Evidenced-based medicine

Aim: BCRP plays a major role in the efflux of cytotoxic molecules, limiting their antiproliferative activity. We aimed to design and synthesize new BCRP inhibitors to render cancerous tumors more sensitive toward anticancer agents. Materials & methods: Based on our previous work, we conceived potential BCRP inhibitors derived from 1,3,4-oxadiazoles bearing two substituted phenyl rings. Results: Evaluating 19 derivatives, we found that 2,5-diaryl-1,3,4-oxadiazoles possessing methoxy groups were the most active...

The feeding strategies of the first domesticated herds had to manage the risks arising from the novelty of livestock practices in territories often distant from the animals' primary habitats. The Iberian Peninsula is characterised by a great diversity of environments, which undoubtedly influenced these dynamics. At the beginning of the Neolithic period these led the possibility to combine diverse livestock farming practices based on different animal feeding habits. This variability is also consistent with the rythms of adoption of domesticated animals, being later on the northern area...

A novel small molecule based on benzothiazole-piperazine has been identified as an effective multi-target-directed ligand (MTDL) against Alzheimer's disease (AD). Employing a medicinal chemistry approach, combined with molecular docking, MD simulation, and binding free energy estimation, compound 1 emerged as a potent MTDL against AD. Notably, compound 1 demonstrated efficient binding to both AChE and Aβ1-42, involving crucial molecular interactions within their active sites. It displayed a binding free energy (ΔGbind ) -18...

We have previously shown that after few seconds of adaptation by finger-tapping, the perceived numerosity of spatial arrays and temporal sequences of visual objects displayed near the tapping region is increased or decreased, implying the existence of a sensorimotor numerosity system (Anobile et al., 2016). To date, this mechanism has been evidenced only by adaptation. Here, we extend our finding by leveraging on a well-established covariance technique, used to unveil and characterize 'channels' for basic visual features such as colour, motion, contrast, and spatial frequency...

BACKGROUND: Selective androgen receptor modulators (SARMs) are small synthetic drug molecules that are still not approved as medicine in Europe or the United States but are sold on illegal websites to improve sport performance, particularly bodybuilding. AIM: To address the quality issues of illegal SARM products and their increasing diffusion in Italy with their potential health risks for consumers. METHODS: Web-based tools were used to investigate retail websites, trending searches, and information exchange via social media...

BACKGROUND: Blood pressure is a vital sign for organ perfusion that anesthesiologists measure and modulate during surgery. However, current decision-making processes rely heavily on clinicians' experience, which can lead to variability in treatment across surgeries. With the advent of machine learning, we can now create models to predict the outcomes of interventions and guide perioperative decision-making. The first step in this process involves translating the clinical decision-making process into a framework understood by an algorithm...

What cannot be measured will not be managed. The Global Burden of Animal Diseases (GBADs) will generate information on animal disease burdens by species, production system, type and gender of farmer and consumer, geographical region, and time period. To understand the demand for burden of animal disease (BAD) data and how end-users might benefit from this, we reviewed the literature on animal diseases prioritisation processes (ADPP) and conducted a survey of BAD information users. The survey covered their current use of data and prioritizations as well as their needs for different, more, and better information...

Unhealthy behaviors may contribute to the development and the progression of chronic diseases with negative consequences on patients' quality of life. The present study aimed to investigate the relationship between unhealthy behaviors (physical inactivity, tobacco consumption, and alcohol consumption) and health-related quality of life, measured with the SF-36 questionnaire, in women with endometriosis. To achieve this, data from a previous cross-sectional web survey among Italian adult women were analyzed...

The extraordinary success that chimeric antigen receptor (CAR) T cell therapies have shown over the years on fighting hematological malignancies is evidenced by the six FDA-approved products present on the market. CAR T treatments have forever changed the way we understand cellular immunotherapies, as current research in the topic is expanding even outside the field of cancer with very promising results. Until now, virus-based strategies have been used for CAR T cell manufacturing. However, this methodology presents relevant limitations that need to be addressed prior to wide spreading this technology to other pathologies and in order to optimize current cancer treatments...

BACKGROUND: Yinhua Miyanling tablets (YMT), comprising 10 Chinese medicinal compounds, is a proprietary Chinese medicine used in the clinical treatment of urinary tract infections. Medicinal compounds, extracts, or certain monomeric components in YMT all show good effect on ulcerative colitis (UC). However, no evidence supporting YMT as a whole prescription for UC treatment is available. PURPOSE: To evaluate the anti-UC activity of YMT and elucidate the underlying mechanisms...

