Toward Precision Medicine: Circadian Rhythm of Blood Pressure and Chronotherapy for Hypertension - 2021 NHLBI Workshop Report.

Healthy individuals exhibit blood pressure variation over a 24-hour period with higher blood pressure during wakefulness and lower blood pressure during sleep. Loss or disruption of the blood pressure circadian rhythm has been linked to adverse health outcomes, for example, cardiovascular disease, dementia, and chronic kidney disease. However, the current diagnostic and therapeutic approaches lack sufficient attention to the circadian rhythmicity of blood pressure. Sleep patterns, hormone release, eating habits, digestion, body temperature, renal and cardiovascular function, and other important host functions as well as gut microbiota exhibit circadian rhythms, and influence circadian rhythms of blood pressure. Potential benefits of nonpharmacologic interventions such as meal timing, and pharmacologic chronotherapeutic interventions, such as the bedtime administration of antihypertensive medications, have recently been suggested in some studies. However, the mechanisms underlying circadian rhythm-mediated blood pressure regulation and the efficacy of chronotherapy in hypertension remain unclear. This review summarizes the results of the National Heart, Lung, and Blood Institute workshop convened on October 27 to 29, 2021 to assess knowledge gaps and research opportunities in the study of circadian rhythm of blood pressure and chronotherapy for hypertension.

Injury and Illness Surveillance During the 2016 Department of Defense Warrior Games: Review of Methods and Results.

INTRODUCTION: Surveillance systems have become a valuable tool to capture epidemiological data at multi-sport events, with findings serving to predict and prevent injury, reduce illness, and guide efficient utilization of medical resources. In 2016, the first injury and illness surveillance tool for the Department of Defense (DoD) Warrior Games was established to inform the required medical footprint. The purpose of this paper is to describe the methods and findings from the 2016 DoD Warrior Games surveillance system, which included a database of injuries and illness. MATERIALS AND METHODS: A total of 245 wounded warrior (WW) athletes were followed over 19 days, to include train-up and competition periods, as they competed for their respective teams of Army, Navy, Air Force, Marines, Special Operations, and United Kingdom. Medical personnel recorded injuries and illnesses treated utilizing a standardized surveillance form and data were entered into a daily tracker to examine patterns or areas for prevention. Reports included sex, age, event discipline, previous injury or illness, reason for presentation, and treatment provided. RESULTS: From June 3 to June 21, 2016, 114 individual encounters were recorded on the standard form and entered into the surveillance database. Athletes accounted for 67% of all encounters. Illness accounted for 30.7% of all visits, while injuries accounted for 69.2%. The incident proportion of injuries in athletes was 23.3 injuries per 100 athletes (95% CI 17.6, 30.1) and incident rate of 12.2 injuries per 1000 athlete days. Integrative medicine treatments including acupuncture, osteopathic manipulative treatment (OMT), massage therapy, and gua sha accounted for the largest forms of treatment (31%). CONCLUSIONS: From the surveillance data, staff levels and treatment supplies can be adjusted. In addition an improved surveillance tool can be created. Continuous surveillance is required to provide information on trends in injury and illness to support prevention strategies.

HIV-1 Protease Uses Bi-Specific S2/S2' Subsites to Optimize Cleavage of Two Classes of Target Sites.

Retroviral proteases (PRs) have a unique specificity that allows cleavage of sites with or without a P1' proline. A P1' proline is required at the MA/CA cleavage site due to its role in a post-cleavage conformational change in the capsid protein. However, the HIV-1 PR prefers to have large hydrophobic amino acids flanking the scissile bond, suggesting that PR recognizes two different classes of substrate sequences. We analyzed the cleavage rate of over 150 combinations of six different HIV-1 cleavage sites to explore rate determinants of cleavage. We found that cleavage rates are strongly influenced by the two amino acids flanking the amino acids at the scissile bond (P2-P1/P1'-P2'), with two complementary sets of rules. When P1' is proline, the P2 side chain interacts with a polar region in the S2 subsite of the PR, while the P2' amino acid interacts with a hydrophobic region of the S2' subsite. When P1' is not proline, the orientations of the P2 and P2' side chains with respect to the scissile bond are reversed; P2 residues interact with a hydrophobic face of the S2 subsite, while the P2' amino acid usually engages hydrophilic amino acids in the S2' subsite. These results reveal that the HIV-1 PR has evolved bi-functional S2 and S2' subsites to accommodate the steric effects imposed by a P1' proline on the orientation of P2 and P2' substrate side chains. These results also suggest a new strategy for inhibitor design to engage the multiple specificities in these subsites.