Autophagy coordinates chondrocyte development and early joint formation in zebrafish

Autophagy is a catabolic process responsible for the removal of waste and damaged cellular components by lysosomal degradation. It plays a key role in fundamental cell processes, including ER stress mitigation, control of cell metabolism, and cell differentiation and proliferation, all of which are essential for cartilage cell (chondrocyte) development and survival, and for the formation of cartilage. Correspondingly, autophagy dysregulation has been implicated in several skeletal disorders such as osteoarthritis and osteoporosis. To test the requirement for autophagy during skeletal development in zebrafish, we generated an atg13 CRISPR knockout zebrafish line. This line showed a complete loss of atg13 expression, and restricted autophagic activity in vivo. In the absence of autophagy, chondrocyte maturation was accelerated, with chondrocytes exhibiting signs of premature hypertrophy. Focussing on the jaw element, autophagy disruption affected joint articulation causing restricted mouth opening. This gross behavioural phenotype corresponded with a failure to thrive, and death in homozygote atg13 nulls within 17 days. Taken together, our results are consistent with autophagy contributing to the timely regulation of chondrocyte maturation and for extracellular matrix formation

Pembelajaran Tari Di SMP N 3 Mlati Dan SMA N 1 Seyegan (Studi Kasus: Sosialisasi Tari Peksi Eka Kapti Di Kabupaten Sleman)

Tari Peksi Eka Kapti merupakan tari yang terinspirasi dari satwa identitas Kabupaten Sleman yaitu Burung Punglor. Tarian ini diciptakan pada tahun 2014 oleh Mila Rosinta.Tari Peksi Eka Kapti adalah aktualisasi seekor burung sebagai simbol keseimbangan ekosistem dalam konteks satu kekuatan dan kebersamaan. Tarian ini diharapkan bisa diapresiasi masyarakat khususnya pelajar SD, SMP, dan SMK/SMA agar ikut berperan serta dalam upaya melestarikan aset identitas Kabupaten Sleman sebagai pembelajaran atau ekstra kurikuler di sekolah maupun di sanggar. Oleh sebab itu Pemerintah Kabupaten Sleman membuat sebuah program pengenalan dan pelestarian identitas daerah salah satunya dengan membuat sebuah karya tari yang inspirasinya dari Burung Punglor.Permasalahan yang ingin dikaji dalam penelitian ini adalah bagaimana pembelajaran tari di SMP N 3 Mlati dan SMA N 1 Seyegan (Studi Kasus: Sosialisasi Tari Peksi Eka Kapti di Kabupaten Sleman). Untuk membantu menemukan jawaban dari permasalahan adalah dengan menggunakan pendekatan multidisiplin sosiologi dan pendekatan koreografi. Tari Peksi Eka Kapti diajarkan di SMP N 3 Mlati dan SMA N 1 Seyegan sebagai sebuah ekstra kurikuler atau pengembangan diri sekolah dengan menggunakan metode-metode pengajaran yang cukup baik yaitu metode analisis, global, imitasi dan campuran yang diharapkan bahwa siswa yang berlatih bisa mencapai kualitas seperti yang dicontohkan. Strategi pembelajaran yang dilakukan kedua sekolah tersebut sama yaitu guru atau pengajar bercerita tentang tarian tersebut, memutar dokumentasi, mempraktekkan dan menjelaskan motif maupun transisi pada tarian (tahap penyampaian materi), memperkenalkan tehnik penjiwaan, pendalaman materi dan tahap yang terakhir adalah ujian hasil pembelajaran tari

Digital Interventions Supporting Self-care in People With Type 2 Diabetes Across Greater Manchester (Greater Manchester Diabetes My Way):Protocol for a Mixed Methods Evaluation

