Pathogenic and low-frequency variants in children with central precocious puberty

Background: Central precocious puberty (CPP) due to premature activation of GnRH secretion results in early epiphyseal fusion and to a significant compromise in the achieved final adult height. Currently, few genetic determinants of children with CPP have been described. In this translational study, rare sequence variants in MKRN3, DLK1, KISS1, and KISS1R genes were investigated in patients with CPP. Methods: Fifty-four index girls and two index boys with CPP were first tested by Sanger sequencing for the MKRN3 gene. All children found negative (n = 44) for the MKRN3 gene were further investigated by whole exome sequencing (WES). In the latter analysis, the status of variants in genes known to be related with pubertal timing was compared with an in-house Cypriot control cohort (n = 43). The identified rare variants were initially examined by in silico computational algorithms and confirmed by Sanger sequencing. Additionally, a genetic network for the MKRN3 gene, mimicking a holistic regulatory depiction of the crosstalk between MKRN3 and other genes was designed. Results: Three previously described pathogenic MKRN3 variants located in the coding region of the gene were identified in 12 index girls with CPP. The most prevalent pathogenic MKRN3 variant p.Gly312Asp was exclusively found among the Cypriot CPP cohort, indicating a founder effect phenomenon. Seven other CPP girls harbored rare likely pathogenic upstream variants in the MKRN3. Among the 44 CPP patients submitted to WES, nine rare DLK1 variants were identified in 11 girls, two rare KISS1 variants in six girls, and two rare MAGEL2 variants in five girls. Interestingly, the frequent variant rs10407968 (p.Gly8Ter) of the KISS1R gene appeared to be less frequent in the cohort of patients with CPP. Conclusion: The results of the present study confirm the importance of the MKRN3-imprinted gene in genetics of CPP and its key role in pubertal timing. Overall, the results of the present study have emphasized the importance of an approach that aligns genetics and clinical aspects, which is necessary for the management and treatment of CPP

Facing the Realities of Pragmatic Design Choices in Environmental Health Studies: Experiences from the Household Air Pollution Intervention Network Trial

Objective: Household Air Pollution Intervention Network (HAPIN) investigators tested a complex, non-pharmacological intervention in four low- and middle-income countries as a strategy to mitigate household air pollution and improve health outcomes across the lifespan. Intervention households received a liquefied petroleum gas (LPG) stove, continuous fuel delivery and regular behavioral reinforcements for 18 months, whereas controls were asked to continue with usual cooking practices. While HAPIN was designed as an explanatory trial to test the efficacy of the intervention on four primary outcomes, it introduced several pragmatic aspects in its design and conduct that resemble real-life conditions. We surveyed HAPIN investigators and asked them to rank what aspects of the design and conduct they considered were more pragmatic than explanatory. Methods: We used the revised Pragmatic Explanatory Continuum Indicator Summary (PRECIS-2) to survey investigators on the degree of pragmatism in nine domains of trial design and conduct using a five-point Likert rank scale from very explanatory (1) to very pragmatic (5). We invited 103 investigators. Participants were given educational material on PRECIS-2, including presentations, papers and examples that described the use and implementation of PRECIS-2. Results: Thirty-five investigators (mean age 42 years, 51% female) participated in the survey. Overall, only 17% ranked all domains as very explanatory, with an average (±SD) rank of 3.2 ± 1.4 across domains. Fewer than 20% of investigators ranked eligibility, recruitment or setting as very explanatory. In contrast, ≥50% of investigators ranked the trial organization, delivery and adherence of the intervention and follow-up as very/rather explanatory whereas ≤17% ranked them as rather/very pragmatic. Finally, &lt;25% of investigators ranked the relevance of outcomes to participants and analysis as very/rather explanatory whereas ≥50% ranked then as rather/very pragmatic. In-country partners were more likely to rank domains as pragmatic when compared to investigators working in central coordination (average rank 3.2 vs. 2.8, respectively; Wilcoxon rank-sum p &lt; 0.001). Conclusion: HAPIN investigators did not consider their efficacy trial to be rather/very explanatory and reported that some aspects of the design and conduct were executed under real-world conditions; however, they also did not consider the trial to be overly pragmatic. Our analysis underscores the importance of using standardized tools such as PRECIS-2 to guide early discussions among investigators in the design of environmental health trials attempting to measure efficacy.</jats:p

Digital Redesign of Problem-Based Learning (PBL) from Face-to-Face to Synchronous Online in Biomedical Sciences MSc Courses and the Student Perspective