The 2017 World Health Organization Fact Sheet highlights that coronary artery disease is the leading cause of death globally, responsible for approximately 30% of all deaths. In this context, machine learning (ML) technology is crucial in identifying coronary artery disease, thereby saving lives. ML algorithms can potentially analyze complex patterns and correlations within medical data, enabling early detection and accurate diagnosis of CAD. By leveraging ML technology, healthcare professionals can make informed decisions and implement timely interventions, ultimately leading to improved outcomes and potentially reducing the mortality rate associated with coronary artery disease...

Among the available diagnostic techniques, antibody detection in bulk tank milk (BTM) represents a useful tool to estimate and monitor Neospora caninum herd prevalence. To evaluate the prevalence of N. caninum and the effect of parasite infection on herd performances, BTM samples collected from 586 dairy herds located in one of the largest dairy production areas in Italy (Lombardy) were analyzed by an indirect ELISA to detect anti-N. caninum specific antibodies. Generalized linear models (GLMs) were developed...

Pandemic-related distancing regulations gave medical educators at our college an opportunity to reimagine and expand our evidenced-based medicine curriculum to an asynchronous, virtual format. We share the experience of course directors, faculty, and students with our new surgical journal club format. Our goal was to support learners' critical appraisal skills of the surgical literature through active learning modalities such as visual abstract generation and audio-synopsis creation. We included surgeons whose practice locations and schedules may preclude participation...

This article introduces a cutting-edge H∞ model-based control method for uncertain Multi Input Multi Output (MIMO) systems, specifically focusing on UAVs, through a flexible mixed-optimization framework using the Method of Inequality (MOI). The proposed approach adaptively addresses crucial challenges such as unmodeled dynamics, noise interference, and parameter variations. Central to the design is a two-step controller development process. The first step involves Nonlinear Dynamic Inversion (NDI) and system decoupling for simplification, while the second step integrates H∞ control with MOI for optimal response tuning...

Partial reprogramming by cyclic short-term expression of Yamanaka factors holds promise for shifting cells to younger states and consequently delaying the onset of many diseases of aging. However, the delivery of transgenes and potential risk of teratoma formation present challenges for in vivo applications. Recent advances include the use of cocktails of compounds to reprogram somatic cells, but the characteristics and mechanisms of partial cellular reprogramming by chemicals remain unclear. Here, we report a multi-omics characterization of partial chemical reprogramming in fibroblasts from young and aged mice...

BACKGROUND: There is little evidence on how to support ultra-poor people with disabilities to adopt sustainable livelihoods. The Disability-Inclusive Graduation (DIG) programme targets ultra-poor people with disabilities and/or women living in rural Uganda. The programme is an adaptation of an ultra-poor graduation model that has been shown to be effective in many contexts but not evaluated for people with disabilities. METHODS: The DIG programme works with project participants over a period of 18 months...

PURPOSE: Current guidelines for the management of metastatic non-small cell lung cancer (NSCLC) without driver mutations recommend checkpoint immunotherapy with PD-1/PD-L1 inhibitors, either alone or in combination with chemotherapy. This approach fails to account for individual patient variability and host immune factors and often results in less-than-ideal outcomes. To address the limitations of the current guidelines, we developed and subsequently blindly validated a machine learning algorithm using pretreatment plasma proteomic profiles for personalized treatment decisions...

The inhibition of the α-glucosidase enzyme is crucial for targeting type 2 diabetes mellitus (DM). This study introduces a series of synthetic analogs based on thiomethylacetamide-quinoline derivatives linked to diphenyl-imidazole as highly potential α-glucosidase inhibitors. Twenty derivatives were synthesized and screened in vitro against α-glucosidase, revealing IC50 values ranging from 0.18 ± 0.00 to 2.10 ± 0.07 μM, in comparison to the positive control, acarbose...

The misuse and overdose of antimicrobial medicines are fostering the emergence of novel drug-resistant pathogens, providing negative repercussions not only on the global healthcare system due to the rise of long-term or chronic patients and inefficient therapies but also on the world trade, productivity, and, in short, to the global economic growth. In view of these scenarios, novel action plans to constrain this antibacterial resistance are needed. Thus, given the proven antiproliferative tumoral and microbial features of thiosemicarbazone (TSCN) ligands, we have here synthesized a novel effective antibacterial copper-thiosemicarbazone complex, demonstrating both its solubility profile and complex stability under physiological conditions, along with their safety and antibacterial activity in contact with human cellular nature and two most predominant bacterial strains, respectively...

A novel family of precision-engineered gene vectors with well-defined structures built on trehalose and trehalose-based macrocycles (cyclotrehalans) comprising linear or cyclic polyamine heads have been synthesized through procedures that exploit click chemistry reactions. The strategy was conceived to enable systematic structural variations and, at the same time, ensuring that enantiomerically pure vectors are obtained. Notably, changes in the molecular architecture translated into topological differences at the nanoscale upon co-assembly with plasmid DNA, especially regarding the presence of regions with short- or long-range internal order as observed by TEM...