20 research outputs found
Drug repositioning: current approaches and their implications in the precision medicine era
Introduction: Drug repositioning implies finding new medical uses for existing drugs. It represents a cost-efficient approach, since the new indications are built on the basis of available information on pharmacokinetics, safety and manufacturing. Whereas most of the pioneering drug repurposing stories arose from serendipitous observations and clever exploitation of side effects, the drug discovery community has lately addressed repurposing initiatives in a more systematic manner. Today, in the middle of the omics era, we have the tools to explore drug repurposing opportunities in a tailored, personalized manner. Areas covered: After a brief discussion on modern approaches to drug repurposing, the author connects the philosophies of drug repurposing and personalized medicine through the well-known and extended practice of off-label prescription. The author also discusses which, among current systematic repurposing approaches, are more appropriate to be integrated with the field of precision medicine. Expert commentary: Personalized drug repurposing is not a new concept at all: for years, it has been known as off-label prescription, a practice widely accepted especially in some branches of medicine. Whereas in the past such approach was in many cases supported by empiric knowledge, today omics technologies allow us to face novel personalized drug repurposing options in a systematic manner.Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
An Italian validation of the Psychological Maltreatment Review (PMR)
PURPOSE: The aim of the current study was to evaluate the construct validity and the internal consistence of the Italian version of the Psychological Maltreatment Review (PMR), and to assess the concurrent validity to provide adequate and reliable instruments to measure retrospectively child psychological maltreatment in the Italian population. METHODS: The participants to our study were 209 patients and 217 nonclinical subjects. The first group consisted in 209 adult patients, 106 males and 103 females (mean age of 41.43 years; SD=12.34) consecutively admitted at the psychiatric unit of the L'Aquila San Salvatore Hospital. The second group consisted in 217 non-clinical subjects, 96 males and 121 females (mean age of 36.38; SD=10.38) that completed an online survey, including the self-report version of the PMR and the Risky Families Questionnaire (RFQ). All subjects were invited to answer to Sociodemographic Information Form and to take a self-report battery composed by two instruments: the Psychological Maltreatment Review (PMR) and the RFQ. RESULTS: Internal consistency reliability analyses were performed separately for the two samples, all the scales had very good internal consistency in both samples, with Cronbach's alpha coefficients equal or greater than .88. An EFA was performed, using exploratory principal axis factoring, on the data of individuals from the non-clinical sample, separately for paternal and maternal scales, followed by varimax rotation and scree testing. The CFA was performed on the data of the patients' sample, separately for paternal and maternal scales, supported a three factor model yielding the best fit indexes, both for paternal scales, χ 2 =725, p<.001; df=402, CFI=0.92; TLI=0.91, SRMR=0.053, RMSEA=0.063, 90% CI [0.056, 0.07]; and maternal scales, χ 2 =758, p<.001; df=374, CFI=0.89; TLI=0.88, SRMR=0.064, RMSEA=0.07, 90% CI [0.06, 0.07]. The CFA performed on the patient' sample supported a three factor model yielding the best fit indexes. The convergence of the EFA and the CFA in different samples supported the structural validity of the PMR and replicated its factorial structure, for both maternal and paternal ratings. CONCLUSIONS: This study provides evidence on the appropriateness of the Italian version of the PMR to retrospectively measure childhood psychological maltreatment. The three PMR scales (psychological abuse, psychological neglect and psychological support) demonstrated good internal consistency with average alpha coefficients, equal or greater than .88. The findings provide evidence of the construct validity, according to the literature, suggesting that psychological abuse, psychological neglect and parental support are dimensionally separated constructs, as defined in the literature
Computational approaches for innovative antiepileptic drug discovery
Introduction: Despite the approval of a large number of antiepileptic agents over the past 25 years, there has been no significant improvement in efficacy of treatments, with one third of patients suffering from intractable epilepsy. This scenario has prompted the search for innovative drug discovery solutions. While network pharmacology and explanations of the drug resistance phenomena have been proposed to drive the search for more efficacious therapeutic solutions, such alternative approaches have not fully taken hold within the antiepileptic drug discovery community so far. Areas covered: Herein, the author discusses the impact that network pharmacology and the current hypotheses of refractory epilepsy and drug repurposing could have if integrated with anti-epileptic computer-aided discovery. Expert opinion: With many complex diseases, the advancement in the understanding of disorder pathophysiology in addition to the contribution of systems biology have rapidly translated into the discovery of novel drug candidates. However, antiepileptic drug developers have fallen a little behind in this regard, with fewer examples of computer-aided antiepileptic drug design and network-based approximations appearing in scientific literature. New generation single-target agents have so far shown limited success in terms of enhanced efficacy; in contrast, multi-target agents could possibly demonstrate improved safety and efficacy.Fil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Cátedra de Química Medicinal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
