Co-Assembly of Cancer Drugs with Cyclo-HH Peptides: Insights from Simulations and Experiments.

Peptide-based nanomaterials can serve as promising drug delivery agents, facilitating the release of active pharmaceutical ingredients while reducing the risk of adverse reactions. We previously demonstrated that Cyclo-Histidine-Histidine (Cyclo-HH), co-assembled with cancer drug Epirubicin, zinc, and nitrate ions, can constitute an attractive drug delivery system, combining drug self-encapsulation, enhanced fluorescence, and the ability to transport the drug into cells. Here, we investigated both computationally and experimentally whether Cyclo-HH could co-assemble, in the presence of zinc and nitrate ions, with other cancer drugs with different physicochemical properties. Our studies indicated that Methotrexate, in addition to Epirubicin and its epimer Doxorubicin, and to a lesser extent Mitomycin-C and 5-Fluorouracil, have the capacity to co-assemble with Cyclo-HH, zinc, and nitrate ions, while a significantly lower propensity was observed for Cisplatin. Epirubicin, Doxorubicin, and Methorexate showed improved drug encapsulation and drug release properties, compared to Mitomycin-C and 5-Fluorouracil. We demonstrated the biocompatibility of the co-assembled systems, as well as their ability to intracellularly release the drugs, particularly for Epirubicin, Doxorubicin, and Methorexate. Zinc and nitrate were shown to be important in the co-assembly, coordinating with drugs and/or Cyclo-HH, thereby enabling drug-peptide as well as drug-drug interactions in successfully formed nanocarriers. The insights could be used in the future design of advanced cancer therapeutic systems with improved properties.

The educational and psychosocial needs of students with additional provisions during COVID-19 in Greece: Parents' perspectives against schools' crisis management.

BACKGROUND: The sudden breakdown of educational and care services following the COVID-19 outbreak caused severe implications to the educational and psychosocial well-being of students with additional needs. AIM: The present study investigates the perspectives of parents of students requiring additional provisions in relation to the schools' responsiveness against their children's educational and psychosocial needs during the COVID-19 pandemic, with a focus on (non-) applied inclusive and empowerment practices of parenthood. METHODS AND PROCEDURES: A sample of 125 parents in Greece filled out a self-reported questionnaire providing information on four main themes: school organisation in accordance with the COVID-19 measures; distance education; support on transition from quarantine and remote education back to school; and parental empowerment. OUTCOMES AND RESULTS: The data revealed that most of the participating parents felt poorly supported during the pandemic. The feeling of being left alone in supporting their children and in fully meeting their personal needs and emotions was also identified. The demographics of the participating parents with children with additional needs revealed an experiences mosaic in relation to the parents' level of education, the number of children who were present in their households, the children's gender as well as their level of school education (preschool- and primary school-aged or secondary school-aged pupils) and attendance of the school programme in regular or special schools. CONCLUSIONS AND IMPLICATIONS: Data suggest that regular and special schools in Greece, as orchestrated by the Ministry of Education, deployed practices that left students requiring additional provisions unsupported in relation to their educational and psychosocial needs while their parents felt disempowered during the whole period of the COVID-19 pandemic. A range of implications on a more effective support for families and their children with additional needs in alignment with the principles of inclusive education is detailed and discussed. WHAT THIS PAPER ADDS: The focus of research on the schools' responsiveness to the needs of students requiring additional provisions from the perspective of their parents is of critical importance as it may offer valuable insights pertaining to the school's inclusive policy practices and the promotion of empowering parent partnerships during crisis times. The knowledge gained by exploring parents' experiences will contribute significantly to inform modifications and changes in education delivery in crisis times so as school, as a social system, become more inclusive, supportive, and effective for pupils with additional needs. So far, little attention has been paid to the above-mentioned issues. In the current paper, the parents perspectives were explored through a self-reported questionnaire to reflect on the way schools responded to theirs and their children's educational and psychosocial needs during the COVID-19 pandemic. Most of the participating parents felt poorly supported. The feeling of being left alone in supporting their children and in fully meeting their personal needs and emotions was also identified. The demographics of the participating parents with children requiring additional provisions revealed an experiences mosaic in relation to the parents' level of education, the number of children who were present in their households, the children's gender as well as their level of school education (preschool and primary school or secondary school education) and attendance of the school programme in regular or special schools. A range of implications on a more effective support for families and their children with additional needs in alignment with the principles of inclusive education is detailed and discussed.

