Non-hyperpolarizing GABA B receptor activation regulates neuronal migration and neurite growth and specification by cAMP/LKB1

γ-Aminobutyric acid is the principal inhibitory neurotransmitter in adults, acting through ionotropic chloride-permeable GABAA receptors (GABAARs), and metabotropic GABABRs coupled to calcium or potassium channels, and cyclic AMP signalling. During early development, γ-aminobutyric acid is the main neurotransmitter and is not hyperpolarizing, as GABAAR activation is depolarizing while GABABRs lack coupling to potassium channels. Despite extensive knowledge on GABAARs as key factors in neuronal development, the role of GABABRs remains unclear. Here we address GABABR function during rat cortical development by in utero knockdown (short interfering RNA) of GABABR in pyramidal-neuron progenitors. GABABR short interfering RNA impairs neuronal migration and axon/dendrite morphological maturation by disrupting cyclic AMP signalling. Furthermore, GABABR activation reduces cyclic AMP-dependent phosphorylation of LKB1, a kinase involved in neuronal polarization, and rescues LKB1 overexpression-induced defects in cortical development. Thus, non-hyperpolarizing activation of GABABRs during development promotes neuronal migration and morphological maturation by cyclic AMP/LKB1 signalling

Analisis Kesadaran Dan Kepatuhan Terhadap Norma Hukum Di Lingkungan Masyarakat Untuk Mencapai Keadilan

This research in-depth investigates the implementation of awareness and compliance with legal norms in the community with the main aim of achieving optimal levels of justice. Through a cross-disciplinary approach, this research details the factors that influence levels of awareness and compliance, while analyzing their impact on efforts to create a more equitable environment. Research methods include the use of surveys and quantitative data analysis, which produces findings highlighting the challenges faced in implementing legal norms. As a result of this research, various obstacles were discovered that need to be overcome in order to strengthen society's compliance with legal norms and, thereby, increase effectiveness in achieving better social justice. The proposed recommendations include concrete steps to overcome these obstacles, paving the way for better understanding and application of legal norms in order to achieve broader justice goals

Home indoor air quality and cognitive function over one year for people working remotely during COVID

The coronavirus disease 2019 (COVID-19) pandemic triggered an increase in remote work-from-home for office workers. Given that many homes now function as offices despite not being designed to support office work, it is critical to research the impact of indoor air quality (IAQ) in homes on the cognitive performance of people working from home. In this study, we followed 206 office workers across the U.S. over one year under remote or hybrid-remote settings during 2021&ndash;2022. Participants placed two real-time, consumer-grade indoor environmental monitors in their home workstation area and bedroom. Using a custom smartphone application geofenced to their residential address, participants responded to surveys and periodic cognitive function tests, including the Stroop color&ndash;word interference test, Arithmetic two-digit addition/subtraction test, and Compound Remote Associates Task (cRAT). Exposures assessed included carbon dioxide (CO2) and thermal conditions (indoor heat index: a combination of temperature and relative humidity) averaged over 30 min prior to each cognitive test. In adjusted longitudinal mixed models (n &le; 126), we found that indoor thermal conditions at home were associated with cognitive function outcomes non-linearly (p &lt; 0.05), with poorer cognitive performance on the Stroop test and poorer creative problem-solving on the cRAT when conditions were either too warm or too cool. Most indoor CO2 levels were &lt;640 ppm, but there was still a slight association between higher CO2 and poorer cognitive performance on Stroop (p = 0.09). Our findings highlight the need to enhance home indoor environmental quality for optimal cognitive function during remote work, with benefits for both employees and employers.</p

Instructional Strategies to Enhance Dermoscopic Image Interpretation Education: a Review of the Literature

