarding their efficacy. Aims To explore the humoral response to COVID-19 vaccines in patients with inflammatory bowel disease (IBD) Methods Effectiveness and Safety of COVID-19 Vaccine in Patients with Inflammatory Bowel Disease (IBD) Treated with Immunomodulatory or Biological Drugs (ESCAPE-IBD) is a prospective, multicentre study promoted by the Italian Group for the study of Inflammatory Bowel Disease. We present data on serological response eight weeks after the second dose of COVID-19 vaccination in IBD patients and healthy controls (HCs). Results 1076 patients with IBD and 1126 HCs were analyzed. Seropositivity for anti-SARS-CoV-2 IgG was reported for most IBD patients, even if with a lesser rate compared with HCs (92.1% vs. 97.9%; p<0.001). HCs had higher antibody concentrations (median OD 8.72 [IQR 5.2-14-2]) compared to the whole cohort of IBD patients (median OD 1.54 [IQR 0.8-3.6]; p<0.001) and the subgroup of IBD patients (n=280) without any treatment or on aminosalicylates only (median OD 1.72 [IQR 1.0–4.1]; p<0.001). Conclusions Although most IBD patients showed seropositivity after COVID-19 vaccines, the magnitude of the humoral response was significantly lower than in HCs. Differently from other studies, these findings seem to be mostly unrelated to the use of immune-modifying treatments (ClinicalTrials.govID:NCT04769258)

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Small Bowel Metastatic Melanoma: An Emblematic &ldquo;Coal-Black&rdquo; Appearance at Videocapsule Endoscopy

A 80-year-old woman underwent vulvar melanoma resection and segmental lung resection for pulmonary metastasis. Immunotherapy with Nivolumab was performed. One year later, the patient was admitted for gastrointestinal (GI) recurrent bleeding and severe anemia. Esophagoastroduodenoscopy and colonoscopy did not show any abnormality, while videocapsule endoscopy (VCE) revealed an irregular and exophytic whitish area with a &ldquo;coal-black&rdquo; central depression. Small bowel resection was performed and histological examination revealed S100 protein strongly positive melanoma metastasis. The patient died six months later from disease progression. A &ldquo;coal-black&rdquo; appearance of intestinal metastatic melanoma has been described only twice before this report. In one case the patient had been treated by immunotherapy with interferon A and dendritic cell-based vaccination. In our patient, it is presumable that the picture we observed was a consequence of Nivolumab treatment inducing the disappearance of melanocytes in the area surrounding the metastasis with the onset of the central coal-black lesion encircled by whitish tissue. This picture should be emblematic of intestinal metastatic melanoma in subjects treated with immunotherapy showing occult/obscure bleeding

Drosophila melanogaster as a model to study autophagy in neurodegenerative diseases induced by proteinopathies

Proteinopathies are a large group of neurodegenerative diseases caused by both genetic and sporadic mutations in particular genes which can lead to alterations of the protein structure and to the formation of aggregates, especially toxic for neurons. Autophagy is a key mechanism for clearing those aggregates and its function has been strongly associated with the ubiquitin-proteasome system (UPS), hence mutations in both pathways have been associated with the onset of neurodegenerative diseases, particularly those induced by protein misfolding and accumulation of aggregates. Many crucial discoveries regarding the molecular and cellular events underlying the role of autophagy in these diseases have come from studies using Drosophila models. Indeed, despite the physiological and morphological differences between the fly and the human brain, most of the biochemical and molecular aspects regulating protein homeostasis, including autophagy, are conserved between the two species.In this review, we will provide an overview of the most common neurodegenerative proteinopathies, which include PolyQ diseases (Huntington’s disease, Spinocerebellar ataxia 1, 2, and 3), Amyotrophic Lateral Sclerosis (C9orf72, SOD1, TDP-43, FUS), Alzheimer’s disease (APP, Tau) Parkinson’s disease (a-syn, parkin and PINK1, LRRK2) and prion diseases, highlighting the studies using Drosophila that have contributed to understanding the conserved mechanisms and elucidating the role of autophagy in these diseases

Small Bowel Metastatic Melanoma: An Emblematic "Coal-Black" Appearance at Videocapsule Endoscopy

A 80-year-old woman underwent vulvar melanoma resection and segmental lung resection for pulmonary metastasis. Immunotherapy with Nivolumab was performed. One year later, the patient was admitted for gastrointestinal (GI) recurrent bleeding and severe anemia. Esophagoastroduodenoscopy and colonoscopy did not show any abnormality, while videocapsule endoscopy (VCE) revealed an irregular and exophytic whitish area with a "coal-black" central depression. Small bowel resection was performed and histological examination revealed S100 protein strongly positive melanoma metastasis. The patient died six months later from disease progression. A "coal-black" appearance of intestinal metastatic melanoma has been described only twice before this report. In one case the patient had been treated by immunotherapy with interferon A and dendritic cell-based vaccination. In our patient, it is presumable that the picture we observed was a consequence of Nivolumab treatment inducing the disappearance of melanocytes in the area surrounding the metastasis with the onset of the central coal-black lesion encircled by whitish tissue. This picture should be emblematic of intestinal metastatic melanoma in subjects treated with immunotherapy showing occult/obscure bleeding

