Skeletal muscle-specific inducible AMPKα1/α2 knockout mice develop muscle weakness, glycogen depletion, and fibrosis that persists during disuse atrophy.

The 5' adenosine monophosphate-activated protein kinase (AMPK) is an important skeletal muscle regulator implicated as a possible therapeutic target to ameliorate the local undesired deconditioning of disuse atrophy. However, the muscle-specific role of AMPK in regulating muscle function, fibrosis, and transcriptional reprogramming during physical disuse is unknown. The purpose of this study was to determine how the absence of both catalytic subunits of AMPK in skeletal muscle influences muscle force production, collagen deposition, and the transcriptional landscape. We generated skeletal muscle-specific tamoxifen-inducible AMPKα1/α2 knockout (AMPKα-/-) mice that underwent 14 days of hindlimb unloading (HU) or remained ambulatory for 14 days (AMB). We found that AMPKα-/- during ambulatory conditions altered body weight and myofiber size, decreased muscle function, depleted glycogen stores and TBC1 domain family member 1 (TBC1D1) phosphorylation, increased collagen deposition, and altered transcriptional pathways. Primarily, pathways related to cellular senescence and mitochondrial biogenesis and function were influenced by the absence of AMPKα. The effects of AMPKα-/- persisted, but were not worsened, following hindlimb unloading. Together, we report that AMPKα is necessary to maintain skeletal muscle quality.NEW & NOTEWORTHY We determined that skeletal muscle-specific AMPKα knockout (KO) mice display functional, fibrotic, and transcriptional alterations before and during muscle disuse atrophy. We also observed that AMPKα KO drives muscle fibrosis and pathways related to cellular senescence that continues during the hindlimb unloading period.

A Cohort Study of the Diversity in Animated Films From 1937 to 2021: In a World Less Enchanted Can We Be More Encanto?

Background Exposure to gender stereotypes in the media can develop and reinforce these attitudes in children. Individuals who are overweight, have health conditions, or are from a minority ethnic group (IMEG) are both underrepresented and poorly portrayed in the media. Role models can raise the aspirations of young children both professionally and in taking ownership of their health. We aimed to assess how the portrayal and diversity of characters in Disney, Pixar, and Dreamworks animated films have changed over time. Method A cohort study of all main characters in Disney, Pixar, and Dreamworks feature-length, theatrical, animated films from 1937 to 2021 was conducted. The portrayal of characters (R-score divided into negative, neutral, and positive -1, 0, and 1, respectively) was scored. The proportion of individuals with certain protected characteristics (sex, increased body mass index, physical or mental health conditions, being from an IMEG or part of the lesbian, gay, bisexual, transexual, and queer community) was also recorded. Results In total, 116 films and 1,275 characters were included. From the 1930s to 2020s, the proportion of women in films increased (16.7% to 47.3%, p=0.008) and their representation was more positive (mean R-score = -0.10 (SD:0.692) versus 0.49 (SD:0.837), p<0.001, respectively). The portrayal of overweight individuals has improved to a neutral position (mean R-score: -0.67 to 0.0). Both physical and mental illnesses are better portrayed (mean R-score: -0.18 to 0.34, p=0.004 and 0.5 to 1.0, p= 0.019, respectively). IMEGs introduced in 1953 now play more than just negative roles (mean R-score = -1 to 0.76, p=0.008). There is only one explicitly stated homosexual character. The most diverse film is Encanto. Conclusion This is the first study to comprehensively assess the diversity of animated film characters. We have identified an improvement in diversity and the way diverse individuals are portrayed which we hope continues.

What are the clinical consequences of 'potential' coeliac disease?

BACKGROUND: There is limited data on the clinical consequences of potential coeliac disease (PCD). AIM: To compare the presentation of PCD with coeliac disease (CD). METHODS: A retrospective study of adult PCD patients (>18 years) was performed. Presenting manifestations, serology and HLA-DQ genotyping were compared to an age-at-diagnosis and sex-matched CD cohort. RESULTS: The PCD cohort comprised 84 patients (median age 37 years, 63% female). The majority of PCD patients were symptomatic at presentation (PCD 91.7% versus CD cohort 94.0%, p = 0.55). In total, 79.8% and 76.2% of the PCD and CD cohorts respectively reported ≥1 gastrointestinal symptoms at presentation (p = 0.58). Extraintestinal presentation was less common in PCD than CD (65.5% versus 79.8% respectively, p = 0.038). PCD patients had fewer haematinic deficiencies than those with CD (iron 21.4% versus 41.7%, p = 0.005, vitamin D 14.3% versus 27.4%, p = 0.037 and folate deficiency 7.1% versus 28.6%, p= <0.001.) Post-diagnosis, 67.5% of the PCD patients chose a GFD. One-third of the patients who continued to eat gluten developed villous atrophy. CONCLUSION: The presentation of PCD and CD differ; however, mild enteropathy does not necessarily equate to mild symptoms. The GFD appears to be advantageous in symptomatic PCD.