The Perfect Step is the first one: Improving the quality of life for patients with spinal cord injuries through structured exercise.

CONTEXT: More than 1 million people live with spinal cord injuries (SCI) in the United States alone. Despite research suggesting improvement in functional activities in patients who participate in regular physical activity, there is limited data on the specific impact of exercise as it pertains to patient-reported quality-of-life (QoL) measures of mood, pain, independence, or medical complications. Patients with SCI participating in a longitudinal exercise program at a community-based fitness facility (The Perfect Step) in Pomona, California were invited to participate in this study. This program consisted of at least two hours a week of exercise-based therapy, loadbearing, and neuroplasticity retraining for two years. Participants were asked to retrospectively rate patient-reported quality-of-life outcomes at the start of participation in the program, and at 6, 12, and 24 months after the program start as measured by an 89-item SCI QoL questionnaire covering domains including mood (39 items), pain (16 items), independence (7 items), bladder function (14 items), and pressure ulcers (13 items). 24 patients with SCI (16 cervical, 4 thoracic, 3 lumbar, 1 unspecified) were included in the final analysis. FINDINGS: Wilcoxon rank sum tests were used to compare patient-reported outcome measures over time. Patients reported statistically significantly improved outcomes across all domains at all timepoints to varying degrees, with improvement in 73/89 items at 6 months, 57/89 at 12 months, and 65/89 at 24 months after participation start (P < 0.05, all). CONCLUSION/CLINICAL RELEVANCE: Patients with SCI engaging in a structured exercise program demonstrated sustainable, longitudinal improvements in mood, pain control, independence, and fewer impairments related to bladder function and pressure ulcers. Physicians should consider the integration of structured exercise into the rehabilitation program alongside traditional medical care to optimize the quality of life for those with SCI. Future research should involve a direct comparison of QoL in patients with SCI participating in structured exercise versus those who are not.

Implementation of the Helping Babies Breathe Training Program: A Systematic Review.

CONTEXT: Helping Babies Breathe (HBB) is a well-established neonatal resuscitation program designed to reduce newborn mortality in low-resource settings. OBJECTIVES: In this literature review, we aim to identify challenges, knowledge gaps, and successes associated with each stage of HBB programming. DATA SOURCES: Databases used in the systematic search included Medline, POPLINE, Cumulative Index to Nursing and Allied Health Literature, Latin American and Caribbean Health Sciences Literature, African Index Medicus, Cochrane, and Index Medicus. STUDY SELECTION: All articles related to HBB, in any language, were included. Article quality was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation framework. DATA EXTRACTION: Data were extracted if related to HBB, including its implementation, acquisition and retention of HBB knowledge and skills, changes in provider behavior and clinical care, or the impact on newborn outcomes. RESULTS: Ninety-four articles met inclusion criteria. Barriers to HBB implementation include staff turnover and limited time or focus on training and practice. Researchers of several studies found HBB cost-effective. Posttraining decline in knowledge and skills can be prevented with low-dose high-frequency refresher trainings, on-the-job practice, or similar interventions. Impact of HBB training on provider clinical practices varies. Although not universal, researchers in multiple studies have shown a significant association of decreased perinatal mortality with HBB implementation. LIMITATIONS: In addition to not conducting a gray literature search, articles relating only to Essential Care for Every Baby or Essential Care for Small Babies were not included in this review. CONCLUSIONS: Key challenges and requirements for success associated with each stage of HBB programming were identified. Despite challenges in obtaining neonatal mortality data, the program is widely believed to improve neonatal outcomes in resource-limited settings.

Potent, Irreversible Inhibition of Human Carboxylesterases by Tanshinone Anhydrides Isolated from Salvia miltiorrhiza ("Danshen").

The roots of Salvia miltiorrhiza ("Danshen") have been used in Chinese herbal medicine for centuries for a host of different conditions. While the exact nature of the active components of this material are unknown, large amounts of tanshinones are present in extracts derived from these samples. Recently, the tanshinones have been demonstrated to be potent human carboxylesterase (CE) inhibitors, with the ability to modulate the biological activity of esterified drugs. During the course of these studies, we also identified more active, irreversible inhibitors of these enzymes. We have purified, identified, and synthesized these molecules and confirmed them to be the anhydride derivatives of the tanshinones. These compounds are exceptionally potent inhibitors ( Ki < 1 nM) and can inactivate human CEs both in vitro and in cell culture systems and can modulate the metabolism of the esterified drug oseltamivir. Therefore, the coadministration of Danshen extracts with drugs that contain the ester chemotype should be minimized since, not only is transient inhibition of CEs observed with the tanshinones, but also prolonged irreversible inhibition arises via interaction with the anhydrides.

Selective Inhibitors of Human Liver Carboxylesterase Based on a ß-Lapachone Scaffold: Novel Reagents for Reaction Profiling.

Carboxylesterases (CEs) are ubiquitous enzymes that are responsible for the metabolism of xenobiotics, including drugs such as irinotecan and oseltamivir. Inhibition of CEs significantly modulates the efficacy of such agents. We report here that ß-lapachone is a potent, reversible CE inhibitor with Ki values in the nanomolar range. A series of amino and phenoxy analogues have been synthesized, and although the former are very poor inhibitors, the latter compounds are highly effective in modulating CE activity. Our data demonstrate that tautomerism of the amino derivatives to the imino forms likely accounts for their loss in biological activity. A series of N-methylated amino derivatives, which are unable to undergo such tautomerism, were equal in potency to the phenoxy analogues and demonstrated selectivity for the liver enzyme hCE1. These specific inhibitors, which are active in cell culture models, will be exceptionally useful reagents for reaction profiling of esterified drugs in complex biological samples.