Introduction: In image interpretation education, many educators have shifted away from traditional methods that involve passive instruction and fragmented learning to interactive ones that promote active engagement and integrated knowledge. By training pattern recognition skills in an effective manner, these interactive approaches provide a promising direction for dermoscopy education. Objectives: A narrative review of the literature was performed to probe emerging directions in medical image interpretation education that may support dermoscopy education. This article represents the second of a two-part review series. Methods: To promote innovation in dermoscopy education, the International Skin Imaging Collaboration (ISIC) assembled an Education Working Group that comprises international dermoscopy experts and educational scientists. Based on a preliminary literature review and their experiences as educators, the group developed and refined a list of innovative approaches through multiple rounds of discussion and feedback. For each approach, literature searches were performed for relevant articles. Results: Through a consensus-based approach, the group identified a number of theory-based approaches, as discussed in the first part of this series. The group also acknowledged the role of motivation, metacognition, and early failures in optimizing the learning process. Other promising teaching tools included gamification, social media, and perceptual and adaptive learning modules (PALMs). Conclusions: Over the years, many dermoscopy educators may have intuitively adopted these instructional strategies in response to learner feedback, personal observations, and changes in the learning environment. For dermoscopy training, PALMs may be especially valuable in that they provide immediate feedback and adapt the training schedule to the individual’s performance

Theory-Based Approaches to Support Dermoscopic Image Interpretation Education: A Review of the Literature

Introduction: Efficient interpretation of dermoscopic images relies on pattern recognition, and the development of expert-level proficiency typically requires extensive training and years of practice. While traditional methods of transferring knowledge have proven effective, technological advances may significantly improve upon these strategies and better equip dermoscopy learners with the pattern recognition skills required for real-world practice. Objectives: A narrative review of the literature was performed to explore emerging directions in medical image interpretation education that may enhance dermoscopy education. This article represents the first of a two-part review series on this topic. Methods: To promote innovation in dermoscopy education, the International Skin Imaging Collaboration (ISIC)assembled a 12-member Education Working Group that comprises international dermoscopy experts and educational scientists. Based on a preliminary literature review and their experiences as educators, the group developed and refined a list of innovative approaches through multiple rounds of discussion and feedback. For each approach, literature searches were performed for relevant articles. Results: Through a consensus-based approach, the group identified a number of emerging directions in image interpretation education. The following theory-based approaches will be discussed in this first part: whole-task learning, microlearning, perceptual learning, and adaptive learning. Conclusions: Compared to traditional methods, these theory-based approaches may enhance dermoscopy education by making learning more engaging and interactive and reducing the amount of time required to develop expert-level pattern recognition skills. Further exploration is needed to determine how these approaches can be seamlessly and successfully integrated to optimize dermoscopy education

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

FAKTOR-FAKTOR YANG BERHUBUNGAN DENGAN PEMANFAATAN LAYANAN VOLUNTARY COUNSELING AND TESTING (VCT) OLEH KELOMPOK LELAKI SEKS LELAKI (LSL) DI KOTA PADANG TAHUN 2018

ABSTRAK Tujuan Data Kemenkes RI (2016) melaporkan LSL merupakan faktor risiko tertinggi kedua (39%) dalam penularan kasus HIV/AIDS. HIV/AIDS pada LSL terus meningkat dari tahun 2014-2016 (3.858-13.063 kasus HIV). Salah satu program yang dilaksanakan pemerintah untuk mencegah penularan HIV dan AIDS adalah layanan Voluntary Counseling and Testing (VCT). SIHA (2017) melaporkan 6,94% LSL yang melakukan tes HIV dinyatakan positif HIV. Tujuan penelitian ini adalah untuk mengetahui faktor yang berhubungan dengan pemanfaatan layanan VCT oleh kelompok LSL di Kota Padang tahun 2018. Metode Desain penelitian yang digunakan adalah cross sectional. Pengumpulan data dilakukan pada bulan Maret 2019 dengan responden sebanyak 66 responden, yang diambil secara purposive sampling. Pengumpulan data menggunakan kuesioner. Data diuji dengan Data dianalisis secara univariat, bivariat dan multivariat dengan menggunakan uji statistik Chi-Square dan regresi logistik. Hasil Hasil uji statistik menunjukkan terdapat hubungan bermakna antara peran tenaga kesehatan (p=0,001) dan dukungan teman sebaya (p=0,014) terhadap pemanfaatan layanan VCT. Hasil uji multivariat menunjukkan peran tenaga kesehatan merupakan variabel yang paling berpengaruh setelah dikontrol oleh variabel lain (p=0,003). Kesimpulan Peran tenaga kesehatan, dan dukungan teman sebaya memiliki hubungan yang signifikan dengan pemanfaatan layanan VCT. Diharapkan tenaga kesehatan lebih sering melakukan kegiatan yang dapat mempromosikan layanan VCT sehingga dapat menjangkau semua LSL yang ada. Kata Kunci : HIV/AIDS, Konseling dan Tes HIV Sukarela, Lelaki Seks Lelak