Music Hospital: An acceptability study of music therapy activities in a psychiatric ward through listening and analysis of author tunes
: A study was conducted on the acceptability of a music therapy intervention in a group context, in a psychiatric ward where people with acute psychopathological conditions are hospitalized. The objectives of the intervention are both therapeutic (stress reduction) and informative-descriptive, on topics ranging from stress management, to the first signs of crisis and drugs. For this purpose, musical stimuli provided by the presentation, listening and analysis of author's pieces were used, through the diffusion of pleasant sounds at moderate rhythm and volume among patients and operators. Acceptability was assessed through a satisfaction questionnaire. The responses to the questionnaire were very positive, confirming the narrative observations of the operators who found favorable ways of interacting with the patients with whom they shared the activity in all its contents. Participation in the music therapy intervention in a group context led users to an improvement in their stress management skills and to a more positive adaptation to the condition of hospitalization
Mental health outcomes of the CoViD-19 pandemic
The coronavirus disease 2019 (CoViD-19) caused by the novel Coronavirus strain SARS-CoV-2 is currently a pandemic. On January 30, 2020, the World Health Organization declared that the CoViD-19 outbreak is a public health emergency of international concern. The virus has already had a direct impact on the physical health of million people, and besides, it is supposed to pose a mental health threat of great magnitude globally. This review aims at synthesizing mounting evidence concerning the immediate psychological responses during the initial stage of the CoViD-19 pandemic among the general population, the health-care workers, and clinical populations. Experts point out the need to pay specific attention to other groups at risk of further distress that may need tailored interventions. Providing psychological first aid is an essential care component for populations that have been victims of emergencies and disasters, before, during and after the event. With the aim of dealing better with the urgent psychological problems of people involved in the CoViD-19 pandemic, a new psychological crisis intervention model is needed. Given the recommendation to minimize face-to-face interaction, online mental health services have been widely adopted in China and are urged in other countries
Source monitoring task in a sample of in-patients with verbal auditory hallucinations compared to control sample
Patients with psychosis, especially those with specific positive symptoms such as auditory verbal hallucinations, show a source monitoring deficit, the cognitive process involved in the recognition of the information source. This defect can lead to the erroneous conclusion that self-generated thoughts are not "proper" but derive from an external source. We evaluated 37 patients diagnosed with psychotic disorder and 40 healthy controls using a modified version of the Reality Monitoring Task developed by Larøi et al. in 2004. The patients were also evaluated with PANSS, VGF, PSP. We have found that the performance of the Source Monitoring Task differs between patients with hallucinations and controls. According to the literature we can therefore state that patients with hallucinations are characterized by a difficulty in identifying the source of the information they perceive. Our study also adds a new finding to the literature: the source monitoring dysfunction is not due to the presence of current hallucinatory symptomatology but could be considered a stable trait in psychotic patients
Molecular characterization and drug susceptibility of non-O1/O139 V. cholerae strains of seafood, environmental and clinical origin, Italy
Toxigenic and antimicrobial susceptibility patterns and genetic relatedness of 42 non-O1/O139 V. cholerae
strains, the majority of them isolated from seafood and marine water of the Adriatic sea, Italy, and 9
clinical strains, two of which with seawater of the Adriatic as the source of infection, were studied. All
strains had hlyA El Tor gene but lacked ctxA gene. Four and two isolates, respectively, also had stn/sto and
tcpA Class genes. More than 90% of strains showed susceptibility to cefotaxime, ciprofloxacin, cloramphenicol,
tetracycline, trimethoprim þ sulfamethoxazole and intermediate or full resistance to
tetracycline and erythromycin. Six strains of seafood and clinical source were multi-drug resistant. PFGE
analysis allowed to type all the strains with 50 banding patterns. Twenty-one strains, 11 and 8 from
seafood and seawater, respectively, and 2 of clinical origin, were grouped into 9 different clusters. We
report the presence of toxigenic and multidrug resistant non-O1/O139 V. cholerae strains in Adriatic,
some of which genetically related, and support that they represent a potential reservoir of toxin and
antibiotic resistance genes
The Microbial Diversity of Non-Korean Kimchi as Revealed by Viable Counting and Metataxonomic Sequencing
Kimchi is recognized worldwide as the flagship food of Korea. To date, most of the currently
available microbiological studies on kimchi deal with Korean manufactures. Moreover, there is a
lack of knowledge on the occurrence of eumycetes in kimchi. Given these premises, the present
study was aimed at investigating the bacterial and fungal dynamics occurring during the natural
fermentation of an artisan non-Korean kimchi manufacture. Lactic acid bacteria were dominant, while
Enterobacteriaceae, Pseudomonadaceae, and yeasts progressively decreased during fermentation.