Human Leukocyte Antigen (HLA) Haplotype Does Not Influence the Inflammatory Pattern of Duodenal Lymphocytosis Linked to Irritable Bowel Syndrome

Background and objectives: Duodenal lymphocytosis (DL) is a condition characterized by enhanced infiltration of intraepithelial lymphocytes (IELs) in the duodenal mucosa, and it can be linked to both gluten- and non-gluten-related diseases, such as irritable bowel syndrome (IBS). Materials and methods: We retrospectively selected patients with DL linked to IBS. Formalin-embedded biopsy samples of the duodenum were collected. CD3 lymphocyte immunohistochemistry was used for IELs. The real-time polymerase chain reaction was used to quantify the amount of mRNA coding for tissue transglutaminase 2 (tTG2), interferon-gamma (IFN&gamma;), toll-like receptor 2 (TLR2), and myeloid differentiation primary response 88 (MyD88). All subjects underwent DQ2-8 haplotype analysis. Controls were represented by subjects with IBS without DL. Results: Thirty-two patients with IBS-DL were retrospectively recruited. Fourteen subjects (43.8%) had a DQ2-8 haplotype. DQ2-8 positive subjects had similar levels compared to negative ones for tTG2, IFN&gamma;, TLR2, and MyD88. Cigarette smoke did not influence molecular expression in our study. Smokers had a statistically higher IELs count than non-smokers (54.2 &plusmn; 7.7 vs. 36.0 &plusmn; 8.8, p &lt; 0.001). A significant, direct correlation between IELs and duodenal expression of IFN&gamma; was found (r = 0.36, p = 0.04). Conclusions: IBS with DL showed higher expression of inflammatory markers than controls, but DQ2-8 haplotype did not seem to affect their expression. Smoking might increase IELs infiltration

Promuovere corresponsabilita\u300 Servizi educativi-famiglia

L\u2019articolo presentato vuole mettere in evidenza come la corresponsabilita\u300 educativa tra genitori ed educatori dei Servizi 0-6 sia fondamentale per la crea- zione di un\u2019autentica comunita\u300 educante che ha lo scopo di sostenere bambine e bambini in una crescita integrata. La corresponsabilita\u300 non si configura ne\u301 come punto di partenza ne\u301 come traguardo definitivo, quanto come una ten- sione, un assetto precario, fragile ma importantissimo, in cui il dialogo, l\u2019ascolto delle storie reciproche, la partecipazione si fondono e intrecciano per far si\u300 che un modello pedagogico realmente inclusivo si realizzi

Female reproductive health and inflammatory bowel disease: A practice-based review

Inflammatory bowel diseases, namely ulcerative colitis and Crohn's disease, occur worldwide and affect people of all ages, with a high impact on their quality of life. Sex differences in incidence and prevalence have been reported, and there are also gender-specific issues that physicians should recognize. For women, there are multiple, important concerns regarding issues of body image and sexuality, menstruation, contraception, fertility, pregnancy, breastfeeding and menopause. This practice-based review focuses on the main themes that run through the life of women with inflammatory bowel diseases from puberty to menopause. Gastroenterologists who specialize in inflammatory bowel diseases and other physicians who see female patients with inflammatory bowel diseases should provide support for these problems and offer adequate therapy to ensure that their patients achieve the same overall well-being and health as do women without inflammatory bowel diseases. (c) 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved

Phase II study of eribulin in combination with gemcitabine for the treatment of patients with locally advanced or metastatic triple negative breast cancer: ERIGE trial on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC).

Background: There are no well-established chemotherapy regimens for metastatic triple negative breast cancer. The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, especially in tumors like triple negative breast cancers (TNBC) characterized by high cell proliferation, aggressive tumor behavior, and chemo-resistance. Methods: We performed an open-label, national multicenter phase 2 study evaluating the combination of eribulin (0.88 mg/m2) plus gemcitabine (1000 mg/m2) on day 1 and 8, q21 as either first- or second-line treatment of locally advanced or metastatic TNBC. The Simon's optimal two-stage design was used for estimating objective response rate (ORR) as study primary endpoint. A prospective, molecular correlative study was carried out on germinal DNA of study population to assess the role of germinal DNA polymorphisms and BRCA mutations in predicting efficacy and toxicity of the combination regimen. Results: From July 2013 to September 2016, 83 (37 in the first stage, 46 in the second one) assessable patients were enrolled. Median age at baseline was 56 years. Sixty-six and 17 patients were in first or second-line treatment, respectively. All patients were previously treated with an anthracycline and/or a taxane. With regard to the first stage of study enrolment, patients received a median number of 6 cycles of treatment. The ORR (CR+PR) was 43.24% (90% CI 29.3-58.0) and the clinical benefit rate (CR+PR+SD) was 64.9% (90% CI: 50.1%-77.8%). The most common grade 3/4 AEs ( > 10% of patients) were neutropenia without febrile neutropenia and liver toxicity. Grade 1/2 AEs were fatigue, anemia, thrombocytopenia, diarrhea, alopecia, peripheral neuropathy, and oral mucositis. Conclusions: The combination of eribulin and gemcitabine shows promising activity and a moderate toxicity profile in metastatic TNBC. More mature toxicity and outcome data of the final study population and correlation with genome analysis will be presented at the meeting. Clinical trial information: 2012-003505-10