COVID-19 vaccination campaigns and the production of mistrust among Roma and migrant populations in Italy

Achieving high rates of COVID-19 vaccination has become central to a return to normalcy in a post-pandemic world. Accordingly, exceptional measures, such as the regulation of immunity through vaccine passports and restrictions that distinguished between vaccinated and unvaccinated individuals, became a feature of vaccination campaigns in certain G7 countries. Such policies stand in tension with recent supranational European Union policies that seek to build inclusion and trust through engaging minoritised groups in vaccine campaigns. To explore this tension, we present novel ethnographic data produced with migrant and Roma communities in Italy. Our evidence suggests that under restrictive measures, many within these groups initially described as 'vaccine hesitant' have accepted a vaccine. Yet, rather than indicating successful civic engagement, we find that vaccine acceptance was tied to deepening mistrust in science and the state. Considering the structural socioeconomic, historical and cultural elements informing people's vaccination choices, we propose a shift in emphasis towards equitable principles of engagement

Prescription Appropriateness of Drugs for Peptic Ulcer and Gastro-Esophageal Reflux Disease: Baseline Assessment in the LAPTOP-PPI Cluster Randomized Trial

Background: Drugs for peptic ulcer and gastro-esophageal reflux disease (GERD) are among the most widely prescribed, frequently without appropriate indications. This represents an important issue, as it leads to risk of adverse events for patients and unnecessary costs for National Health Service. Aim: To assess the prescription appropriateness of drugs for GERD, in the frame of the "Evaluation of the effectiveness of a Low-cost informative intervention to improve the Appropriate PrescripTiOn of Proton PumP Inhibitors in older people in primary care: a cluster-randomized controlled study" (LAPTOP-PPI) (Clinicaltrial.gov: NCT04637750). Methods: The appropriateness of drug prescription was assessed on data collected in administrative databases, by integrating information on concomitant medications, outpatient medical and laboratory procedures and hospital discharge diagnoses, according to the reimbursement criteria provided by the Italian Medicine Agency. We analyzed data of community-dwelling people aged 65 years and over, living in the areas of Bergamo (Northern Italy) and Caserta (Southern Italy), from July 1 to 31 December 2019. Results: Among 380,218 patients, 175,342 (46.1%) received at least one prescription of drugs for GERD. All in all, we found that only 41.2% of patients received appropriate prescriptions. Conclusion: Given the potential risk of adverse drug reactions, especially in older people, educational interventions should be prompted for physicians, in order to improve the quality of prescription of drugs for GERD and, in turn, avoid unfavorable health outcomes and unnecessary costs

Butyrylcholinesterase and Acetylcholinesterase polymorphisms in Multiple Sclerosis patients: Implication in peripheral inflammation

Multiple Sclerosis (MS) is an autoimmune disease, having not fully understood aetiology, and both genetic and environmental factors contribute to the pathogenesis of the disease. The cholinergic system has been indicated as a mediator of neuro-immune interactions, as well as an internal regulator of immune responses. The aim of the present research was to assess the associations between BChE and AChE genetic variations and serum cholinergic and inflammatory profiles in 102 Relapsing Remitting-MS patients and 117 healthy controls. An increased frequency of the BChE K-allele in MS patients as compared to controls was found. In addition, data showed that patients had higher BChE enzymatic activity, which is increased by the presence of the polymorphic allele and reduced amounts of circulating ACh. AChE polymorphism was significantly associated to reduced activity in both patients and controls. We propose that serum BChE and AChE activity may be used as a secondary markers to assess the role of non-neuronal cholinergic system in regulating peripheral inflammation via ACh regulation. This pilot study shed light on the role of the non-neuronal cholinergic system in immune cells to better understand MS pathogenesis. The cross-talk between the periphery and the CNS could have a new undescribed crucial role for MS, regarded as a systemic disease

An asteroidal origin for water in the Moon

The Apollo-derived tenet of an anhydrous Moon has been contested following measurement of water in several lunar samples that require water to be present in the lunar interior. However, significant uncertainties exist regarding the flux, sources and timing of water delivery to the Moon. Here we address those fundamental issues by constraining the mass of water accreted to the Moon and modelling the relative proportions of asteroidal and cometary sources for water that are consistent with measured isotopic compositions of lunar samples. We determine that a combination of carbonaceous chondrite-type materials were responsible for the majority of water (and nitrogen) delivered to the Earth–Moon system. Crucially, we conclude that comets containing water enriched in deuterium contributed significantly <20% of the water in the Moon. Therefore, our work places important constraints on the types of objects impacting the Moon ~4.5–4.3 billion years ago and on the origin of water in the inner Solar System

La ponctuation et les reprises de l’indicible

Marque d’un manque à référer, l’indicible procède de la même manière que la métaphore. Or certains modes d’actions de la ponctuation sur le référé, que l’on analysera comme un processus de non congruence, autorisent à les identifier comme une forme de l’indicible. Cette contribution cherche à en analyser les modalités dans l’innomable de S. Beckett.The unsayable, as a mark of impossibility to refer, proceeds in the same way as a metaphor. Certain effects of ponctuation on the referent, which are analysed as a process of incongruence, allow us to identify them as a form of unutterability. This paper attempts to analyse these types of modality in Beckett’s L’innommable

