Association between benzodiazepine prescriptions and potential risk factors of adverse drug reactions among elderly and very elderly: Findings from Friuli Venezia Giulia region, Italy

4noBackground: benzodiazepines (BDZs) highly increase the risk of adverse drug reactions (ADRs), especially in the elderly with certain medical conditions. Methods: point-prevalence study in December 2017; 2,456 patients ≥65 years were included from 14 regional public and private hospitals, 24 long-term chronic care facilities (LTCCFs) and 20 nursing homes (NHs). Data regarded BDZ prescriptions and comorbidities, co-prescriptions, or concurrent diseases, which could increase the risk of ADRs in BDZ users. Univariate and multivariate logistic regression analyses were used to assess associations between ADRs in BDZ users vs. non-users, as well as within users. Results: 671 patients were prescribed BDZ, whose half were in NHs. Being prescribed 10 or more drugs was twice more common among BDZ users compared to non-users. BDZs were prescribed for long-term to 80% of patients in NHs, while proportions were halved in hospitals and LTCCFs. In the analyses within BDZ users, patients in NHs and LTCCFs were at higher risk of dementia and concurrent use of opioid analgesic and antipsychotics compared to hospitalized patients. Conclusions: the use of BDZs in older patients is common in FVG. A great extent of comorbidities and concurrent medications at higher risk of ADRs was found. Analyses in different healthcare settings can allow to drive evidence-based interventions in order to discourage the use of BDZs and monitor the raise of ADRs.nonenoneCastelpietra G.; Balestrieri M.; Brusaferro S.; Arnoldo L.Castelpietra, G.; Balestrieri, M.; Brusaferro, S.; Arnoldo, L

Combining electrostatic, hindrance and diffusive effects for predicting particle transport and separation efficiency in deterministic lateral displacement microfluidic devices

Microfluidic separators based on Deterministic Lateral Displacement (DLD) constitute a promising technique for the label-free detection and separation of mesoscopic objects of biological interest, ranging from cells to exosomes. Owing to the simultaneous presence of different forces contributing to particle motion, a feasible theoretical approach for interpreting and anticipating the performance of DLD devices is yet to be developed. By combining the results of a recent study on electrostatic effects in DLD devices with an advection-diffusion model previously developed by our group, we here propose a fully predictive approach (i.e., ideally devoid of adjustable parameters) that includes the main physically relevant effects governing particle transport on the one hand, and that is amenable to numerical treatment at affordable computational expenses on the other. The approach proposed, based on ensemble statistics of stochastic particle trajectories, is validated by comparing/contrasting model predictions to available experimental data encompassing different particle dimensions. The comparison suggests that at low/moderate values of the flowrate the approach can yield an accurate prediction of the separation performance, thus making it a promising tool for designing device geometries and operating conditions in nanoscale applications of the DLD technique

Neuroimaging, Networking and Systems Biology: The New Way to Investigate Pathologies with Neurological System Implications. The example of Tourette Syndrome as a Pilot Study

Purpose: Recently, many academic research groups have focused their attention on changes in human brain networks related to several kinds of pathologies and diseases, generating the new discipline termed “Network Medicine”. Purpose of this paper is to investigate the ability of the Network Medicine to give deeper insights in the functionality of brain activity. Material and Methods: In the proposed study of Tourette syndrome, we have investigated with the functional magnetic resonance imaging the possibility that the mechanisms associated with the monitoring and internal control of movements were compromised in individuals with Tourette syndrome; we enrolled 20 Tourette Syndrome patients in comparison with a healthy Controls group of 15 subjects matching for age and sex distribution. We proposed, for the fMRI analysis, a novel task based on the execution of switching between complex movements on demand. Results: The elementary activation model found that the effort related to the task in comparing Tourettic vs Controls mainly concerns the areas of the Gyrus of the Cingulum, the precuneus and the thalamic area of the ventral-lateral nucleus. In particular, the BA11 plays an essential role in the Tourette Patients related to the continue tentative to correct the TIC. Considering the status of the pilot study of this work, we remark the power of proposed methods to investigate the complex interaction of the brain networks. Conclusion: Alteration in brain activity for a population of Tourette Syndrome patients is evaluable by the use of complex indexes, results confirm the literature about this pathology and these medical physics methods can be applied to all neurological diseases investigation by opportune task-driven experiments or by resting state fc-MRI experiments

Cardiac computed tomography radiomics: an emerging tool for the non-invasive assessment of coronary atherosclerosis

