Assessment of Mental Workload: a Comparison of Machine Learning Methods and Subjective Assessment Techniques

Mental workload (MWL) measurement is a complex multidisciplinary research field. In the last 50 years of research endeavour, MWL measurement has mainly produced theory-driven models. Some of the reasons for justifying this trend includes the omnipresent uncertainty about how to define the construct of MWL and the limited use of datadriven research methodologies. This work presents novel research focused on the investigation of the capability of a selection of supervised Machine Learning (ML) classification techniques to produce data-driven computational models of MWL for the prediction of objective performance. These are then compared to two state-of-the-art subjective techniques for the assessment of MWL, namely the NASA Task Load Index and the Workload Profile, through an analysis of their concurrent and convergent validity. Findings show that the data-driven models generally tend to outperform the two baseline selected techniques

Synthesis of sericin-based conjugates by click chemistry: enhancement of sunitinib bioavailability and cell membrane permeation

Sericin is a natural protein that has been used in biomedical and pharmaceutical fields as raw material for polypeptide-based drug delivery systems (DDSs). In this paper, it has been employed as pharmaceutical biopolymer for the production of sunitinib–polypeptide conjugate. The synthesis has been carried out by simple click reaction in water, using the redox couple l-ascorbic acid/hydrogen peroxide as a free radical grafting initiator. The bioconjugate molecular weight (50 kDa < Mw < 75 kDa) was obtained by SDS-PAGE, while the spectroscopic characteristics have been studied in order to reveal the presence of grafted sunitinib. In both FT-IR and UV/Vis spectra, signals corresponding to sunitinib functional groups have been identified. Since sunitinib is an anticancer drug characterized by low bioavailability and low permeability, the bioconjugation aimed at their enhancement. In vitro studies demonstrated that bioavailability has been increased to almost 74%, compared with commercial formulation. Also cell membrane permeability has been augmented in in vitro tests, in which membrane models have been used to determine the lipid membrane/physiological fluid partition coefficient (Kp). The log(Kp) value of the bioconjugate was increased to over 4. This effect resulted in a three-fold decrease of IC50 value against MCF-7 cells

A Look at the Importance of Chirality in Drug Activity: Some Significative Examples

[EN] Chirality plays an important role in the development of many pharmaceuticals, being a general property of 'handedness'; nevertheless, a large number of pharmaceuticals are still marketed and administered as racemates. Chirality is all around and even within us; indeed, receptors and enzymes are chiral entities and interact in a specific manner with chiral drugs. Consequently, controlling enantiomeric purity and isolating the enantiomers from chiral drugs remains a crucial subject for analytical, clinical, and regulatory purposes, thus, improving the drug safety profile. The classical examples of spontaneous enantiomerization and severe toxicity related to chirality are represented by ibuprofen and thalidomide, respectively, but numerous other cases have been reported in the literature. This review intends to offer a brief overview on the most common chiral drugs used in therapy for the treatment of various diseases.Ceramella, J.; Iacopetta, D.; Franchini, A.; De Luca, M.; Saturnino, C.; Andreu, I.; Sinicropi, MS.... (2022). A Look at the Importance of Chirality in Drug Activity: Some Significative Examples. Applied Sciences. 12(21):1-22. https://doi.org/10.3390/app122110909122122

Stoke Prevention in Diabetes

Diabetes and ischemic stroke are common disorders that often arise together. Diabetics are at 1.5 to three times the risk of stroke compared with the general population and the associated mortality and morbidity is greater than in those without this underlying condition. Importantly, the relation between disturbed glucose metabolism and cerebrovascular disease is not restricted to acute ischemic stroke. Diabetes is also associated with more insidious ischaemic damage to the brain, mainly manifesting as small-vessel disease and increased risk of cognitive decline and dementia. This paper shows the epidemiologic relationships of stroke in type 2 diabetes and suggest that rigorous assessment and treatment of associated risk factors can substantially reduce the risk of stroke in patients with diabetes

A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth

Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer

Quercetin derivatives as novel antihypertensive agents: Synthesis and physiological characterization

The antihypertensive flavonol quercetin (Q1) is endowedwith a cardioprotective effect againstmyocardial ischemic damage. Q1 inhibits angiotensin converting enzymeactivity, improves vascular relaxation, and decreases oxidative stress and gene expression. However, the clinical application of this flavonol is limited by its poor bioavailability and low stability in aqueous medium. In the aimto overcome these drawbacks and preserve the cardioprotective effects of quercetin, the present study reports on the preparation of five different Q1 analogs, in which all OH groups were replaced by hydrophobic functional moieties. Q1 derivatives have been synthesized by optimizing previously reported procedures and analyzed by spectroscopic analysis. The cardiovascular properties of the obtained compounds were also investigated in order to evaluate whether chemical modification affects their biological efficacy. The interaction with β-adrenergic receptors was evaluated by molecular docking and the cardiovascular efficacy was investigated on the ex vivo Langendorff perfused rat heart. Furthermore, the bioavailability and the antihypertensive properties of the most active derivative were evaluated by in vitro studies and in vivo administration (1month) on spontaneously hypertensive rats (SHRs), respectively. Among all studied Q1 derivatives, only the ethyl derivative reduced left ventricular pressure (at 10−8M÷10−6Mdoses) and improved relaxation and coronary dilation. NOSs inhibition by L-NAME abolished inotropism, lusitropism and coronary effects. Chronic administration of high doses of this compound on SHR reduced systolic and diastolic pressure. Differently, the acetyl derivative induced negative inotropism and lusitropism (at 10−10M and 10−8 ÷ 10−6 M doses), without affecting coronary pressure. Accordingly, docking studies suggested that these compounds bind both β1/β2-adrenergic receptors. Taking into consideration all the obtained results, the replacement of OHwith ethyl groups seems to improve Q1 bioavailability and stability; therefore, the ethyl derivative could represent a good candidate for clinical use in hypertension