Peptide Self-Assembled Nanocarriers for Cancer Drug Delivery.

The design of novel cancer drug nanocarriers is critical in the framework of cancer therapeutics. Nanomaterials are gaining increased interest as cancer drug delivery systems. Self-assembling peptides constitute an emerging novel class of highly attractive nanomaterials with highly promising applications in drug delivery, as they can be used to facilitate drug release and/or stability while reducing side effects. Here, we provide a perspective on peptide self-assembled nanocarriers for cancer drug delivery and highlight the aspects of metal coordination, structure stabilization, and cyclization, as well as minimalism. We review particular challenges in nanomedicine design criteria and, finally, provide future perspectives on addressing a portion of the challenges via self-assembling peptide systems. We consider that the intrinsic advantages of such systems, along with the increasing progress in computational and experimental approaches for their study and design, could possibly lead to novel classes of single or multicomponent systems incorporating such materials for cancer drug delivery.

Quality of life and vocational education service quality in students with intellectual disability.

The aim of the study was to investigate the relation between subjective quality of life and quality of vocational education services from the view of students with intellectual disability who participate in public special vocational education schools in Greece. The level of quality of life and quality of special vocational education services was explored. The article presents a functional description of service quality in special vocational education and operationalizes quality of life for students with disability. Instruments were developed and adapted in line with the participatory research paradigm. Convenience sampling was used. Data was gathered from 131 students with intellectual disability. All measures showed good evidence of internal consistency and construct validity. The findings suggest relationship between quality of life and quality of special vocational education services received by students with intellectual disability. Low levels of self-determination are highlighted. Practical implications concerning the application of the instruments in special education settings as measures for the quality assessment and the evaluation of educational interventions are discussed.

Reinforcing adherence to lipid-lowering therapy after an acute coronary syndrome: A pragmatic randomized controlled trial.

BACKGROUND AND AIMS: Achieving the low-density lipoprotein cholesterol (LDL-C) goal following an acute coronary syndrome (ACS) is a milestone often missed due to suboptimal adherence to secondary prevention treatments. Whether improved adherence could result in reduced LDL-C levels is unclear. We aimed to evaluate whether an educational-motivational intervention increases long-term lipid-lowering therapy (LLT) adherence and LDL-C goal attainment rate among post-ACS patients. METHODS: IDEAL-LDL was a parallel, two-arm, single-center, pragmatic, investigator-initiated randomized controlled trial. Hospitalized patients for ACS were randomized to a physician-led integrated intervention consisting of an educational session at baseline, followed by regular motivational interviewing phone sessions or usual care. Co-primary outcomes were the LLT adherence (measured by Proportion of Days Covered (PDC); good adherence defined as PDC>80%), and LDL-C goal (<70 mg/dl or 50% reduction from baseline) achievement rate at one year. RESULTS: In total, 360 patients (mean age 62 years, 81% male) were randomized. Overall, good adherence was positively associated with LDL-C goal achievement rate at one year. Median PDC was higher in the intervention group than the control group [0.92 (IQR, 0.82-1.00) vs. 0.86 (0.62-0.98); p = 0.03] while the intervention group had increased odds of good adherence (odds ratio: 1.76 (95% confidence interval 1.02 to 2.62; p = 0.04). However, neither the LDL-C goal achievement rate (49.6% in the intervention vs. 44.9% in the control group; p = 0.49) nor clinical outcomes differed significantly between the two groups. CONCLUSIONS: Α multifaceted intervention improved LLT adherence in post-ACS patients without a significant difference in LDL-C goal attainment.

Experiences of workers with disabilities receiving supported employment services in Greece.