In the last decades, significant advances have been made in the preventive approaches to cardiovascular disease. Even so, coronary artery disease remains one of the main causes of morbidity and mortality worldwide. Invasive imaging modalities, such as intravascular ultrasound or optical coherence tomography, have played a key role in the comprehension of the pathological processes underlying myocardial infarction and cerebrovascular disease. These imaging techniques have contributed greatly to the identification and phenotyping of the culprit lesion, the so-called vulnerable plaque. Coronary computed tomographic angiography (CCTA) has emerged in more recent years as the non-invasive modality of choice in the study of coronary atherosclerosis, showing in many studies a diagnostic yield comparable to invasive approaches. Moreover, being able to describe extra-luminal characteristics of the affected vessel, CCTA has greatly contributed towards shifting the attention of researchers from the mere quantification of luminal stenosis to the identification of adverse plaque features, which appear to have a stronger prognostic value. However, the identification of some of the hallmarks of vulnerable plaques is qualitative in nature and, therefore, subject to some degree of inter-reader variability. Moreover, CCTA is still unable to identify some fine markers of plaque vulnerability which can be detected by invasive techniques, such as neovascularization and plaque erosion, among others. Nonetheless, radiological images can be viewed as vast 3-D datasets which, via the use of recent technology, allow for the extraction of numerous quantitative features that may be used to accurately phenotype a given lesion. Radiomics is the process of extrapolating innumerable parameters from a given region of interest, with the goal of establishing correlations between quantitative variables and clinical data. These datasets can then be manipulated to create predictive models via the use of automated algorithms in a process called machine learning. As a result of these approaches, radiological images may offer information regarding the characterization of a plaque which can go much beyond the boundaries of what can be qualitatively asserted by the human eye, contributing to expanding the knowledge of the disease and ultimately assist clinical decisions. Thus far, radiomics has found its more consistent area of application in the field of oncology; to present date, the amount of clinical data regarding coronary artery disease is still relatively small, partly due to the technical difficulties associated with the implementation of such techniques to the study of a small and geometrically complex lesion such as the coronary plaque. The present review, after a summary of the imaging modalities most commonly used nowadays in the study of coronary plaques, will provide a perspective on the application of radiomic analysis to coronary artery disease

Mentalizing subtypes in eating disorders: A latent profile analysis

Background: Mentalizing, the mental capacity to understand oneself and others in terms of mental states, has been found to be reduced in several mental disorders. Some studies have suggested that eating disorders (EDs) may also be associated with impairments in mentalizing. The aim of this work is to investigate the possible presence of mentalizing subtypes in a sample of patients with EDs. Method: A sample of patients with eating disorders (N = 157) completed a battery of measures assessing mentalization and related variables, including the Reflective Functioning Questionnaire (RFQ), the Difficulties in Emotion Regulation Strategies (DERS), the Interpersonal Reactivity Index (IRI). Clinicians rated patients in relation to imbalances in different dimensions of mentalization to prementalizing modes and attachment style by using the Mentalization Imbalances Scale, the Modes of Mentalization Scale (MMS), and the Adult Attachment Questionnaire. A latent profile analysis was conducted to test the possible presence of different subgroups. MANOVA was used to test the possible differences between the four mentalizing profiles in relation to emotion dysregulation (DERS), empathy (IRI), and adequate and impairments in mentalizing (MMS and RFQ). Results: The latent profile analysis suggested the presence of four different profiles in relation to impairments in the dimensions of mentalization: (1) affective/self/automatic imbalances, (2) external imbalance, (3) cognitive/self/automatic imbalances, and (4) cognitive/other/automatic imbalances. Patients belonging to profile 1 are characterized by the prevalence of affective mentalization that overwhelms the capacity to reflect on mental states with an imbalance on the self-dimension; profile 2 patients are excessively focused on the external cues of mentalization; profile 3 patients are characterized by an over-involvement on the cognitive and self-facets of mentalization, with an impairment in adopting the other mind perspective; and profile 4 patients have similar impairments compared to profile 3 patients but with an excessive focus on others and deficits in self-reflection. These profiles were heterogeneous in terms of EDs represented in each group and presented significant differences on various variables such as attachment style, emotion dysregulation, empathy, interpersonal reactivity, and reflective function. This study represents, so far, the first work that confirms the presence of different mentalizing patterns in ED patients. Conclusions: ED patients can be classified in relation to impairments in different dimensions of mentalization above and beyond ED diagnosis

Trichoderma Enzymes for Degradation of Aflatoxin B1 and Ochratoxin A.