PBL is a widely used teaching approach that is increasingly incorporating digital components. Although, by its nature, a face-to-face approach is the preferred mode of delivery, its digital counterpart is gaining ground. The current paper discusses the digital redesign of PBL in an MSc in Biomedical Sciences. Face-to-face and online PBL followed the seven steps of the PBL process, and each case was completed in three sessions. For the delivery of online PBL, collaborative tools were utilized, including CiscoWebex, the online platform for synchronous meetings, and OneDrive, shareable PPT, and Moodle for synchronous and asynchronous self-directed learning. Three cohorts were followed, and students had both face-to-face and online PBL experiences. Student feedback was obtained using focus groups, and data analysis utilized a deductive and inductive approach. Our data indicate that CiscoWebex is a suitable and user-friendly platform for synchronous online PBL. The students enjoyed both formats and stated that online PBL is an effective teaching approach for promoting student learning. In regards to student interaction, the face-to-face mode was preferred, while online PBL was perceived as more organized. The redesign allowed for effective student learning and could pave the way forward for a fully online MSc program in Biomedical Sciences

Motivación, Desafíos, Apoyo (MDA) Modelo de Ciclo para el Desarrollo de Tutores ABP

Problem-Based Learning (PBL) is well known for enhancing students’ problem-solving skills and teamwork, while the role of PBL tutors is to facilitate discussion rather than teach. This study used four focus groups to explore PBL tutors’ motivation, challenges and support mechanisms, and the relationship between these. The study found that there was a narrative alignment, whereby tutors identified a challenge if it disrupted their motivation to tutor, and support as effective if it addressed the challenge so as to re-establish their motivation. Based on this, we propose the “Motivation, Challenges, Support (MCS) Cycle Model” for the development of PBL tutors.El aprendizaje basado en problemas (ABP) es conocido por mejorar las habilidades de resolución de problemas y el trabajo en equipo de los estudiantes, mientras el papel de los tutores de ABP es facilitar el debate en lugar de enseñar. Este estudio utilizó cuatro grupos focales para explorar la motivación, los desafíos y los mecanismos de apoyo de los tutores de ABP, y la relación entre estos. El estudio encontró que había una alineación narrativa, por la cual los tutores identificaban un desafío si alteraba su motivación de tutor, y el apoyo era efectivo si abordaba el desafío como para restablecer su motivación. En base a esto, proponemos el "Modelo de Ciclo de Motivación, Desafíos, Apoyo (MDA)" para el desarrollo de tutores de ABP

Trust in Authorities and Demographic Factors Affect Vaccine Acceptance during the COVID-19 Pandemic in Cyprus

The COVID-19 pandemic has had a devastating impact on all aspects of human life. Accurately measuring vaccine acceptance and understanding the factors that influence vaccine attitudes and behaviors is crucial to designing public-health interventions to reduce the impact of COVID-19 through vaccinations. The current study adapted the vaccine acceptance scale (Sarathchandra et al., 2018) to the Greek language and assessed the relationship between key components of vaccine acceptance to COVID-19 vaccine beliefs and attitudes, personal and family vaccination history and attitudes, and demographic variables (age, sex, education, and having children). The adapted vaccine acceptance instrument was found to have high internal consistency reliability. Further analyses indicated that younger and less-educated individuals are more vaccine-hesitant, and that vaccine acceptance is influenced by trust in authorities. These findings may have implications for understanding vaccine hesitancy and for the design and implementation of vaccine-related public health policies

Trust in Authorities and Demographic Factors Affect Vaccine Acceptance during the COVID-19 Pandemic in Cyprus

The COVID-19 pandemic has had a devastating impact on all aspects of human life. Accurately measuring vaccine acceptance and understanding the factors that influence vaccine attitudes and behaviors is crucial to designing public-health interventions to reduce the impact of COVID-19 through vaccinations. The current study adapted the vaccine acceptance scale (Sarathchandra et al., 2018) to the Greek language and assessed the relationship between key components of vaccine acceptance to COVID-19 vaccine beliefs and attitudes, personal and family vaccination history and attitudes, and demographic variables (age, sex, education, and having children). The adapted vaccine acceptance instrument was found to have high internal consistency reliability. Further analyses indicated that younger and less-educated individuals are more vaccine-hesitant, and that vaccine acceptance is influenced by trust in authorities. These findings may have implications for understanding vaccine hesitancy and for the design and implementation of vaccine-related public health policies