Social media influencers can be used to deliver positive information about the flu vaccine: findings from a multi-year study.

Large-scale digital flu vaccine campaigns have experienced difficulty increasing vaccination coverage among African Americans and Hispanics, and are routinely inundated by negative responses from vaccine opponents. A digital campaign employing user-generated content from social media 'micro' influencers who are predominantly followed by African Americans and Hispanics was implemented during the 2018-19 and 2019-20 flu seasons to disseminate positive information about the flu vaccine. At the time, this constituted the largest influencer-driven health campaign focused on these communities in the United States. Comments on posts were qualitatively coded to determine content perceptions among those exposed to posts. Digital metrics were also analyzed. During Year 1, posts reached 9 million+ social media users and generated 64 612 likes or shares, and 1512 responses. In Year 2, posts reached 8 million+ users and generated 155 600 likes or shares, and 3122 responses. Around 94% of public responses to posts were positive, suggesting this is a promising strategy to communicate health information and could shift social norms, particularly for heavily debated topics such as vaccination. This strategy represents a more community-led and participatory approach than most large-scale vaccination campaigns have attempted, with immediate applicability to communications about the COVID-19 vaccine.

FoxO1 induces apoptosis in skeletal myotubes in a DNA-binding-dependent manner.

Recent studies indicate that FoxO transcription factors play an important role in promoting muscle atrophy. To study mechanisms mediating effects of FoxO proteins on muscle wasting, FoxO1-estrogen receptor fusion proteins that are activated by treatment with 4-hydroxytamoxifen (4-OH-T) were stably transfected in C(2)C(12) skeletal myoblasts using the pBABE retroviral system and grown into multinucleated skeletal myotubes. Activation of FoxO1 resulted in significant muscle atrophy, which was accompanied by DNA fragmentation, evidenced by terminal deoxynucleotidyl transferase dUTP-mediated nick end labeling. Cells expressing a DNA-binding-deficient form of FoxO1 also exhibited significant atrophy on FoxO1 activation but no hallmark signs of apoptosis. FoxO1 activation resulted in a significant increase in muscle atrophy F-box (MAFbx)/atrogin-1, muscle-specific RING finger protein 1 (MuRF-1), and Bcl-2-interacting mediator of cell death (Bim) gene expression, with no significant increase in Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 (BNip3) gene expression. Although the ability of FoxO1 to induce MuRF-1 gene expression appeared to be independent of DNA binding, expression of MAFbx/atrogin-1 and Bim was significantly blunted in cells expressing DNA-binding-deficient FoxO1. BNip3 gene expression was significantly elevated in DNA-binding-deficient mutant cells. These findings indicate that FoxO1 promotes skeletal muscle atrophy through induction of proteolytic and apoptotic machinery via DNA-binding-dependent and -independent mechanisms.

COX-2 inhibitor reduces skeletal muscle hypertrophy in mice.

Anti-inflammatory strategies are often used to reduce muscle pain and soreness that can result from high-intensity muscular activity. However, studies indicate that components of the acute inflammatory response may be required for muscle repair and growth. The hypothesis of this study was that cyclooxygenase (COX)-2 activity is required for compensatory hypertrophy of skeletal muscle. We used the synergist ablation model of skeletal muscle hypertrophy, along with the specific COX-2 inhibitor NS-398, to investigate the role of COX-2 in overload-induced muscle growth in mice. COX-2 was expressed in plantaris muscles during compensatory hypertrophy and was localized mainly in or near muscle cell nuclei. Treatment with NS-398 blunted the increases in mass and protein content in overloaded muscles compared with vehicle-treated controls. Additionally, the COX-2 inhibitor decreased activity of the urokinase type plasminogen activator, macrophage accumulation, and cell proliferation, all of which are required for hypertrophy after synergist ablation. Expression of insulin-like growth factor-1 and phosphorylation of Akt, mammalian target of rapamycin, and p70S6K were increased following synergist ablation, but were not affected by NS-398. Additionally, expression of atrogin-1 was reduced during hypertrophy, but was also not affected by NS-398. These results demonstrate that COX-2 activity is required for skeletal muscle hypertrophy, possibly through facilitation of extracellular protease activity, macrophage accumulation, and cell proliferation.