BACKGROUND: Type 2 Diabetes (T2D) is common, with a prevalence of approximately 7% of the population in the United Kingdom. The quality of T2D care is inconsistent across the United Kingdom, and Greater Manchester (GM) does not currently achieve the National Institute for Health and Care Excellence treatment targets. Barriers to delivery of care include low attendance and poor engagement with local T2D interventions, which tend to consist of programs of education delivered in traditional, face-to-face clinical settings. Thus, a flexible approach to T2D management that is accessible to people from different backgrounds and communities is needed. Diabetes My Way (DMW) is a digital platform that offers a comprehensive self-management and educational program that should be accessible to a wide range of people through mobile apps and websites. Building on evidence generated by a Scotland-wide pilot study, DMW is being rolled out and tested across GM. OBJECTIVE: The overarching objectives are to assess whether DMW improves outcomes for patients with T2D in the GM area, to explore the acceptability of the DMW intervention to stakeholders, and to assess the cost-effectiveness of the intervention. METHODS: A mixed methods approach will be used. We will take a census approach to recruitment in that all eligible participants in GM will be invited to participate. The primary outcomes will be intervention-related changes compared with changes observed in a matched group of controls, and the secondary outcomes will be within-person intervention-related changes. The cost-effectiveness analysis will focus on obtaining reliable estimates of how each intervention affects risk factors such as HbA1c and costs across population groups. Qualitative data will be collected via semistructured interviews and focus groups and organized using template analysis. RESULTS: As of May 10, 2021, a total of 316 participants have been recruited for the quantitative study and have successfully enrolled. A total of 278 participants attempted to register but did not have appropriate permissions set by the general practitioners to gain access to their data. In total, 10 participants have been recruited for the qualitative study (7 practitioners and 3 patients). An extension to recruitment has been granted for the quantitative element of the research, and analysis should be complete by December 2022. Recruitment and analysis for the qualitative study should be complete by December 2021. CONCLUSIONS: The findings from this study can be used both to develop the DMW system and improve accessibility and usability in more deprived populations generally, thus improving equity in access to support for T2D self-management. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/2623

The influence of 'significant others' on persistent back pain and work participation: a qualitative exploration of illness perceptions

Background Individual illness perceptions have been highlighted as important influences on clinical outcomes for back pain. However, the illness perceptions of 'significant others' (spouse/partner/close family member) are rarely explored, particularly in relation to persistent back pain and work participation. The aim of this study was to initiate qualitative research in this area in order to further understand these wider influences on outcome. Methods Semi-structured interviews based on the chronic pain version of the Illness Perceptions Questionnaire-Revised were conducted with a convenience sample of UK disability benefit claimants, along with their significant others (n=5 dyads). Data were analysed using template analysis. Results Significant others shared, and perhaps further reinforced, claimants' unhelpful illness beliefs including fear of pain/re-injury associated with certain types of work and activity, and pessimism about the likelihood of return to work. In some cases, significant others appeared more resigned to the permanence and negative inevitable consequences of the claimant's back pain condition on work participation, and were more sceptical about the availability of suitable work and sympathy from employers. In their pursuit of authenticity, claimants were keen to stress their desire to work whilst emphasising how the severity and physical limitations of their condition prevented them from doing so. In this vein, and seemingly based on their perceptions of what makes a 'good' significant other, significant others acted as a 'witness to pain', supporting claimants' self-limiting behaviour and statements of incapacity, often responding with empathy and assistance. The beliefs and responses of significant others may also have been influenced by their own experience of chronic illness, thus participants lives were often intertwined and defined by illness. Conclusions The findings from this exploratory study reveal how others and wider social circumstances might contribute both to the propensity of persistent back pain and to its consequences. This is an area that has received little attention to date, and wider support of these findings may usefully inform the design of future intervention programmes aimed at restoring work participation

Repetitive Behavior in Rubinstein–Taybi Syndrome:Parallels with Autism Spectrum Phenomenology

Syndrome specific repetitive behavior profiles have been described previously. A detailed profile is absent for Rubinstein–Taybi syndrome (RTS). The Repetitive Behaviour Questionnaire and Social Communication Questionnaire were completed for children and adults with RTS (N = 87), Fragile-X (N = 196) and Down (N = 132) syndromes, and individuals reaching cut-off for autism spectrum disorder (N = 228). Total and matched group analyses were conducted. A phenotypic profile of repetitive behavior was found in RTS. The majority of behaviors in RTS were not associated with social-communication deficits or degree of disability. Repetitive behavior should be studied at a fine-grained level. A dissociation of the triad of impairments might be evident in RTS