The incidence of hip, forearm, humeral, ankle, and vertebral fragility fractures in Italy: results from a 3-year multicenter study

INTRODUCTION: We aimed to assess the incidence and hospitalization rate of hip and "minor" fragility fractures in the Italian population. METHODS: We carried out a 3-year survey at 10 major Italian emergency departments to evaluate the hospitalization rate of hip, forearm, humeral, ankle, and vertebral fragility fractures in people 45 years or older between 2004 and 2006, both men and women. These data were compared with those recorded in the national hospitalizations database (SDO) to assess the overall incidence of fragility fractures occurring at hip and other sites, including also those events not resulting in hospital admissions. RESULTS: We observed 29,017 fractures across 3 years, with hospitalization rates of 93.0% for hip fractures, 36.3% for humeral fractures, 31.3% for ankle fractures, 22.6% for forearm/wrist fractures, and 27.6% for clinical vertebral fractures. According to the analyses performed with the Italian hospitalization database in year 2006, we estimated an annual incidence of 87,000 hip, 48,000 humeral, 36,000 ankle, 85,000 wrist, and 155,000 vertebral fragility fractures in people aged 45 years or older (thus resulting in almost 410,000 new fractures per year). Clinical vertebral fractures were recorded in 47,000 events per year. CONCLUSIONS: The burden of fragility fractures in the Italian population is very high and calls for effective preventive strategies

Do we need to categorize it? Reflections on constituencies and quotas as tools for negotiating difference in the global food sovereignty convergence space

Convergence–as an objective and as a process–designates the coming together of different social actors across strategic, political, ideological, sectoral and geographic divides. In this paper, we analyze the global food sovereignty movement (GFSM) as a convergence space, with a focus on constituencies and quotas as tools to maintain diversity while facilitating convergence. We show how the use of constituencies and quotas has supported two objectives of the GFSM: alliances building and effective direct representation in global policy-making spaces. We conclude by pointing to some convergence challenges the GFSM faces as it expands beyond its agrarian origins.</p

O professor e o aluno do ensino fundamental em sala de aula: indisciplina ou indícios de TDAH? / The teacher and student in classroom education: indiscipline or ADHD?

Este artigo é desenvolvido no contexto da psicopegadogia, e tem como objetivo “propor uma sistemática  para  os  professores  de  Ensino  Fundamental  a  distinguirem  comportamentos  de indisciplina  de  índicos  de  TDAH  de seus  alunos  em  sala  de  aula  (crianças  de  7  a  12  anos incompletos)”. O estudo é desenvolvido como uma pesquisa explicativa/analítica, bibliográfica e qualitativa, valendo-se da coleta de dados em fontes ecundárias (artigos, livros, trabalhos científicos).  Tem  como  base  principal  as  obras  de  Garcia  (1999),  Freller  (2001), Estrela  (1992),  Vasconcellos  (1994),  Benczik  e  Rohde  (1999),  Topczewski  (1999)  e  Diniz Neto e Sena (2007), dentre outras, as quais levam a argumentações e conclusões pelo método dedutivo.  Justifica-se  sua  elaboração  por  responder  uma  questão  polêmica  na  atualidade: “Como o professor de Ensino Fundamental pode distinguir os comportamentos de indisciplina ou  indícios  de  TDAH  em  sala  de  aula?  Tem como resposta cinco passos de ações, em um crescente de conhecimentos. Os quatros primeiros dirigem-se a conhecer personalizadamente o aluno a julgar, se auto conhecer didática-profissionalmente, saber o que é a indisciplina do aluno em sala de aula,  o que é o TDAH, e quais os comportamentos característicos do estágio cognitivo das operações  concretas. E o quinto faz a distinção entre os comportamentos das crianças. Conclui-se que: (a) Aluno de comportamento normal (tem comportamento esperado junto à turma; quebra regras e preceitos apenas quando motivado pelo professor; e não tem indícios de   TDAH). (b) Aluno de comportamento indisciplinado (quebra regras e preceitos do  professor  ou  da  escola  sem  motivação  do  professor;  e  não  tem  indícios  de  TDAH).  (c) Aluno  com  indícios  de  TDAH  (Quebra  regras  e  preceitos  do  professor  ou  da  escola  sem motivação do professor e tem indícios de TDAH)

Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV