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Background: A type 3 medication review (MR3) is a patient-centred medication service primarily provided by pharmacists and is presently employed routinely in several countries. In this process, pharmacists interview patients and collaborate with the treating physician to optimize the patient's pharmacotherapy, taking into account the patient's medication history and other medical data including laboratory values. The need to maintain the quality of such interventions during and after their initial implementation cannot be overstated. Aim: The objective of this study was to refine and assess a scoring table to evaluate the quality of MR3 conducted in Belgian community pharmacies. Methods: The comprehensive quality of MR3s was assessed by scoring its various components using a previously developed scoring table, called BRANT-MERQS, Brussels Antwerp Medication Review Quality Score. MR3s were analysed from an implementation study with patients suffering from rheumatoid arthritis (RA, subproject 1) and type 2 diabetes mellitus (T2DM, subproject 2). Additional information was obtained during a telephone call with a subset of participating pharmacists of subproject 1 who finalized their first MR3. Results: In subproject 1, a total of 21 MR3s of patients with RA were examined. The assessment showed favourable scores for elements such as a well-organized medication schedule, treatment adherence, and the elaboration of specific interventions. However, certain other quality criteria posed challenges in the evaluation, for example, the use of simple and understandable language. Pharmacists faced time constraints, and elderly general practitioners (GPs) displayed limited enthusiasm, which were notable barriers observed for this subproject. In the context of subproject 2 that investigated 41 MR3s in patients with T2DM, the quality criteria of interaction between pharmacist and GP, and used sources and tools received high scores. However, there was still room for improvement, especially in areas such as accurate dosing, handling kidney function, QT prolongation, correctly associating laboratory values with relevant drugs and medical conditions, and optimisation of medication schedules for patients. Conclusion: This study demonstrated the feasibility of MR3 quality assessment through a scoring system. However, it also unveiled the tool's current imperfections and highlighted the ongoing need for refinement, something expected of a new service in an implementation phase. [ABSTRACT FROM AUTHOR]

Informal learning environments (ILEs) like Fablabs and Makerspaces have potential to facilitate development of STEM skills. However, these environments might be difficult for teachers to adopt in their teaching because of teaching approaches grounded in constructionism where the role of the teacher changes from a transmissive instructor to an active co-creator, and using high-tech equipment not normally found in schools. The aim is to investigate teachers' self-efficacy and perceived role when teaching STEM in Fablabs and Makerspaces. This is investigated related to teaching in ILEs and using high-tech equipment. The study was conducted in two countries/regions, Flanders (Belgium) and Sweden We also compare differences between teachers depending on nationality, gender, and years of teaching experience. A total of 347 secondary school teachers completed an online survey. Quantitative analyses was used for all questions in the survey, except one open-ended question, which was analysed through inductive thematic coding. The teachers reported moderate self-efficacy for teaching in ILEs , and low self-efficacy for using high-tech equipment. Some teachers described themselves as having active roles as a coach or as co-learner during visits with their students. Others saw themselves as having a passive role. Many teachers did not know what kind of role to take. The teachers who perceived an active role as a teacher in high-tech ILEsreported higher self-efficacy to teach in these environments than other teachers. This study shows that a constructionist approach to teaching is important if teachers are to develop self-efficacy to teach in high-techILEs. Thus, developing teacher practices in line with constructionism in relation to teaching in high-techILEsis imperative, in teacher education. The results also highlight that staff in Fablabs and Makerspaces are important for handling high-tech equipment. Hence, collaboration between staff in ILEs and teachers is of importance. [ABSTRACT FROM AUTHOR]

It should be the ultimate goal of any theory of evolution to delineate the contours of an integrative system to answer the question: How does life (in all its complexity) evolve (which can be called mega‐evolution)? But how to plausibly define 'life'? My answer (1994–2023) is: 'life' sounds like a noun, but denotes an activity, and thus is a verb. Life (L) denotes nothing else than the total sum (∑) of all acts of communication (transfer of information) (C) executed by any type of senders–receivers at all their levels (up to at least 15) of compartmental organization: L = ∑C. The 'communicating compartment' is better suited to serve as the universal unit of structure, function and evolution than the cell, the smallest such unit. By paying as much importance to communication activity as to the Central Dogma of molecular biology, a wealth of new insights unfold. The major ones are as follows. (1) Living compartments have not only a genetic memory (DNA), but also a still enigmatic cognitive and an electrical memory system (and thus a triple memory system). (2) Complex compartments can have up to three types of progeny: genetic descendants/children, pupils/learners and electricians. (3) Of particular importance to adaptation, any act of communication is a problem‐solving act because all messages need to be decoded. Hence through problem‐solving that precedes selection, life itself is the driving force of its own evolution (a very clever but counterintuitive and unexpected logical deduction). Perhaps, this is the 'vital force' philosopher and Nobel laureate (in 1927) Henri Bergson searched for but did not find. [ABSTRACT FROM AUTHOR]

Background: Although the importance of context in implementation science is not disputed, knowledge about the actual impact of external context variables on implementation processes remains rather fragmented. Current frameworks, models, and studies merely describe macro-level barriers and facilitators, without acknowledging their dynamic character and how they impact and steer implementation. Including organizational theories in implementation frameworks could be a way of tackling this problem. In this study, we therefore investigate how organizational theories can contribute to our understanding of the ways in which external context variables shape implementation processes. We use the implementation process of goal-oriented primary care in Belgium as a case. Methods: A qualitative study using in-depth semi-structured interviews was conducted with actors from a variety of primary care organizations. Data was collected and analyzed with an iterative approach. We assessed the potential of four organizational theories to enrich our understanding of the impact of external context variables on implementation processes. The organizational theories assessed are as follows: institutional theory, resource dependency theory, network theory, and contingency theory. Data analysis was based on a combination of inductive and deductive thematic analysis techniques using NVivo 12. Results: Institutional theory helps to understand mechanisms that steer and facilitate the implementation of goal-oriented care through regulatory and policy measures. For example, the Flemish government issued policy for facilitating more integrated, person-centered care by means of newly created institutions, incentives, expectations, and other regulatory factors. The three other organizational theories describe both counteracting or reinforcing mechanisms. The financial system hampers interprofessional collaboration, which is key for GOC. Networks between primary care providers and health and/or social care organizations on the one hand facilitate GOC, while on the other hand, technology to support interprofessional collaboration is lacking. Contingent variables such as the aging population and increasing workload and complexity within primary care create circumstances in which GOC is presented as a possible answer. Conclusions: Insights and propositions that derive from organizational theories can be utilized to expand our knowledge on how external context variables affect implementation processes. These insights can be combined with or integrated into existing implementation frameworks and models to increase their explanatory power. [ABSTRACT FROM AUTHOR]

Lean patients with NAFLD may develop cardiac complications independently of pre-existent metabolic disruptions and comorbidities. To address the underlying mechanisms independent of the development of obesity, we used a murine model of hepatic mitochondrial deficiency. The liver-heart axis was studied as these mice develop microvesicular steatosis without obesity. Our results unveil a sex-dependent phenotypic remodeling beyond liver damage. Males, more than females, show fasting hypoglycemia and increased insulin sensitivity. They exhibit diastolic dysfunction, remodeling of the circulating lipoproteins and cardiac lipidome. Conversely, females do not manifest cardiac dysfunction but exhibit cardiometabolic impairments supported by impaired mitochondrial integrity and β-oxidation, remodeling of circulating lipoproteins and intracardiac accumulation of deleterious triglycerides. This study underscores metabolic defects in the liver resulting in significant sex-dependent cardiac abnormalities independent of obesity. This experimental model may prove useful to better understand the sex-related variability, notably in the heart, involved in the progression of lean-NAFLD. A genetic mouse model of lean-NAFLD reveals that male exhibit a more severe hepatic phenotype with increased macrophage infiltration, FGF21 concentration and sustained hypoglycemia associated with cardiac diastolic dysfunction. [ABSTRACT FROM AUTHOR]

Background: Medication review is a multifaceted service aimed at optimizing the use of medicines and enhancing the health outcomes of patients. Due to its complexity, it is crucial to clearly describe the service, its variants, and its components to avoid confusion and ensure a better understanding of medication review among healthcare providers. Aim: This study aims to bring clarity to the origins, definitions, abbreviations, and types of medication reviews, together with the primary criteria that delineate key features of this service. Method: A narrative review approach was employed to clarify the diverse terminology associated with "medication review" services. Relevant references were initially identified through searches on PubMed and Google Scholar, complementing the existing literature known to the authors. Results: The study uncovers a complicated and sometimes convoluted history of "medication review" in different regions around the world. The initial optimization of medicine use had an economic purpose before evolving subsequently into a more patient-oriented approach. A selection of abbreviations, definitions, and types were outlined to enhance the understanding of the service. Conclusions: The study underscores the urgent need for comprehensive information and standardization regarding the content and quality of the services, collectively referred to as "medication review". [ABSTRACT FROM AUTHOR]

Background: A six year collaboration between academics, community pharmacists and informaticians, led to the development of nine guidelines for a clinical decision support system, enhancing community pharmacists' ability to address drug-related problems and improve care. Aim: The objective of this study was to assess the effectiveness of clinical decision support system rules in enhancing medication management within the community pharmacy setting. This was achieved through retrospective monitoring of real-world usage and measuring the pharmacotherapeutic impact of the rules. Method: In 2019, a retrospective observational evaluation appraised the acceptance rate of the clinical decision support system components in 490 Belgian pharmacies. Among these, 51 pharmacies underwent a longitudinal analysis involving (i) co-prescription of methotrexate and folic acid, (ii) gastroprotection with non-steroidal anti-inflammatory drugs, and (iii) drug combinations causing QT prolongation. The study period spanned one year pre-launch, one year post-launch, and two years post-launch. Results: Of the targeted pharmacies, 80% used 7 of the 9 rules. After four years, methotrexate-folic acid co-prescription increased 4%, reaching 79.8%. Gastroprotection improved by 3% among older patients and 7.47% in younger individuals (< 70 year) with multiple risk factors. The QT prolongation rules faced implementation difficulties. Conclusion: Pharmacists' acceptance of the developed rules was high and coincided with a decline in drug-related problems, holding potential public health impact. This real-world data can inform the future implementation of such systems, as it demonstrated the need for more detailed data-gathering and more intensive training of pharmacists in the handling of more complex problems such as QT prolongation. [ABSTRACT FROM AUTHOR]

Background: Medication reviews are a structured evaluation of a patient's pharmacotherapy with the aim of optimizing medicines use and improving health outcomes. This entails detecting drug related problems and recommending interventions. A high level of quality is essential for the successful implementation of this service in community pharmacies but currently there is no instrument or tool to assess that overall quality. Aim: This study investigated the development of quality criteria of type 3 medication reviews (MR3s). Methods: After surveying the literature, an electronic questionnaire was developed to gather information about quality criteria for MR3. This survey, in Dutch, was distributed electronically. Four groups were queried: 1) pharmacists, mainly working in the Netherlands, involved in practice research and contacted through the PRISMA (Practice Research In Collaboration With Pharmacists) foundation, 2) Belgian pharmacy academics and pharmacists active in professional associations (APA), 3) Belgian pharmacists trained in medication review (MR) by the Royal Pharmacists Association of Antwerp (KAVA) and 4) Belgian pharmacy students. The survey included 57 criteria, divided into eight domains, which were ranked according to their importance by the participants. The results were analyzed statistically using the nonparametric Kruskal-Wallis test. Results: The survey was completed by 95 participants, including 42 PRISMA pharmacists, 19 APA pharmacists, 18 KAVA pharmacists and 16 pharmacy students. Opinions from participants from the different groups overlapped significantly. The use of simple and understandable language in the conversation with the patient was considered essential by the majority. Discussing the usefulness and purpose of a MR3 with the patient was also rated highly by all groups. Differences of opinion were present in aspects about laboratory values, the use of specific tools, and reporting to and consultationwith the treating physician. The participants themselves formulated a limited number of additional assessment criteria. Conclusion: There was widespread agreement on the hierarchy of the quality assessment criteria for MR3s. Minor differences were related to the experience of the participants. With these results and a small number of suggested extra criteria, a quality assessment instrument for MR3 can be created. [ABSTRACT FROM AUTHOR]

Background: Medication reviews are a structured critical evaluation of a patient's pharmacotherapy, carried out by a healthcare professional, but are not yet a routine pharmaceutical service in Belgium. A pilot project to initiate an advanced medication review (= type 3 medication review) in community pharmacies was set up by the Royal Pharmacists' Association of Antwerp. Aim: To investigate the experiences and opinions of patients who participated in this pilot project. Method: Qualitative study through semi-structured interviews with participating patients. Results: Seventeen patients from six different pharmacies were interviewed. The medication review process with the pharmacist was perceived as positive and instructive by fifteen interviewees. The extra attention that the patient received was highly appreciated. However, the interviews revealed that patients did not fully understand the purpose and structure of this new service or were aware of the subsequent contact and feedback with the general practitioner. Medication reviews in the home setting put patients more at ease, were highly appreciated, and enabled also to address practical problems such as drug dosing or storage requirements. Conclusion: This qualitative study analysed patients' experiences during a pilot project on the implementation of type 3 medication review. Although most patients were enthusiastic about this new service, a lack of patients' understanding of the whole process was also observed. Therefore, better communication to patients by pharmacists and general practitioners about the goals and components of this type of medication review is needed, with the added benefit of increased efficiency. [ABSTRACT FROM AUTHOR]

The awareness that many problems in our society are interdisciplinary in nature and require the integration of multiple STEM (Science, Technology, Engineering, Mathematics) concepts to solve them has given rise to a new instructional approach, called "integrated STEM education". Integrated STEM education aims to remove the barriers from the STEM fields and has the potential to increase students' interest and motivation for learning, as well as to lead to improved achievement. It is important to assess the effectiveness of educational STEM initiatives in terms of students' integrating ability, but to date, no such instruments are available. This study provides a definition of "integrating ability" and establishes a framework for understanding its components. Based on this definition and framework, a multiple-choice instrument for testing integrated physics and mathematics in the ninth grade (IPM9) was developed and validated. The definition and framework for integrating ability and the construction guidelines for an integrated test, can be used by researchers to assess students' ability to integrate STEM subjects. [ABSTRACT FROM AUTHOR]

Fatty acids (FAs) rapidly and efficiently reduce cardiac glucose uptake in the Randle cycle or glucose-FA cycle. This fine-tuned physiological regulation is critical to allow optimal substrate allocation during fasted and fed states. However, the mechanisms involved in the direct FA-mediated control of glucose transport have not been totally elucidated yet. We previously reported that leucine and ketone bodies, other cardiac substrates, impair glucose uptake by increasing global protein acetylation from acetyl- CoA. As FAs generate acetyl-CoA as well, we postulated that protein acetylation is enhanced by FAs and participates in their inhibitory action on cardiac glucose uptake. Here, we demonstrated that both palmitate and oleate promoted a rapid increase in protein acetylation in primary cultured adult rat cardiomyocytes, which correlated with an inhibition of insulin-stimulated glucose uptake. This glucose absorption deficit was caused by an impairment in the translocation of vesicles containing the glucose transporter GLUT4 to the plasma membrane, although insulin signaling remained unaffected. Interestingly, pharmacological inhibition of lysine acetyltransferases (KATs) prevented this increase in protein acetylation and glucose uptake inhibition induced by FAs. Similarly, FA-mediated inhibition of insulin-stimulated glucose uptake could be prevented by KAT inhibitors in perfused hearts. To summarize, enhanced protein acetylation can be considered as an early event in the FA-induced inhibition of glucose transport in the heart, explaining part of the Randle cycle. [ABSTRACT FROM AUTHOR]

Implementing Comprehensive Medication Management (CMM) services uncovered the importance of the totality of the patient's perspective in this process. The holistic approach takes into account the physical, mental and emotional well-being of individuals, as well as their socioeconomic circumstances. The aim of this study was to characterize the scientific evidence associated with CMM services that included this holistic approach. A scoping review was conducted based on Arksey and O'Malley's method. Searches were performed in Google Scholar for papers published between 2010 and 2020 in English, Spanish and Portuguese. Study design, health contexts, sample of patients, results obtained, barriers and facilitators, and the integration of a holistic approach were determined. Two hundred and eighteen papers were evaluated, most of which focused on the implementation of this service through prospective observational studies. A minority of studies reported on a holistic approach, a smaller number examined the effect of social determinants of health, the patient's medication experiences and the pharmacotherapy outcomes from the patient's perspective. Despite the progress achieved, most of the referents do not yet reflect a broader view of the patient's life situation and its relationship to pharmacotherapy and the ways in which the pharmacist implements holistic elements to solve or prevent drug-related problems. [ABSTRACT FROM AUTHOR]

Aims and objectives: Gaining insight in how people living with chronic conditions experience primary healthcare within their informal network. Background: The primary healthcare system is challenged by the increasing number of people living with chronic conditions. To strengthen chronic care management, literature and policy plans point to a person‐centred approach of care (PCC). A first step to identify an appropriate strategy to implement PCC is to gain more insight into the care experiences of these people and their informal caregivers. Design: A phenomenological‐hermeneutical philosophy is used. The study is in line with the Consolidated Criteria for Reporting Qualitative Research Guidelines (COREQ). Method: In‐depth, semi‐structured interviews with people living with chronic conditions and informal caregiver dyads (PCDs) (n = 16; 32 individuals) were conducted. An open‐ended interview guide was used to elaborate on the PCDs' experiences regarding primary care. A purposive, maximal variation sampling was applied to recruit the participants. Results: Based on sixteen PCDs' reflections, ten themes were identified presenting their experiences with primary care and described quality care as listening and giving attention to what people with chronic conditions want, to what they strive for, and above all to promote their autonomy in a context wherein they are supported by a team of formal caregivers, family and friends. Conclusion: To meet the PCDs' needs, self‐management should be addressed in an interprofessional environment in which the PCD is an important partner. The findings may facilitate a shift to encourage PCDs in their strengths by enabling them to share their personal goals and by working towards meaningful activities in team collaboration. Relevance to clinical practice: Three strategies—self‐management support, goal‐oriented care, and interprofessional collaboration—have been suggested to improve the PCDs' primary care experiences. These strategies could guide nursing practice in using more and improve high‐quality nursing care. [ABSTRACT FROM AUTHOR]

Background: To address the many challenges health systems and communities face, primary care is constantly searching for new strategies to improve quality of care. One of the strategies is to focus on patients' personal goals to direct the care process. To adopt an explicit focus on patients' personal goals, actions at different levels are required. As a first step in this process, this study aims to explore the experiences of primary care stakeholders (i.e., scholars, primary care providers, and policy makers) and develop a comprehensive understanding on the idea 'putting patients' goals first'. This will help to formulate suggestions about what these actions should include. Method: In this study, 41 primary care stakeholders participating in six focus groups between January 2020 and September 2020, were recruited via maximal variation purposive sampling. Data collection was done through an open-ended semi-structured interview guide. Focus groups were audio-recorded, transcribed verbatim, and analyzed following a phenomenological-hermeneutical philosophy of Lindseth and Norberg. Results: All participants expressed a strong fundamental belief for putting patients' personal goals first. The primary care providers shared that they created space for patients' personal goals by letting them talk about their values and stories. They reported to integrate their medical expertise with patients' personal goals in order to develop a balanced relationship. In this context, they also talked about the importance of taking into account the perspectives of patients' significant others. Primary care providers also talked about how they used patients' personal goals as a guide in interprofessional collaboration. Scholars denoted that (future) care providers need more training to acquire competencies to discuss patients' personal goals. The providers and policy makers talked about organizational limitations in terms of time restrictions and the lack of registration systems to support a workflow oriented towards patients' personal goals. Conclusions: This study can be used to support the coherence of the development of different actions and strategies to get primary care stakeholders fully on board to support the adoption of patients' personal goals in care delivery at different levels. However, models of practice and policy plans are needed to work towards a person-centered integrated system. [ABSTRACT FROM AUTHOR]

Background: Coping with a chronic disease can be really challenging. Self-management represents a promising strategy to improve daily life experiences. The role of primary healthcare professionals cannot be underestimated in supporting self-management. Due to a shortage of theory, implementation of self-management support is hindered in primary care practice. The aim of this study is to create a conceptual model for self-management support by analysing patients’ care experiences towards self-management support. Methods: An explorative-descriptive qualitative study was conducted in Flanders, Belgium. Semi-structured interviews were performed with 16 patients and their informal caregiver (dyads) using a purposive sampling strategy and processed by an inductive content analysis, according to Graneheim and Lundman. Results: Interviews revealed in-depth insights into patients’ care experiences. A conceptual model was developed for primary care practice, including five fundamental tasks for healthcare professionals - Supporting, Involving, Listening, Coordinating and Questioning (SILCQ) – contributing to the support of self-management of chronic patients. Conclusions: This qualitative paper emphasises the use of the SILCQ-model to develop optimal roadmaps and hands-on toolkits for healthcare professionals to support self-management. The model needs to be further explored by all stakeholders to support the development of self-management interventions in primary care practice. [ABSTRACT FROM AUTHOR]

The "leaky pipeline" with regard to students' engagement in Science, Technology, Engineering, and Mathematics (STEM) has triggered extensive research to understand and prevent students dropping out from STEM. To boost enrolment and interest in STEM fields, integrated STEM (iSTEM) education could be harnessed by providing students with relevant challenges. This study investigated (1) the evolution of affective outcomes regarding science and mathematics over time in traditional education, (2) the impact of an iSTEM curriculum on affective outcomes with regard to science and mathematics, and (3) the differential effectiveness of the iSTEM curriculum regarding student characteristics. Therefore, an iSTEM intervention was developed and evaluated over the course of 2 years. In total, 859 grade 9 students, distributed across 39 different Belgian schools, participated in the longitudinal study. The results of multilevel analyses show that students' attitudes, motivation, and self-efficacy with regard to science and mathematics tend to become less positive over time in traditional education. On the other hand, iSTEM education had positive effects on attitudes towards science and mathematics. However, negative results were observed with regard to motivation and self-efficacy outcomes. In addition, intervention effects differed for boys and girls and for students at different socioeconomic status levels. Our results indicate that iSTEM has the potential to improve students' attitudes towards STEM, but that we should be careful with regard to the implementation of this approach in terms of student motivation and self-efficacy. [ABSTRACT FROM AUTHOR]

Background: Increased opioid prescribing has raised concern, as the benefits of pain relief not always outweigh the risks. Acute and chronic pain is often treated in a primary care out-of-hours (OOH) setting. This setting may be a driver of opioid use but the extent to which opioids are prescribed OOH is unknown. We aimed to investigate weak and strong opioid prescribing at OOH primary care services (PCS) in Flanders (Northern, Dutch-speaking part of Belgium) and the Netherlands between 2015 and 2019. Methods: We performed a retrospective cross sectional study using data from routine electronic health records of OOH-PCSs in Flanders and the Netherlands (2015–2019). Our primary outcome was the opioid prescribing rate per 1000 OOH-contacts per year, in total and for strong (morphine, hydromorphone, oxycodone, oxycodone and naloxone, fentanyl, tapentadol, and buprenorphine and weak opioids (codeine combinations and tramadol and combinations) and type of opioids separately. Results: Opioids were prescriped in approximately 2.5% of OOH-contacts in both Flanders and the Netherlands. In Flanders, OOH opioid prescribing went from 2.4% in 2015 to 2.1% in 2017 and then increased to 2.3% in 2019. In the Netherlands, opioid prescribing increased from 1.9% of OOH-contacts in 2015 to 2.4% in 2017 and slightly decreased thereafter to 2.1% of OOH-contacts. In 2019, in Flanders, strong opioids were prescribed in 8% of the OOH-contacts with an opioid prescription. In the Netherlands a strong opioid was prescribed in 57% of these OOH-contacts. Two thirds of strong opioids prescriptions in Flanders OOH were issued for patients over 75, in the Netherlands one third was prescribed to this age group. Conclusion: We observed large differences in strong opioid prescribing at OOH-PCSs between Flanders and the Netherlands that are likely to be caused by differences in accessibility of secondary care, and possibly existing opioid prescribing habits. Measures to ensure judicious and evidence-based opioid prescribing need to be tailored to the organisation of the healthcare system. [ABSTRACT FROM AUTHOR]

Background: Coping with a chronic disease can be really challenging. Self-management represents a promising strategy to improve daily life experiences. The role of primary healthcare professionals cannot be underestimated in supporting self-management. Due to a shortage of theory, implementation of self-management support is hindered in primary care practice. The aim of this study is to create a conceptual model for self-management support by analysing patients' care experiences towards self-management support. Methods: An explorative-descriptive qualitative study was conducted in Flanders, Belgium. Semi-structured interviews were performed with 16 patients and their informal caregiver (dyads) using a purposive sampling strategy and processed by an inductive content analysis, according to Graneheim and Lundman. Results: Interviews revealed in-depth insights into patients' care experiences. A conceptual model was developed for primary care practice, including five fundamental tasks for healthcare professionals - Supporting, Involving, Listening, Coordinating and Questioning (SILCQ) – contributing to the support of self-management of chronic patients. Conclusions: This qualitative paper emphasises the use of the SILCQ-model to develop optimal roadmaps and hands-on toolkits for healthcare professionals to support self-management. The model needs to be further explored by all stakeholders to support the development of self-management interventions in primary care practice. [ABSTRACT FROM AUTHOR]

Background: In the European Union it is mandatory to include paper package leaflets (PPL) with all medicines, including vaccines, to inform the recipient. However, it is difficult to meet the necessity for localized PPLs in each of the 24 official European languages. Replacing PPLs with electronic versions offers many advantages including redistribution across nations, reduced storage space, accessibility by the visually impaired, easily updated information or the addition of video content. We wanted to assess the attitudes of patients (vaccine recipients or their parents) to the potential of replacing PPL with electronic versions.Methods: We surveyed vaccinees or their parents in four European countries-Belgium, Italy, Bulgaria and France-for their actual use of vaccine PPLs and their opinions about switching to an electronic package leaflet. Our survey was conducted online because of the COVID-19 pandemic and resulted in 2518 responses to a questionnaire targeted at three specific groups with particular information needs: parents of young children, pregnant women and the elderly (≥ 60 years).Results: Our main findings are that currently vaccine PPLs are rarely used and frequently unavailable for the vaccinee. Across the four countries surveyed 55-82% of vaccinees would accept an electronic version, as did 64% when there was an option to request a printout of the leaflet.Conclusions: We found that switching to electronic versions of vaccine PPLs is an acceptable alternative for the public, potentially increasing the quality and amount of information reaching vaccinees while eliminating some barriers to redistribution of vaccines between countries. [ABSTRACT FROM AUTHOR]

BACKGROUND The Asian lady beetle Harmonia axyridis is an important predator of several agricultural pests, including aphids and whiteflies, and thus can contribute to pest management. Commercial viability as a pest control method requires that the beetle can be mass‐reared, and that workable conditions for extended shelf‐life can be guaranteed. One of the features of Harmonia's life cycle is that it enters diapause in the adult stage when the length of the photophase starts shortening in late summer. Reduction of juvenile hormone (JH) titer has been demonstrated to be the common endocrine mechanism inducing reproductive diapause in insects. However, whether H. axyridis enters diapause dependent on JH shutdown and how the JH level is regulated before diapause remains unknown. RESULTS: Like in other insects, the absence of JH triggers the induction and maintenance of reproductive diapause in H. axyridis, indicated by JH measurements and the knockdown of an intracellular JH receptor methoprene‐tolerant (Met). Methoprene, a JH analog, significantly reversed diapause into reproduction via Met. Combined with RNA‐sequencing and RNA interference, we also demonstrated that JH biosynthesis rather than the JH degradation pathway determines the reduction of JH titer in diapausing females. CONCLUSION: Our results reveal the vital role of JH in regulating reproductive diapause in female H. axyridis. Harmonia axyridis diapause could thus be manipulated by targeting JH production and JH signaling. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Recent years have witnessed a steady increase in the number of studies investigating the role of reward prediction errors (RPEs) in declarative learning. Specifically, in several experimental paradigms, RPEs drive declarative learning, with larger and more positive RPEs enhancing declarative learning. However, it is unknown whether this RPE must derive from the participant's own response, or whether instead, any RPE is sufficient to obtain the learning effect. To test this, we generated RPEs in the same experimental paradigm where we combined an agency and a nonagency condition. We observed no interaction between RPE and agency, suggesting that any RPE (irrespective of its source) can drive declarative learning. This result holds implications for declarative learning theory. [ABSTRACT FROM AUTHOR]

Trypsin is a serine protease that is synthesized by the gut epithelial cells of female mosquitoes; it is the enzyme that digests the blood meal. To study its molecular regulation, Culex quinquefasciatus late trypsin was purified by diethylaminoethyl (DEAE), affinity, and C18 reverse-phase high performance liquid chromatography (HPLC) steps, and the N-terminal amino acid sequence was determined for molecular cloning. Five overlapping segments of the late trypsin cDNA were amplified by PCR, cloned, and the full sequence (855 bp) was characterized. Three-dimensional models of the pro-trypsin and activated trypsin were built and compared with other trypsin models. Trypsin modulating oostatic factor (TMOF) concentrations in the hemolymph were determined by ELISA and compared with trypsin activity in the gut after the blood meal. The results showed that there was an increase in TMOF concentrations circulating in the hemolymph which has correlated to the reduction of trypsin activity in the mosquito gut. Northern blot analysis of the trypsin transcripts after the blood meal indicated that trypsin activity also followed the increase and decrease of the trypsin transcript. Injections of different amounts of TMOF (0.025 to 50 μg) decreased the amounts of trypsin in the gut. However, Northern blot analysis showed that TMOF injections did not cause a decrease in trypsin transcript abundance, indicating that TMOF probably affected trypsin translation. [ABSTRACT FROM AUTHOR]

Prescribing patterns by primary care physicians concerning ophthalmic problems were studied using the iCAREdata, a database containing information from the out-of-hours care setting in the Flanders region of Belgium. A very high percentage of prescribed ophthalmic medication was topical antibiotics (89.4%) with tobramycin as the most prevalent substance and in clear conflict with the prevailing guidelines. In addition, a very substantial fraction of prescribed medication contained corticosteroids (30.4%). This is a potentially unsafe option within the technical infrastructure of this setting, which limits the diagnostic possibilities concerning viral infections or preexisting glaucoma risk. We conclude that more efforts are required to limit unnecessary and inappropriate prescribing behavior to further promote patient safety. [ABSTRACT FROM AUTHOR]

Objective Examining the implementation barriers and facilitators of this service as provided by Belgian community pharmacists in collaboration with general practitioners. Setting Community pharmacies in Flanders. Method Qualitative study through interviews of pharmacists and general practitioners. Main outcome measure Opinions and experiences of pharmacists and general practitioners about type 3 medication review. Results Sixteen community pharmacists and thirteen general practitioners were interviewed and generally gave a positive assessment of the project. The general practitioners saw the pharmaceutical and pharmacotherapeutic recommendations of the pharmacists as an added value for the patients. The pharmacists indicated that performing an medication review was time-consuming, but that it improved their professional relationship with general practitioners and patients. They reported obstacles in obtaining information: cumbersome access to individual patient data (laboratory values) and difficulties in finding and choosing adequate medical information sources. Moreover, pharmacists indicated that there is a need for adequate reimbursement and additional training to make the implementation sustainable. Conclusion Both pharmacists and general practitioners were enthusiastic about medication reviews. The implementation improved the interprofessional collaboration. However, important barriers remain, such as the considerable investment of time and the difficulty in gathering all the necessary information. The sustainable implementation of type 3 medication review in Belgium requires adequate reimbursement and additional training. [ABSTRACT FROM AUTHOR]

A key theme in the science education literature concerns the reluctance of students to participate in Science, Technology, Engineering, and Mathematics (STEM). Self-determination theory (SDT) states that social factors in an educational setting, such as teachers' motivating style, can influence students' motivation and engagement. This paper investigates the relationship between STEM teachers' motivating style (autonomy support, provision of structure, involvement) and students' motivation and engagement with regard to STEM. Furthermore, the relationship between students' motivation and students' engagement is investigated. Thirty classroom observations were conducted in different STEM lessons, to assess teachers' motivating style and students' engagement. The students' motivation was assessed at the end of the school year, using an online questionnaire. The results reveal that STEM teachers' provision of structure is positively linked to students' motivation and engagement with regard to STEM subjects. The impact of teachers' autonomy support was negatively predictive for students' autonomous motivation, and positively predictive for students' engagement. A negative relationship between students' controlled motivation and engagement was found. Based on these results, this study suggests that taking teachers' motivating style into account in future educational initiatives regarding STEM is highly relevant as a means of stimulating students' motivation and engagement. [ABSTRACT FROM AUTHOR]

Loss of the insulin-stimulated glucose uptake in muscle is a crucial event participating in the defect of whole-body metabolism in type 2 diabetes. Therefore, identification by Pavarotti et al. (Biochem. J (2021) 478 (2): 407-422) of complexin-2 as an important contributor to glucose transporter 4 (GLUT4) translocation to muscle cell plasma membrane upon insulin stimulation is essential. The present commentary discusses the biological importance of the findings and proposes future challenges and opportunities. [ABSTRACT FROM AUTHOR]

Recent behavioral evidence implicates reward prediction errors (RPEs) as a key factor in the acquisition of episodic memory. Yet, important neural predictions related to the role of RPEs in episodic memory acquisition remain to be tested. Humans (both sexes) performed a novel variable-choice task where we experimentally manipulated RPEs and found support for key neural predictions with fMRI. Our results show that in line with previous behavioral observations, episodic memory accuracy increases with the magnitude of signed (i.e., better/worse-than-expected) RPEs (SRPEs). Neurally, we observe that SRPEs are encoded in the ventral striatum (VS). Crucially, we demonstrate through mediation analysis that activation in the VS mediates the experimental manipulation of SRPEs on episodic memory accuracy. In particular, SRPE-based responses in the VS (during learning) predict the strength of subsequent episodic memory (during recollection). Furthermore, functional connectivity between task-relevant processing areas (i.e., face-selective areas) and hippocampus and ventral striatum increased as a function of RPE value (during learning), suggesting a central role of these areas in episodic memory formation. Our results consolidate reinforcement learning theory and striatal RPEs as key factors subtending the formation of episodic memory. [ABSTRACT FROM AUTHOR]

In recent years, several hierarchical extensions of well-known learning algorithms have been proposed. For example, when stimulus-action mappings vary across time or context, the brain may learn two or more stimulus-action mappings in separate modules, and additionally (at a hierarchically higher level) learn to appropriately switch between those modules. However, how the brain mechanistically coordinates neural communication to implement such hierarchical learning remains unknown. Therefore, the current study tests a recent computational model that proposed how midfrontal theta oscillations implement such hierarchical learning via the principle of binding by synchrony (Sync model). More specifically, the Sync model uses bursts at theta frequency to flexibly bind appropriate task modules by synchrony. The 64-channel EEG signal was recorded while 27 human subjects (female: 21, male: 6) performed a probabilistic reversal learning task. In line with the Sync model, postfeedback theta power showed a linear relationship with negative prediction errors, but not with positive prediction errors. This relationship was especially pronounced for subjects with better behavioral fit (measured via Akaike information criterion) of the Sync model. Also consistent with Sync model simulations, theta phase-coupling between midfrontal electrodes and temporoparietal electrodes was stronger after negative feedback. Our data suggest that the brain uses theta power and synchronization for flexibly switching between task rule modules, as is useful, for example, when multiple stimulusaction mappings must be retained and used. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that reward prediction errors (RPEs) play an important role in declarative learning, but its neurophysiological mechanism remains unclear. Here, we tested the hypothesis that RPEs modulate declarative learning via theta-frequency oscillations, which have been related to memory encoding in prior work. For that purpose, we examined the interaction between RPE and transcranial Alternating Current Stimulation (tACS) in declarative learning. Using a between-subject (real versus sham stimulation group), single-blind stimulation design, 76 participants learned 60 Dutch-Swahili word pairs, while theta-frequency (6 Hz) tACS was administered over the medial frontal cortex (MFC). Previous studies have implicated MFC in memory encoding. We replicated our previous finding of signed RPEs (SRPEs) boosting declarative learning; with larger and more positive RPEs enhancing memory performance. However, tACS failed to modulate the SRPE effect in declarative learning and did not affect memory performance. Bayesian statistics supported evidence for an absence of effect. Our study confirms a role of RPE in declarative learning, but also calls for standardized procedures in transcranial electrical stimulation. [ABSTRACT FROM AUTHOR]

The extensive literature dealing with the Golgi system emphasizes its role in protein secretion and modification, usually without specifying from which evolutionary ancient cell physiological necessity such secretion originated. Neither does it specify which functional requirements the secreted proteins must meet. From a reinterpretation of some classical and recent data gained mainly, but not exclusively, from (insect) endocrinology, the view emerged that the likely primordial function of the rough endoplasmic reticulum (RER)–Golgi complex in all eukaryotes was not the secretion of any type of protein but the removal of toxic excess Ca2+ from the cytoplasm. Such activity requires the concurrent secretion of large amounts of Ca2+-carrying/transporting proteins acting as a micro-conveyor belt system inside the RER–Golgi. Thus, (fitness increasing) protein secretion is subordinate to Ca2+ removal. Milk with its high content of protein and Ca2+ (60–90 mM vs. 100 nM in unstimulated mammary gland cells) is an extreme example. The sarco(endo)plasmatic reticulum Ca2+-ATPases (SERCAs) and SPCA1a Ca2+/Mn2+ transport ATPases are major players in Ca2+ removal through the Golgi. Both are blocked by the sesquiterpenoid thapsigargin. This strengthens the hypothesis (2014) that endogenous farnesol-like sesquiterpenoids (FLSs) may act as the long sought for but still unidentified agonist (s) for Ca2+-pumps in both the ER and Golgi. A second putative function also emerges. The fusion of both the incoming and outgoing transport vesicles, respectively, at the cis - and trans - side of Golgi stacks, with the membrane system requiring high flexibility and fast self-closing of the involved membranes. These properties may—possibly partially—be controlled by endogenous hydrophobic membrane "fluidizers" for which FLSs are prime candidates. A recent reexamination of unexplained classical data suggests that they are likely synthesized by the Golgi itself. This game-changing hypothesis is endorsed by several arguments and data, some of which date from 1964, that the insect corpus allatum (CA), which is the major production site of farnesol-esters, has active Golgi systems. Thus, in addition to secreting FLS, in particular juvenile hormone(s), it also secretes a protein(s) or peptide(s) with thus far unknown function. This paper suggests answers to various open questions in cell physiology and general endocrinology. [ABSTRACT FROM AUTHOR]

Juvenile hormones (JHs) are a group of acyclic sesquiterpenoids. They are biosynthesized in the mevalonate biosynthetic pathway as esters of farnesol (F). F is best known as an intermediate in this pathway that is omnipresent in all eukaryotes. Since 2019 it became apparent that F also has an important role on its own, namely in Ca2+- homeostasis, as a receptor of some types of Ca2+-channels in mammals. JHs occur in 6 forms, they are poorly soluble in water, and they regulate many aspects of insect physiology. In 1967, when the chemical structure of the first insect JH (JH I) was published, the corpora allata (CA), which are located in the head, were assumed to be the only site, or source, of JH-synthesis. However, the fact that JH I had not been extracted from active CA but from abdomens of young (maximum 96 hours old) adult male, not female, Cecropia moths, Hyalophora cecropia, with intact CA presented a problem. Given the large amounts of JH present in the extract, which was called "golden oil", this JH had apparently started to accumulate during metamorphosis. How did JH I end up in the abdomen, why was it quantitatively sex- and tissue-specific, and what was its function(s) and mode of action? First, in 1976 it turned out, unexpectedly, that not the fat body as initially presumed, but the accessory sex glands (MAGs) acted as the exclusive repository for the huge amounts of JHs, namely 2.1 μg JH I and 0.3 μg JH II. It was then thought that the JHs had been synthesized by the CA, although presumed to be inactive during metamorphosis. After a long period with moderate progress, in 2014, it became established MAG-JHs are not synthesized in the CA, but by the MAGs themselves, that they not released into the hemolymph, but secreted, along with other MAG secretions, into the genital duct system of the female during copulation. MAG-JH was named "exocrine JH", to functionally distinguish it from "endocrine/hormonal JH" that is chemically identical but synthesized by the CA in young larvae and adults. Furthermore, the focus on how JH exert its functions also shifted considerably in the past decade, namely towards molecular genetic approaches, in particular to its nuclear- and membrane receptors. Concurrently, the importance of Ca2+- homeostasis and of the hydrophobic properties of JH also got more attention. In the pioneering days of insect endocrinology, JH had become known as the "master-" and as the "status quo hormone", denominations that continue to be used in some textbooks to date. What did status quo originally mean, and how did its meaning gradually evolve towards one of today's interpretations that says that "keeping the cytoplasmic free Ca2+ concentration below the toxicity limit of Ca2+ (when rising above 100 nanomolar) for a longer period of time" is a, if not the key issue. Indeed, without such very low free Ca2+ in the cytoplasm, the well documented secondary signaling systems such as "Ca2+ as a secondary messenger", "Ca2+-induced Ca2+-release from intracellular storage sites (e.g., the endoplasmic reticulum)", and "Control of the activity of some enzyme systems which are anchored in endomembranes, and which can be inhibited by a high intraluminal Ca2+ concentration" could not become functional. Maintaining such low free cytoplasmic concentration of Ca2+ in resting cells is indeed a big challenge because the average Ca2+ concentration, in aqueous extracellular environments, is thousands of times higher (about 2 millimolar or higher). After optimal conditions for maintaining low Ca2+-conditions can be realized, a second level of activity for JHs can start. It is mediated through intranuclear targets/receptors. In our model, extranuclear (membrane-) and nuclear targets/receptors (e.g., transcription factors) are necessarily complementary. [ABSTRACT FROM AUTHOR]

Our rapidly changing society needs highly-qualified STEM professionals (experts in science, technology, engineering, and mathematics) to develop solutions to the problems it is facing. Many of the students who graduate from a STEM programme in secondary education, however, opt out of STEM when enrolling in higher education, often due to a loss of interest. To ensure sufficiently high and qualified enrolment in higher STEM education, we need to bridge this gap between secondary and higher STEM education by showing our youngsters the relevance of science and technology to their personal life and environment. To this end, the project STEM@school promoted and studied the idea of integrated STEM in secondary education in Flanders, Belgium. In integrated STEM education, learning contents from the separate STEM courses are linked in an authentic way, as they often are in our environmental challenges. This approach encourages students as well as their teachers to acquire a robust understanding of STEM concepts, and a creative, inquisitive, and collaborative mindset. For the design of integrated STEM curricula, STEM@school united secondary-school STEM teachers and university researchers. This article elaborates on the principles, opportunities and challenges of the design and implementation of these curricula and discusses their promising effects on students' conceptual understanding and attitudes towards STEM subjects. The article concludes with tips and tricks to get started with integrated STEM education in secondary schools. [ABSTRACT FROM AUTHOR]

Farnesol, the sesquiterpenoid precursor of the six presently known insect juvenile hormones (JHs) was for the first time chemically identified in 1961, not in JH synthesizing glands or whole body extracts, but in excrements of the mealworm Tenebrio molitor. This finding was thought to be irrelevant and remained unexplored. In 1970, it was reported that the fall to zero of the JH titer in both prediapausing adults and in last instar larvae of the Colorado potato beetle causes severe malfunctioning of the Golgi system in the fat body, among various other effects. This endomembrane system in the cytoplasm resides at the intersection of the secretory, lysosomal, and endocytic pathways and is required for the processing of secretory proteins. Why the Golgi needs farnesol-like endogenous sesquiterpenoids (FLS) for its proper functioning has also never been further investigated. In 1999, farnesol was found to be a natural endogenous ligand for particular types of voltage-gated Ca2+ channels in mammalian cells, a finding that also remained undervalued. Only since 2014 more attention has been paid to the functional research of the "noble unknown" farnesol, in particular to its Ca2+-homeostasis-related juvenilizing and anti-apoptotic activities. Here, we introduce the term "Golgicrine activity" that addresses the secretory activity of the RER-Golgi system from its role in Ca2+-homeostasis rather than from its conventional role in mere protein secretion. Golgicrine activity attributes the so far forgotten role of farnesol-like sesquiterpenoids in proper Golgi functioning, and unites the endocrine, exocrine and enterocrine functions of these sesquiterpenoids. This out of the box view may open novel perspectives for the better understanding of particular inflammatory bowel diseases and of neurodegenerative diseases as well, because the early initiation of Alzheimer's disease may possibly result from malfunctioning of the mevalonate-farnesol-cholesterol biosynthetic pathway and thus might be a farnesol- and Ca2+-homeostasis-dependent Golgicrine issue. [ABSTRACT FROM AUTHOR]

In this paper, we explore how students' engagement varies in different STEM (Science, Technology, Engineering, Mathematics) learning environments. More specifically, we focus on the significance of a learning environment applying an integrated STEM (iSTEM) approach and the significance of STEM learning environments' student-centredness. Moreover, we explore the relative importance of different student-centred principles (lesson plan and implementation, communicative interactions, student-teacher relationships) for students' engagement in the STEM learning environment. Applying a mixed-method approach, we draw from observational data of 24 STEM lessons in combination with data from seven focus groups with 67 grade 9 students. The quantitative findings, based on the observational data, show that a learning environment applying an iSTEM approach seems to support students' engagement. Further investigation made it clear that the student-centredness in this learning environment is especially significant. Regarding the specific student-centred principles, all principles had a significant impact on students' engagement. The focus group data make clear that, besides student-centredness, the integrative aspect and the use of authentic real-world problems in iSTEM can also be engaging for students. These results indicate that iSTEM is a good practice to engage students in the STEM learning environment, as it facilitates teachers' implementation of a general student-centred approach. [ABSTRACT FROM AUTHOR]

Thirty years after the first description and modeling of G protein coupled receptors (GPCRs), information about their mode of action is still limited. One of the questions that is hard to answer is: how do the allosteric changes in the GPCR induced by, e.g., ligand binding in the end activate a G protein-dependent intracellular pathway (e.g., via the cAMP or the phosphatidylinositol signal pathways). Another question relates to the role of prenylation of G proteins. Today's "consensus model" states that protein prenylation is required for the assembly of GPCR-G protein complexes. Although it is well-known that protein prenylation is the covalent addition of a farnesyl- or geranylgeranyl moiety to the C terminus of specific proteins, e.g., α or γ G protein, the reason for this strong covalent binding remains enigmatic. The arguments for a fundamental role for prenylation of G proteins other than just being a hydrophobic linker, are gradually accumulating. We uncovered a dilemma that at first glance may be considered physiologically irrelevant, however, it may cause a true change in paradigm. The consensus model suggests that the only functional role of prenylation is to link the G protein to the receptor. Does the isoprenoid nature of the prenyl group and its exact site of attachment somehow matter? Or, are there valid arguments favoring the alternative possibility that a key role of the G protein is to guide the covalently attached prenyl group to – and it hold it in – a very specific location in between specific helices of the receptor? Our model says that the farnesyl/prenyl group – aided by its covalent attachment to a G protein -might function in GPCRs as a horseshoe-shaped flexible (and perhaps flip-flopping) hydrophobic valve for restricting (though not fully inhibiting) the untimely passage of Ca2+, like retinal does for the passage of H+ in microbial rhodopsins that are ancestral to many GPCRs. [ABSTRACT FROM AUTHOR]