People with disabilities (PwDs) are under-represented in the workforce, especially during times of economic recession. Supported employment is recognized as an effective practice for promoting work inclusion of PwDs, including people with intellectual disabilities (IDs). This study aimed at exploring the experiences of workers with ID or mental health conditions who received supported employment services in Greece. Semi-structured interviews were conducted with nine workers with ID and five with mental health conditions. The thematic analysis revealed that emotional pressure was experienced by the participants with mental health conditions and those with ID during the job search and the adaptation period, respectively. On-the-job training was available for the participants with ID and assistance in finding suitable job opportunities was given to those with mental health conditions. All participants highlighted the importance of maintaining employment. The findings can inform efforts on developing employment services targeting social and work inclusion for PwDs.

Treatment practices and lipid profile of patients with acute coronary syndrome: results from a tertiary care hospital.

Background: Considering the increasing burden of cardiovascular risk factors and recent advances on the management of acute coronary syndromes (ACS), we studied the epidemiological characteristics and treatment strategies of patients presenting with ACS. We also evaluated the lipid profile and attainment of lipid goals in a 'real world' clinical setting.Methods: This was a substudy of IDEAL-LDL (Motivational interviewing to support low-density lipoprotein cholesterol (LDL-C) therapeutic goals and lipid-lowering therapy compliance in patients with acute coronary syndromes), a single-centre, prospective, randomised controlled trial. Baseline data from a total of 357 ACS patients were gathered using standardised methods.Results: Median age of patients was 60 years and 81.2% were males. Arterial hypertension and smoking were the most prevalent risk factors for coronary artery disease (CAD). Patients with ST-elevation myocardial infarction (STEMI) were heavier smokers, but were younger and exercised more compared to those with non-ST-elevation acute coronary syndrome (NSTE-ACS). Conversely, more NSTE-ACS patients had arterial hypertension, dyslipidaemia and diabetes mellitus. One-fifth of ACS patients was treated conservatively without a percutaneous coronary intervention (PCI). A combination of statin, dual antiplatelet therapy and beta-blockers were prescribed to 79.6% of patients upon discharge. A renin-angiotensin-aldosterone system inhibitor and a beta-blocker were prescribed to 67.3 and 91.8% of patients with LVEF ≤40%, respectively. Of patients with prior history of CAD, 63.1%, 71.4% and 58.3% received regularly statins, antiplatelets and beta-blocker treatment, respectively. Only 22.3% of these CAD patients had an optimal LDL-C of <70 mg/dl at admission.Conclusions: In hospitalised patients with ACS, management practices differed by ACS type and discharge medication was, mostly, in line with the latest guidelines. However, medication adherence and lipid lowering goals of secondary CAD prevention were largely unachieved.

Challenges for the labor market: 2 complementary approaches to premature cessation of occupational activity.

OBJECTIVES: Current demographic trends, such as society aging, the spreading of chronic diseases, as well as early retirement choices, lead to the dwindling labor market population. Taking into consideration the foregoing tendencies and their consequences, the issue of the shrinking labor force resources seems to be the most important challenge for the labor market. In response to it, this paper identifies individual and institutional causes of withdrawal from the labor market, and explores the views of Polish stakeholders on existing strategies for the occupational re-integration of persons with chronic diseases (PwCDs). MATERIAL AND METHODS: Polish results of 2 European projects: "Participation to Healthy Workplaces and Inclusive Strategies in the Work Sector" (the PATHWAYS project) and "The Collaborative Research on Aging in Europe" (COURAGE in Europe) complemented each other. The cross-sectional population data and data from stakeholders' interviews were used. RESULTS: The authors identified several causes which could encourage people to withdraw from the labor market before attaining the official retirement age at 3 different levels: individual, occupational, and institutional. Although research has shown that the macro-level situation is crucial to staying occupationally active, in Poland stakeholders have reported the lack of effective coordination in the implementation of policies for the occupational re-integration of PwCDs. CONCLUSIONS: A decision to cease work prematurely reflects a combination of many different factors, such as individual determinates, work characteristics, personal convictions, and systemic solutions. The study demonstrated that, despite the awareness of the dwindling resources of labor force, the employment-related challenges faced by PwCDs as well as people who are close to the retirement age remain unaddressed. Int J Occup Med Environ Health. 2019;32(5):695-721.