Faktor-Faktor Yang Berhubungan Dengan Pemanfaatan Layanan Voluntary Counseling And Testing (VCT) Oleh Kelompok Lelaki Seks Lelaki (LSL) di Kota Padang Tahun 2019

Data Kemenkes RI (2016) melaporkan LSL merupakan faktor risiko tertinggi kedua (39%) dalam penularan kasus HIV/AIDS. HIV/AIDS pada LSL terus meningkat dari tahun 2014-2016 (3.858-13.063 kasus HIV). Salah satu program yang dilaksanakan pemerintah untuk mencegah penularan HIV dan AIDS adalah layanan Voluntary Counseling and Testing (VCT). SIHA (2017) melaporkan 6,94% LSL yang melakukan tes HIV dinyatakan positif HIV. Tujuan penelitian ini adalah untuk mengetahui faktor yang berhubungan dengan pemanfaatan layanan VCT oleh kelompok LSL di Kota Padang tahun 2019. Desain penelitian yang digunakan adalah cross sectional. Pengumpulan data dilakukan pada bulan Maret 2019 dengan responden sebanyak 66 responden, yang diambil secara purposive sampling. Pengumpulan data menggunakan kuesioner. Data dianalisis secara univariat, bivariat dan multivariat dengan menggunakan uji statistik Chi-Square dan regresi logistik. Hasil uji statistik multivariat menunjukkan terdapat hubungan bermakna antara peran tenaga kesehatan dan dukungan teman sebaya dengan pemanfaatan layanan VCT. LSL yang mendapat dukungan dari tenaga kesehatan 5,7 kali lebih berisiko memanfaatkan layanan VCT daripada yang tidak mendapat dukungan. LSL yang mendapat dukungan dari teman sebaya 2,6 kali lebih berisiko memanfaatkan layanan VCT daripada yang tidak mendapat dukungan. Diharapkan tenaga kesehatan lebih sering melakukan kegiatan yang dapat mempromosikan layanan VCT sehingga dapat menjangkau semua LSL dan teman sebayanya. &nbsp

Phosphorylation of E3 Ligase Smurf1 Switches Its Substrate Preference in Support of Axon Development

SummaryUbiquitin E3 ligases serve for ubiquitination of specific substrates, and its ligase efficacy is regulated by interacting proteins or substrate modifications. Whether and how the ligases themselves are modified by cellular signaling is unclear. Here we report that protein kinase A (PKA)-dependent phosphorylation of Smad Ubiquitin Regulatory Factor 1 (Smurf1) can switch its substrate preference between two proteins of opposing actions on axon development. Extracellular factors that promote axon formation elevated Smurf1 phosphorylation at a PKA site Thr306, and preventing this phosphorylation reduced axon formation in cultured hippocampal neurons and impaired polarization of cortical neurons in vivo. Thr306-phosphorylation changed the relative affinities of Smurf1 for its substrates, leading to reduced degradation of polarity protein Par6 and increased degradation of growth-inhibiting RhoA. Thus, PKA-dependent phosphorylation of the E3 ligase could switch its substrate preference, contributing to selective protein degradation required for localized cellular function