Changes in titers of Juvenile Hormone(s) [JH(s)], the "status quo" hormone, and the molting hormone 20-OH-Ecdysone (20E), since 2019 also referred to as the anabolic steroid of plant origin named Vitamin D1, are key players in insect metamorphosis. Ecdysterone 20E is a water- and lipid soluble compound. Juvenile hormone (JH) occurs in six sesquiterpenoids isoforms, which are esters of farnesol, all highly hydrophobic compounds with high affinity for cell membranes. They are synthesized by the mevalonate biosynthetic pathway found in uniand multicellular eukaryotes, including the evolutionarily ancient zooflagellates (Opisthokonta), which are presumed as ancestral to all animals. The mevalonate pathway of insects does not include the enzyme squalene synthase. Hence, they cannot biosynthesize cholesterol, the precursor for the biosynthesis of (ecdy)steroid hormones. Cholesterol and plant steroids are utilized as vitamins by insects. What is the mechanism that drastically reduces the titer of JH causing metamorphosis in holometabolous insects? How can the absence of JH cause drastic changes in insect development? Could this be caused by the collapse of Ca-homeostasis after the binding sites for endogenous sesquiterpenoids on Ca channels, Ca2+ pumps, etc. are no longer occupied? What is the exact mode of action of 20E/vitamin D1, not only in insects but also in humans? Are JH and 20E antagonists, as was already postulated during the 1960s? Do both hormones compete for the same receptors? We argue that this is not the case and offer an alternative explanation. First, not only the nuclear, but also the membrane receptors of JH and 20E differ. Second, both hormones seem to antagonistically control Ca2+-homeostasis of target cells. Farnesol, an agonist of JH-biosynthesis, is a potent inhibitor of specific voltage-gated Ca2+- channels, and thus inhibits the influx of Ca2+ in target cells. In contrast, upon activation of its membrane GPCR, 20E facilitates the influx of Ca2+ into the cytoplasm. In essence, hormonepropelled changes in intracellular free Ca2+-concentration, [Ca2+]i, are the primordial driving force of complete metamorphosis. This hypothesis explains genomic and non-genomic effects that occur at high or low hormonal titers. [ABSTRACT FROM AUTHOR]

Objective: The accessibility of contraceptives varies greatly from country to country. Because unintended pregnancies have a considerable impact, programmes have been initiated in some countries to make certain contraceptives available without a prescription. We therefore investigated whether or not Flanders, the Dutch-speaking part of Belgium, is ready for such an initiative.Method: We used a mixed-methods approach with a mainly qualitative methodology. The opinions of pharmacists, general practitioners (GPs) and gynaecologists, the three types of health care provider most closely involved in the prescription and delivery of contraception, were examined.Results: A majority of pharmacists supported the idea. Moreover, a large majority occasionally dispensed hormonal contraception without a prescription. Pharmacists expected negative responses from physicians. Among GPs and gynaecologists, a small majority supported the idea conditionally. A minority either fully supported the idea or found it completely unacceptable.Conclusion: Economic aspects were clearly important in forming an opinion on the topic, although medical arguments were often used when they happened to point in the same direction. Flemish pharmacists were willing to train for and implement a new service that would provide contraceptives without a prescription. The majority of GPs and gynaecologists expressed reservations about such a service and doubted that it would reduce unintended pregnancies. If this service were to be implemented, caution would be needed to avoid giving contraceptive users conflicting information. [ABSTRACT FROM AUTHOR]

Farnesol, the sesquiterpenoid precursor of insect juvenile hormones (JH) that itself has JH activity, existed already long before animals and their hormones came into being. Although it is omnipresent in all eukaryotes, this molecule remains a "noble unknown" in cell physiology. It is neither documented as a hormone nor as another type of signaling molecule. To date, its function as an intermediate in the synthesis of squalene-cholesterol-steroids in chordates/vertebrates, and of the insect/arthropod JHs, esters of farnesol, in the mevalonate biosynthetic pathway is assumed to be the only one. This assumption neglects that already two decades ago, farnesol has been shown to be a potent endogenous inhibitor of N-type voltage-gated Ca2+ channels in some mammalian cell types. The tandem mevalonate pathway and Ca2+ channels originated early in eukaryotic evolution, and has since been well conserved, "promoting" it as a ubiquitous player in Ca2+ homeostasis in all eukaryotes. This paper accentuates how this drastic change in thinking gained momentum after the discovery by Paroulek and Sláma that the huge amounts of JH I in male accessory glands of the Cecropia moth, are actually synthesized in these glands themselves and not in the corpora allata, the hitherto assumed unique synthesis site of such compounds. In addition, MAG-JHs have no hormonal- but an exocrine function. Here we hypothesize that MAG-JHs may function in protecting the spermatozoa against toxic Ca2+ concentrations, and in enabling their flagellum to undulate. They may do so by acting through membrane receptors. Our novel paradigm assigns to farnesol/JHs a function of flexible hydrophobic molecular valves for restricting untimely Ca2+-passage through some types of canonical Ca2+channels, using covalently bound farnesyl- or geranyl-geranyl group attachment as well as GPCRs-G proteins all containing a prenyl group. The high rotatable bond count, and their horseshoe-shape are instrumental to their valve function. In our paradigm, Met/Tai and Gce, to date generally thought to be the (only) functional (nuclear) receptors for JHs, are classified as probable Ca2+-sensitive transcription factors. Some theoretical and practical considerations for possible applications in a medical context will be discussed. [ABSTRACT FROM AUTHOR]

After many years of sometimes heated discussions, the problem regarding the relative importance of two classical dogmas of the Nature (genes and sex-steroid hormones) versus Nurture (education, teaching-learning etc.) debate, is still awaiting a conclusive solution. Males and females differ in only a few (primordial) genes as is well documented by genomic analyses. However, their sexand gender-specific behavior and physiology is nevertheless profoundly different, even if they grew up in a similar (educational) environment. By extending the "Calcigender-concept", originally formulated in 2015, to the simplistic binary Nature versus Nurture concept, a novel framework showing that the sex-steroid hormone-dependent intracellular Calcium concentration is an important third factor may emerge. Although the principles of animal physiology and evolution strongly stress the fact that Nature is always dominant, Nurture can, to a limited extent, play a mitigating role. [ABSTRACT FROM AUTHOR]

Abstract: Background: Seborrheic keratosis (SK) of the outer ear canal is rarely described in literature. Etiological risk factors involved in SK such as exposure to human papillomavirus (HPV) and ultraviolet (UV) light are established but must still be confirmed. In recent years, new insights into the pathogenesis of SKs occurred in the area of molecular pathogenesis. Fibroblast growth factor receptor 3 (FGFR3) gene and p110α subunit of phosphoinositide 3‐kinase (PIK3CA) oncogene mutations are known to be involved. Methods: We describe two cases of SK of the outer ear canal. We conducted a review of literature and examined the role of etiological risk factors involved in our cases. The lesions were primarily treated with surgical resection. Postoperatively, in both patients, the lesions recurred after a considerably long disease‐free interval. We tested both FGFR3 and PIK3CA genes for mutations, in the primary and recurrent lesions. Results: We did not find any mutations in both genes in all samples. Conclusion: Additional research is needed to further establish possible etiological risk factors and to clarify the involvement of PIK3CA and FGFR3 genes in the pathogenesis of seborrheic keratosis of the outer ear canal. These cases underscore the need for meticulous diagnosis, treatment, and sufficient long‐term follow‐up. [ABSTRACT FROM AUTHOR]