Motivational interviewing to support LDL-C therapeutic goals and lipid-lowering therapy compliance in patients with acute coronary syndromes (IDEAL-LDL) study: rationale and design.

BACKGROUND: Achieving low-density lipoprotein cholesterol (LDL-C) target levels after an acute coronary syndrome (ACS) is of paramount importance, and is often burdened by undertreatment and medication or lifestyle non-adherence issues. OBJECTIVE: We examined the effect of a patient-centered, physician-led motivational intervention following ACS on relevant secondary prevention aspects. METHODS-DESIGN: The IDEAL-LDL is a single-center, randomized controlled clinical trial, conducted among patients hospitalized due to an ACS. Following discharge, all patients undergo a baseline assessment of lipid profile. Patients in the intervention group receive an in-person educational session and an informative leaflet, and also undergo two phone-based, motivational interviewing sessions at 1 and 6 months. These interventions emphasize on LDL-C goals, adherence to lipid-lowering medication, and healthy dietary-lifestyle habits, and are not provided to patients in the control group, who receive usual care. At 12 months after each patient's discharge, an in-person interview and lipid profile reassessment are performed. The primary outcomes are the assessment of LDL-C goal achievement (<70 mg/dL or >50% reduction from baseline levels) from baseline to 1 year and changes in medication adherence. Secondary outcomes relate to the incidence of the composite outcome of cardiovascular death, nonfatal myocardial infarction/stroke, need for myocardial revascularization, and recurrent hospitalization during the follow-up period. DISCUSSION: This paper describes the protocol, design, and rationale for key methodology for an ongoing clinical trial featuring a simple and feasible intervention. Similar adherence efficacy trials have not led to sufficient improvements, and there remains a gap regarding how adherence interventions should be implemented into clinical care.

Identifying the Employment Needs of People With Chronic Health Conditions in Europe.

OBJECTIVES: The main goal of this study was to compare the employment needs experienced by people with different chronic health conditions and in different welfare systems. METHODS: A total of 688 participants with six chronic health conditions were collected in nine countries representing four welfare systems in Europe (Continental, Mediterranean, Postcommunist, and Scandinavian). RESULTS: Raising awareness of what is to live with a chronic health condition in the workplace was the area perceived as more favorable. The types of employment needs were different across the social welfare systems but did not vary among the different chronic health conditions groups. CONCLUSION: Although diverse, there appear to be some common needs transversal to the working experience of people with chronic health problems. Actions to improve the employability of people with chronic health conditions should be tailored to each welfare system.

Policy Guidelines for Effective Inclusion and Reintegration of People with Chronic Diseases in the Workplace: National and European Perspectives.

The increasing prevalence of chronic diseases among the European working age population, as well as the implications for the individual and societal level, underline the need for policy guidelines targeting the effective inclusion of persons with chronic diseases in the workplace. The aim of the present paper was to explore the perspectives of European and National-level stakeholders on existing strategies for work re-integration of persons with chronic diseases, and to provide policy guidelines. A highly-structured interview protocol was distributed to 58 National level stakeholders (policy makers, professionals and employers) from seven European countries. Additionally, 20 European organizations concerned with health-related issues and employment completed an online survey. The findings reveal that employment-related challenges remain largely unaddressed. Both national and European stakeholders considered the existing legislative frameworks inadequate and appraised the co-ordination for the implementation of employment re-integration policies as ineffective. Policies targeting at work re-integration of persons with chronic diseases at European and national level should focus on consistent cooperation among all key stakeholders, awareness raising to staff and management, dissemination of effective strategies, developing research and evaluation standards and establishing monitoring systems on inclusive labour markets.

What Persons with Chronic Health Conditions Need to Maintain or Return to Work-Results of an Online-Survey in Seven European Countries.