Erwinia spp., Pseudomonas veronii, Pseudomonas viridiflava, Rahnella aquatilis, and Sphingomonas spp.
were detected during the first 15 days of fermentation, whereas the last fermentation phase was
dominated by Leuconostoc kimchi, together withWeissella soli. For the mycobiota at the beginning of the
fermentation process, Rhizoplaca and Pichia orientalis were the dominant Operational Taxonomic Units
(OTUs) in batch 1, whereas in batch 2 Protomyces inundatus prevailed. In the last stage of fermentation,
Saccharomyces cerevisiae, Candida sake, Penicillium, and Malassezia were the most abundant taxa in
both analyzed batches. The knowledge gained in the present study represents a step forward in
the description of the microbial dynamics of kimchi produced outside the region of origin using
local ingredients. It will also serve as a starting point for further isolation of kimchi-adapted
microorganisms to be assayed as potential starters for the manufacturing of novel vegetable preserves
with high quality and functional traits
Glitching. Processi dinamici e azioni evolutive per la rigenerazione urbana
L'area di Santa Giulia a Milano è caratterizzata da molteplici relazioni a livello territoriale e urbano. Questo complesso quadro relazionale richiede una riflessione sulle dinamiche di evoluzione ambientale, economica e sociale che potrebbero verificarsi a breve e lungo termine, con implicazioni significative sui futuri processi di rigenerazione urbana. L'imprevedibilità dei cambiamenti negli utenti, nelle funzioni, negli scenari climatici, nelle attività socioeconomiche e nel mercato immobiliare non richiede un progetto statico e immutabile, ma un sistema di interventi in grado di adattarsi ed evolvere rispetto ad alcune relazioni emergenti, aperte e in costante cambiamento. La proposta di progetto per l'insediamento di via Medici del Vascello mira a un modello che rompe gli schemi di pianificazione utilizzati finora, generando un "errore nel sistema urbano": un "glitch". L'idea del glitch è di creare un disturbo per alterare l'equilibrio, interrompere una logica di insediamento dedicata alla completezza funzionale e formale, iper-efficiente ma incapace di relazionarsi con l'ambiente circostante, finalizzato alla chiusura, destinato all'isolamento e all'autoesclusione. La proposta di progetto del team Coast2Coast mira a invertire l'approccio alla base della pratica di pianificazione degli ultimi decenni, proponendo non un distretto autosufficiente ma concependo la possibilità di riattivare e ricollegare diverse parti della città attraverso processi dinamici e azioni evolutive di rigenerazione urbana.Santa Giulia area in Milan is characterized by multiple territorial and urban level relationships. This complex relational framework requires a reflection on the dynamics of environmental, economic and social evolution that could occur from the short to the long term, with significant implications on forthcoming urban regeneration processes. The unpredictability of changes in users, functions, climate scenarios, socio-economic assets and real estate market requires not a static and immutable project, but a system of interventions capable of adaptation and evolution with respect to some emerging, open and constantly changing relationships. The project proposal for via Medici del Vascello settlement aims at a model that breaks the planning schemes perpetuated so far, generating a “mistake in the urban system”: a “glitch”. The idea of the glitch is to create a disturbance to alter the balance, to disrupt a settlement logic devoted to functional and formal completeness, hyper-efficient but unable to relate with the surroundings, aimed at closure, fated to isolation and self-exclusion. Coast2Coast team’s project proposal aims to invert the approach behind the planning practice of the last decades, no longer proposing a self-sufficient district but rather conceiving the chance to reactivate and reconnect different parts of the city through dynamic processes and evolutionary actions of urban regeneration
Antiseizure medication discovery: Recent and future paradigm shifts
Despite the ever‐increasing number of available options for the treatment of epilepsies and the remarkable advances on the understanding of their pathophysiology, the proportion of refractory patients has remained approximately unmodified during the last 100 years. How efficient are we translating positive outcomes from basic research to clinical trials and/or the clinical scenario? It is possible that fresh thinking and exploration of new paradigms are required to arrive at truly novel therapeutic solutions, as seemingly proven by recently approved first‐in‐class antiseizure medications and drug candidates undergoing late clinical trials. Here, the author discusses some approximations in line with the network pharmacology philosophy, which may result in highly innovative (and, hopefully, safer and/or more efficacious) medications for the control of seizures, as embodied with some recent examples in the field, namely tailored multi‐target agents and low‐affinity ligands