Patient-derived explants of colorectal cancer: histopathological and molecular analysis of long-term cultures

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Colorectal cancer (CRC) is one of the most common cancers worldwide. Although short-term cultures of tumour sections and xenotransplants have been used to determine drug efficacy, the results frequently fail to confer clinically useful information. Biomarker discovery has changed the paradigm for advanced CRC, though the presence of a biomarker does not necessarily translate into therapeutic success. To improve clinical outcomes, translational models predictive of drug response are needed. We describe a simple method for the fast establishment of CRC patient-derived explant (CRC-PDE) cultures from different carcinogenesis pathways, employing agitation-based platforms. A total of 26 CRC-PDE were established and a subset was evaluated for viability (n = 23), morphology and genetic key alterations (n = 21). CRC-PDE retained partial tumor glandular architecture and microenvironment features were partially lost over 4 weeks of culture. Key proteins (p53 and Mismatch repair) and oncogenic driver mutations of the original tumours were sustained throughout the culture. Drug challenge (n = 5) revealed differential drug response from distinct CRC-PDE cases. These findings suggest an adequate representation of the original tumour and highlight the importance of detailed model characterisation. The preservation of key aspects of the CRC microenvironment and genetics supports CRC-PDE potential applicability in pre- and co-clinical settings, as long as temporal dynamics are considered.This research was supported by AbbVie and by iNOVA4Health—UIDB/04462/2020, a program financially supported by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Educação e Ciência, through national funds. TFM and SA were recipients of individual PhD fellowships funded by FCT (PD/BD/128377/2017 and PD/BD/105768/2014, respectively). CB acknowledges the support from “The Discoveries Centre for Regenerative and Precision Medicine” (European Commission Horizon 2020 Research and Innovation programme, under the Grant Agreement number 739572).info:eu-repo/semantics/publishedVersio

Dabigatran-induced acute liver injury in older patients: case report and literature review

Objective. Dabigatran, a direct inhibitor of thrombin, represents an effective alternative to warfarin. Despite the good tolerance and predictable pharmacokinetic profile, dabigatran may be associated to adverse reactions, including gastrointestinal disorders. Here we report on a case of hepatotoxicity along with an extensive revision of the available literature on dabigatran induced liver injury Methods & results. An 84 years old man attended the Emergency Department after experiencing fatigue for a few days. He suffered from atrial fibrillation and had been initiated on dabigatran (110 mg bid) in the last four weeks. Clinical examination revealed tachycardia, scleral icterus in the absence of signs of chronic hepatic disease. Blood chemistry showed altered liver function tests: AST 809 IU/L, ALT 1629 IU/L, total bilirubin 2.42 mg/dL, gGT 381 IU/L, ALP 388 IU/L, LDH 552 IU/L. Screening laboratory investigations for infectious, autoimmune or metabolic hepatotoxic pathology were unremarkable. The abdominal ultrasound examination excluded vascular causes, revealing non-homogeneous echo-structure consistent with mild hepatic steatosis. At admission to our Geriatric ward dabigatran was discontinued and fondaparinux was introduced. Resolution of the hepatitis and normalization of blood chemistry was observed within two weeks. Few cases are described regarding hepatotoxicity likely caused by the recent onset of treatment with dabigatran. Conclusions. DOACs associated hepatotoxicity is rare but potentially harmful and should be kept in mind, especially in comorbid patients with unexplained liver injury. The mechanism of liver injury during dabigatran therapy is unknown and, not related to cytochrome P450 enzymes since the drug does not affect CYP450 activity

Gamma-hydroxybutyrate does not maintain self-administration but induces conditioned place preference when injected in the ventral tegmental area

Gamma-hydroxybutyric acid (GHB) is an endogenous brain substance that has diverse neuropharmacological actions, including rewarding properties in different animal species and in humans. As other drugs of abuse, GHB affects the firing of ventral tegmental neurons (VTA) in anaesthetized animals and hyperpolarizes dopaminergic neurons in VTA slices. However, no direct behavioural data on the effects of GHB applied in the VTA or in the target regions of its dopaminergic neurons, e.g. the nucleus accumbens (NAc), are available. Here, we investigated the effects of various doses of intravenous GHB in maintaining self-administration (from 0.001 to 10 mg/kg per infusion), and its ability to induce conditioned place preference (CPP) in rats when given orally (175-350 mg/kg) or injected directly either in the VTA or NAc (from 10 to 300 microg/0.5 microl per side). Our results indicate that while only 0.01 mg/kg per infusion GHB maintained self-administration, although not on every test day, 350 mg/kg GHB given orally induced CPP. CPP was also observed when GHB was injected in the VTA (30-100 microg/0.5 microl per side) but not in the NAc. Together with recent in-vitro findings, these results suggest that the rewarding properties of GHB mainly occur via disinhibition of VTA dopaminergic neurons