Chronic health conditions represent the major share of the disease burden in Europe and have a significant impact on work. This study aims to: (1) identify factors that have a negative or positive impact on the work lives of persons with chronic health conditions; (2) explore the needs of these persons to maintain a job or return to work and (3) compare these results with respect to these persons' occupational status. An online survey was performed in seven European countries. Open-ended survey questions were analyzed using qualitative methods. In total, 487 participants with six chronic health conditions participated. The majority of participants named work-related aspects (such as career development, stress at the workplace, work structure and schedule as well as workload), support of others and attitudes of others as being the factors positively and negatively impact their work lives the most. Our study shed light on the importance of changing the attitudes of supervisors and co-workers to counteract stigmatization of persons with chronic health conditions in the workplace. In conclusion, this study provides a basis for developing new strategies of integration and reintegration at work for persons with chronic health conditions in European countries.

Effectiveness of Integration and Re-Integration into Work Strategies for Persons with Chronic Conditions: A Systematic Review of European Strategies.

Due to low employment rates associated to chronic conditions in Europe, it is essential to foster effective integration and re-integration into work strategies. The objective of this systematic review is to summarize the evidence on the effectiveness of strategies for integration and re-integration to work for persons with chronic diseases or with musculoskeletal disorders, implemented in Europe in the past five years. A systematic search was conducted in MedLine, PsycINFO, CDR-HTA, CDR-DARE and Cochrane Systematic Reviews. Overall, 32 relevant publications were identified. Of these, 21 were considered eligible after a methodological assessment and included. Positive changes in employment status, return to work and sick leave outcomes were achieved with graded sickness-absence certificates, part-time sick leave, early ergonomic interventions for back pain, disability evaluation followed by information and advice, and with multidisciplinary, coordinated and tailored return to work interventions. Additionally, a positive association between the co-existence of active labour market policies to promote employment and passive support measures (e.g., pensions or benefits) and the probability of finding a job was observed. Research on the evaluation of the effectiveness of strategies targeting integration and re-integration into work for persons with chronic health conditions needs, however, to be improved and strengthened.

Motivational beliefs, cognitive engagement, and achievement in language and mathematics in elementary school children.

