Inter-individual variations in circadian misalignment-induced NAFLD pathophysiology in mice.

Pathological consequences of circadian misalignment, such as shift work, show considerable individual differences, but the lack of mechanistic understanding hinders precision prevention to prevent and mitigate disease symptoms. Here, we employed an integrative approach involving physiological, transcriptional, and histological phenotypes to examine inter-individual differences in pre-symptomatic pathological progression, preceding irreversible disease onset, in wild-type mice exposed to chronic jet-lag (CJL). We observed that CJL markedly increased the prevalence of hepatic steatosis with pronounced inter-individual differences. Stratification of individual mice based on CJL-induced hepatic transcriptomic signature, validated by histopathological analysis, pinpoints dysregulation of lipid metabolism. Moreover, the period and power of intrinsic behavioral rhythms were found to significantly correlate with CJL-induced gene signatures. Together, our results suggest circadian rhythm robustness of the animals contributes to inter-individual variations in pathogenesis of circadian misalignment-induced diseases and raise the possibility that these physiological indicators may be available for predictive hallmarks of circadian rhythm disorders.

Effect of quantitative partial valgus stress during baseball pitching on ball velocity and subjective pitch-effort.

BACKGROUND: Excessive elbow valgus stress can often cause pitching elbow injuries, and rehabilitation is usually required before an athlete can resume playing. However, there is a lack of information on the partial load rehabilitation of pitching elbow injuries caused by valgus extension overload based on elbow valgus stress. The purpose of this study was to clarify how quantitative partial elbow valgus stress while pitching affects ball velocity and subjective pitch-effort. METHODS: Forty-six male baseball pitchers participated in this study. Each player wore a wearable device on the elbow that collected their pitch parameters. Ball velocity was measured using a radar gun. Each elbow valgus stress was measured while each player was instructed to throw 5 fastballs at full effort. Then, based on the average stress of the 5 throws (100% partial valgus stress), the 75% and 50% stresses were calculated (75% and 50% partial valgus stress, respectively). Each pitcher continued to pitch until the number of pitches thrown at the targeted elbow stress reached 5. Each player was asked about their subjective pitch-effort after completing each type of partial valgus stress pitch. Outcomes were statistically evaluated using either a 1-way repeated measures analysis of variance or 2-way analysis of variance. RESULTS: The ball velocity was 72% (95% confidence interval [CI], 69%-75%) and 58% (95% CI, 55%-61%) during the 75% and 50% partial valgus stress, respectively (P < .001). Subjective pitch-effort was 41% (95% CI, 38%-44%) and 19% (95% CI, 16%-22%) while pitching at 75% and 50% partial valgus stress, respectively (P < .001). CONCLUSIONS: It may be desirable to instruct pitchers to throw at less than 20% subjective pitch-effort of the max if they want to pitch at 50% partial valgus stress. Elbow valgus stress might correlate with ball velocity at 75% partial valgus stress pitch. These results could enable clinicians and coaches to perform safer return-to-throwing programs and prevent excessive load on the elbow.