The contamination of agricultural products with mycotoxins causes risks to animal and human health and severe economic losses. Mycotoxicoses can be reduced by preventing fungal infection using chemical and biological approaches. The chemical strategies can release toxic molecules; therefore, strategies for biological control are being evaluated, such as using nontoxic fungi and their metabolites. This work evaluated the effect of exoenzymes produced by the beneficial fungus Trichoderma afroharzianum strain T22 in degrading Aflatoxin B1 (AFB1) and Ochratoxin A (OTA). The ability of Trichoderma to produce hydrolases was stimulated by using different inducing substrates. The highest AFB1 and OTA degradation activity was obtained using a medium containing lyophilized mushrooms and crude fiber. The T. afroharzianum T22's ability to reduce mycotoxins may be attributed to peroxidase enzymes. This study showed that T. afroharzianum strain T22 or its peroxidase supplementation could represent a sustainable strategy for the degradation of AFB1 and OTA in feed and food products

Inhibition of IκBα phosphorylation potentiates regulated cell death induced by azidothymidine in HTLV-1 infected cells

Adult T cell leukemia/lymphoma (ATL) can be susceptible, at least transiently, to treatments with azidothymidine (AZT) plus IFNα and/or arsenic trioxide. However, the real role of AZT in this effect is still unclear. In fact, while reverse transcriptase (RT) inhibition could explain reduction of clonal expansion and of renewal of HTLV-1 infected cells during ATL progression, this effect alone seems insufficient to justify the evident and prompt decrease of the pro-viral load in treated patients. We have previously demonstrated that AZT is endowed with an intrinsic pro-apoptotic potential towards both peripheral blood mononuclear cells from healthy donors or some tumor cell lines, but this cytotoxic potential cannot be fully achieved unless IκBα phosphorylation is inhibited. Since the constitutive activation of NF-kappa B (NF-κB) appears a common biological basis of HTLV-1-infected cells, a pharmacological inhibition of IκBα phosphorylation seems a potential strategy for treating and preventing HTLV-1 related pathologies. In this study, we have demonstrated that a combination treatment with the IκBα phosphorylation inhibitor Bay 11-7085 and AZT induced increased levels of regulated cell death (RCD) by apoptosis compared to the single treatments in HTLV-1 infected cells of different origin. Importantly, levels of RCD were considerably higher in infected cells in comparison with the uninfected ones. Inhibition of NF-κB activation following the combined treatment was confirmed by analysis of both gel-shift and functional activity of the NF-κB complex proteins, p65/p52. Moreover, a transcriptional analysis revealed that the addition of Bay 11-7085 to AZT treatment in HTLV-1-infected cells modified their transcriptional profile, by inducing the upregulation of some pro-apoptotic genes together with the downregulation of some anti-apoptotic genes. Our data suggest that addition of adequate concentrations of IκBα phosphorylation inhibitor to therapeutic regimens including AZT could be a promising strategy in ATL

Multicentre narrative research on major depression to integrate the experiences of patients, their caregivers and healthcare providers in Italy

OBJECTIVE: This research aimed to investigate the experience of major depression by integrating the perspectives of patients, caregivers and healthcare providers through narrative-based medicine (NBM) to provide new insights to improve care relationships. DESIGN AND SETTING: The research was conducted in 2019 and involved five Italian psychiatric centres and targeted adult patients, their caregivers and healthcare providers to address data source triangulation. A sociodemographic survey and a narrative plot, based on Natural Semantic Metalanguage were collected. Narratives were analysed through NBM classifications, NVivo software and interpretative coding. PARTICIPANTS: Thirty-six patients with a diagnosis of major depression, 27 caregivers and 33 healthcare providers participated in the research. RESULTS: Among the 96 collected narratives, 'lonely' was the word patients used most frequently, while 'sad' and 'lifeless' were used most respectively by caregivers and healthcare providers. A positive care relationship was crucial for 84% of patients in relation to their care pathway, and nature (36%) and the arts (28%) were the most frequent resources. Caregivers expressed feelings of powerlessness and inadequacy, and 21% of them reported a declining social life while providing care to a loved one with depression. Thirty-one percent of mental health professionals experienced difficulties in their first encounter with patients; however, their emotions progressively moved towards trust and satisfaction. Furthermore, 89% of patients and healthcare providers and 58% of caregivers evaluated writing the narrative to be a positive experience. CONCLUSION: Findings suggested the possible role for language in understanding major depression, thereby improving care relationships between patients and physicians. Care pathways might also be more attentive to caregivers, to reduce their risk of burnout. Finally, narrative medicine could be integrated with the care pathway as an additional space of expression, dialogue, reflection and development of empathy