The contextual differences in the patterns of relations among various motivational, cognitive, and metacognitive components of self-regulated learning and performance in two key curriculum subject areas, language and mathematics, were examined in a sample of 263 Greek primary school children of fifth- and sixth-grade classrooms. Age and gender differences were also investigated. Students were asked to complete the Motivated Strategies for Learning Questionnaire (Pintrich & De Groot, 1990 ), which comprised five factors: (a) Self-efficacy, (b) Intrinsic Value, (c) Test Anxiety, (d) Cognitive Strategy Use, and (e) Self-regulation Strategies. They responded to the statements of the questionnaire on a 7-point Likert scale in terms of their behaviour in mathematics and language classes, respectively. Moreover, their teachers were asked to evaluate each of their students' academic achievement in Greek language and mathematics on a 1- to 20-point comparative scale in relation to the rest of the class. The results of the study indicated very few differences in the pattern of relations among self-regulated components within and across the two subject areas and at the same time revealed a context-specific character of self-regulated components at a mean level differences. Further, the current study (a) confirmed the mediatory role of strategies in the motivation-performance relation, (b) stressed the differential role of cognitive and regulatory strategies in predicting performance in subject areas that differ in their structural characteristics of the content, and (c) pointed out the key motivational role of self-efficacy. In fact, self-efficacy proved the most significant predictor not only of performance but of cognitive and regulatory strategy use as well. Gender differences in motivation and strategy use were not reported, while motivation was found to vary mainly with age. The usefulness of these findings for promoting greater clarity among motivational and metacognitive frameworks and ideas for future research are discussed. Cette étude porte sur les différences contextuelles dans les patrons relationnels entre les diverses composantes motivationnelle, cognitive et métacognitive de l'apprentissage et de la performance auto-régulés dans deux domaines d'étude clé du programme, soit la langue et les mathématiques. Ces différences contextuelles ont été examinées dans un échantillon de 263 d'enfants d'une école primaire grecque (of) en cinquième et sixième année. Les différences sexuelles et les différences d'âge ont été aussi étudiées. Les élèves ont été priés de compléter le «Motivated Strategies for Learning Questionnaire¼ (Pintrich & De Groot, 1990 ) qui comprend cinq facteurs: (a) l'auto-efficacité, (b) la valeur intrinsèque, (c) un test d'anxiété, (d) l'utilisation d'une stratégie cognitive et (e) les stratégies d'auto-régulation. Ils ont répondu aux énoncés du questionnaire sur une échelle de type Likert à 7 points en termes de leur comportement en classe de langue et en classe de mathématiques séparément. De plus, les enseignants ont été priés d'évaluer chaque résultat de leurs élèves dans la langue grecque et en mathématique sur une échelle allant de 1 à 20 points en comparaison au reste de la classe. Les résultats de l'étude ont indiqué très peu de différences dans les patrons relationnels entre les composantes auto-régulées à l'intérieur et entre les domaines d'étude. En même temps, les résultats ont révélé un caractère contextuel spécifique des composantes auto-regulées. De plus, la présente étude (a) a confirmé le rôle médiateur des stratégies dans la relation motivation-performance, (b) a souligné le rôle différé des stratégies cognitive et régulatoire dans la prédiction de la performance dans les domaines d'étude qui diffèrent dans leurs caractéristiques structurelles du contenu et (c) a souligné le rôle motivationnel clé de l'auto-efficacité. En effet, l'auto-efficacité s'est avérée être le prédicteur le plus significatif non seulement de la performance mais aussi de l'utilisation d'une stratégie cognitive et régulatoire. Des différences sexuelles dans la motivation et dans l'utilisation d'une stratégie n'ont pas été rapportées alors qu'il s'est avéré que la motivation variait principalement en fonction de l'âge. L'utilité de ces résultats pour la promotion d'une grande clarté entre les cadres motivationnel et métacognitif et les idées pour les études futures sont discutées. Se examinó, en una muestra de 263 niños griegos de quinto y sexto años de la escuela primaria, las diferencias contextuales en las pautas con las que se dan las relaciones entre varios componentes motivacionales, cognitivos y meta cognitivos del aprendizaje autorregulado y el desempeño en dos áreas clave del currículo, lenguaje y matemáticas. También se investigó las diferencias de edad y género. Se pidió a los alumnos que respondieran el Cuestionario de Estrategias Motivadas para el Aprendizaje (Pintrich & De Groot, 1990 ), compuesto por cinco factores: (a) Auto eficacia, (b) Valor Intrínseco, (c) Ansiedad ante los Exámenes, (d) Empleo de Estrategias Cognitivas, y (e) Estrategias Autorreguladas. Respondieron a los enunciados del cuestionario sobre una escala Likert de 7 puntos en términos de su conducta en las clases de matemáticas y lenguaje por separado. Es más, se pidió a sus profesores que evaluaran el desempeño de cada uno de sus estudiantes en Lenguaje Griego y Matemáticas de acuerdo con una escala comparativa de 1 a 20 puntos, en relación con el resto del grupo escolar. Los resultados del estudio indicaron pocas diferencias en la pauta que describen las relaciones entre los componentes de autorregulación al interior de y entre ambas áreas de estudio y, al mismo tiempo, revelaron un carácter específico del contexto de los componentes de la autorregulación con diferencias en el nivel medio. Más aún, el presente estudio (a) confirmó el papel de mediador que desempeñan las estrategias sobre la relación motivación-desempeño, (b) acentuó el papel diferencial de las estrategias cognitiva y reguladora al predecir el desempeño en áreas de estudio que difieren en las características estructurales de su contenido, y (c) señaló el papel motivacional clave que desempeña la auto eficacia. De hecho, la auto eficacia predijo de manera más significativa no sólo el desempeño, sino también el uso de la estrategia cognitiva y reguladora. No hubo diferencias de género respecto a la motivación y al uso de la estrategia, aunque se encontró que la motivación varía principalmente con la edad. Se discute la utilidad de estos hallazgos para aclarar los referentes motivacionales y meta cognitivos y promover ideas para investigaciones futuras.