Recent associative models of cognitive control hypothesize that cognitive control can be learned (optimized) for task-specific settings via associations between perceptual, motor, and control representations, and, once learned, control can be implemented rapidly. Midfrontal brain areas signal the need for control, and control is subsequently implemented by biasing sensory representations, boosting or suppressing activity in brain areas processing task-relevant or task-irrelevant information. To assess the timescale of this process, we employed EEG. In order to pinpoint control implementation in specific sensory areas, we used a flanker task with incongruent flankers shown in only one hemifield (congruent flankers in the other hemifield) isolating their processing in the contralateral hemisphere. ERPs revealed fast modulations specifically in visual processing areas contralateral to the incongruent flankers. To test whether these modulations reflect increased or decreased processing of incongruent flankers, we investigated alpha power, a marker for attentional inhibition. Importantly, we show increased alpha power over visual areas processing incongruent flankers from 300 to 500 ms poststimulus onset. This suggests fast cognitive control by attentional inhibition for information disrupting goal-oriented actions. Additionally, we show that midfrontal theta earlier in the trial is also modulated by incongruency, and that theta power predicts subsequent alpha power modulations. This supports the hypothesis that midfrontal incongruency detection leads to control implementation, and reveals that these mechanisms take place on a fast, within-trial timescale. [ABSTRACT FROM AUTHOR]

Reward prediction errors (RPEs) are thought to drive learning. This has been established in procedural learning (e.g., classical and operant conditioning). However, empirical evidence on whether RPEs drive declarative learning–a quintessentially human form of learning–remains surprisingly absent. We therefore coupled RPEs to the acquisition of Dutch-Swahili word pairs in a declarative learning paradigm. Signed RPEs (SRPEs; “better-than-expected” signals) during declarative learning improved recognition in a follow-up test, with increasingly positive RPEs leading to better recognition. In addition, classic declarative memory mechanisms such as time-on-task failed to explain recognition performance. The beneficial effect of SRPEs on recognition was subsequently affirmed in a replication study with visual stimuli. [ABSTRACT FROM AUTHOR]

Neuropeptides are by far the largest and most diverse group of signaling molecules in multicellular organisms. They are ancient molecules important in regulating a multitude of processes. Their small proteinaceous character allowed them to evolve and radiate quickly into numerous different molecules. On average, hundreds of distinct neuropeptides are present in animals, sometimes with unique classes that do not occur in distantly related species. Acting as neurotransmitters, neuromodulators, hormones, or growth factors, they are extremely diverse and are involved in controlling growth, development, ecdysis, digestion, diuresis, and many more physiological processes. Neuropeptides are also crucial in regulating myriad behavioral actions associated with feeding, courtship, sleep, learning and memory, stress, addiction, and social interactions. In general, behavior ensures that an organism can survive in its environment and is defined as any action that can change an organism's relationship to its surroundings. Even though the mode of action of neuropeptides in insects has been vigorously studied, relatively little is known about most neuropeptides and only a few model insects have been investigated. Here, we provide an overview of the roles neuropeptides play in insect behavior. We conclude that multiple neuropeptides need to work in concert to coordinate certain behaviors. Additionally, most neuropeptides studied to date have more than a single function. [ABSTRACT FROM AUTHOR]

In the classical "mind-body" wording, "body" is usually associated with the "mass aspect" of living entities and "mind" with the "immaterial" one. Thoughts, consciousness and soul are classified as immaterial. A most challenging question emerges: Can something that is truly immaterial, thus that in the wording of physics has no mass, exist at all? Many will answer: "No, impossible." My answer is that it is very well possible, that no esoteric mechanisms need to be invoked, but that this possibility is inherent to 2 well established but undervalued physiological mechanisms. The first one is electrical in nature. In analogy with "genome," "proteome" etc. "electrome" (a novel term) stands for the totality of all ionic currents of any living entity, from the cellular to the organismal level. Cellular electricity is truly vital. Death of any cell ensues at the very moment that it irreversibly (excluding regeneration) loses its ability to realize its electrical dimension. The second mechanism involves communication activity that is invariably executed by sender-receiver entities that incessantly handle information. Information itself is immaterial (D no mass). Both mechanisms are instrumental to the functioning of all cells, in particular to their still enigmatic cognitive memory system. Ionic/electrical currents associated with the cytoskeleton likely play a key role but have been largely overlooked. This paper aims at initiating a discussion platform from which students with different backgrounds but all interested in the immaterial dimension of life could engage in elaborating an integrating vocabulary and in initiating experimental approaches. [ABSTRACT FROM AUTHOR]

Intractable aspiration is a serious, often life-threatening condition due to its potential impact on pulmonary function. Aspiration requires therapeutic measures, starting with conservative management but often necessitating surgical treatment. The basic surgical principle is to separate the alimentary and respiratory tracts through a variety of procedures which, unfortunately, nearly all result in the loss of phonation, with the exception of total laryngectomy (TL) which includes the placement of an indwelling voice prosthesis. In this study, we present a modified laryngotracheal separation (LTS) technique that, we believe, offers multiple advantages compared to standard TL. After reviewing the medical records of 35 patients with intractable aspiration who have undergone LTS, we describe the surgical technique and present the postoperative result. In a second surgical procedure about two months following LTS, we aimed to achieve voice restoration by placement of an indwelling voice prosthesis. Intractable aspiration was successfully treated in all patients. Placement of an indwelling voice prosthesis during a second operation was successful in 15 patients, representing the largest reported cohort thus far. LTS is a reliable surgical technique to treat intractable aspiration, with restoration of oral intake, thereby improving the general condition and quality of life of these unfortunate patients. Furthermore, voice restoration can be achieved in selected patients, by placement of a voice prosthesis. [ABSTRACT FROM AUTHOR]

Consciousness and working memory are two widely studied cognitive phenomena. Although they have been closely tied on a theoretical and neural level, empirical work that investigates their relation is largely lacking. In this study, the relationship between visual consciousness and different working memory components is investigated by using a dual-task paradigm. More specifically, while participants were performing a visual detection task to measure their visual awareness threshold, they had to concurrently perform either an executive or visuospatial working memory task. We hypothesized that visual consciousness would be hindered depending on the type and the size of the load in working memory. Results showed that maintaining visuospatial content in working memory hinders visual awareness, irrespective of the amount of information maintained. By contrast, the detection threshold was progressively affected under increasing executive load. Interestingly, increasing executive load had a generic effect on detection speed, calling into question whether its obstructing effect is specific to the visual awareness threshold. Together, these results indicate that visual consciousness depends differently on executive and visuospatial working memory. [ABSTRACT FROM AUTHOR]

Background: A longstanding debate exists about including a 'reason for use' on prescriptions for medication. Little is known, however, about patients' opinions on this subject.Methods: An internet-based questionnaire, consisting mainly of Likert scale questions, was distributed online to the general public in Belgium. Results from 1034 responses were analyzed using descriptive statistics.Results: Opinions from patients toward including a 'reason for use' on medication prescriptions were generally positive. A clear majority of 62% increased to 74% after providing information about the possible link between indication and medication dose. A majority of the participants expressed a positive attitude regardless of the pathology involved, although sexually transmitted diseases were of greatest concern. Other important aspects differentiating the opinion positively was the transmission of this information in an electronic-only form and limiting it to the regular pharmacist excluding further use by third parties such as other pharmacies or insurance companies. Patients using multiple medicines and those frequenting the same pharmacy also had a more favorable opinion about including the reason for use. In addition, analysis of physician and pharmacist questionnaire responses, explicitly excluded from the main analysis, confirmed the known contrasting opinions in these subgroups.Conclusions: Patients have strong support for transferring information on the 'reason for use' of their prescriptions to their regular pharmacy if this is done in a secure and privacy-conscious way enabling increased patient safety and improved pharmaceutical care. [ABSTRACT FROM AUTHOR]