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The best models exhibited internal consistency and could reasonably predict the inhibitory activity against both PfNMT (HQSAR q2 /r2 /r2 pred = 0.83/0.98/0.81; CoMFA q2 /r2 /r2 pred = 0.78/0.97/0.86; CoMSIA q2 /r2 /r2 pred = 0.74/0.95/0.82) and HsNMT (HQSAR q2 /r2 /r2 pred = 0.79/0.93/0.74; CoMFA q2 /r2 /r2 pred = 0.82/0.98/0.60; CoMSIA q2 /r2 /r2 pred = 0.62/0.95/0.56). The results enabled the identification of the polar interactions (electrostatic and hydrogen-bonding properties) as the major molecular features that affected the inhibitory activity and selectivity. These findings should be useful for the design of PfNMT inhibitors with high affinities and selectivities as antimalarial lead candidates. © 2020 Wiley Periodicals, Inc.Developing strategies to improve retention in home visiting programs is critical to their success. The purpose of the study is to examine how the content provided during home visits moderates the association between family risks (economic, household functioning, and conflict) and retention in services. Parents (n = 1,322) voluntarily enrolled in Healthy Families America (n = 618) and Parents as Teachers (n = 704). Family characteristics were collected using the Family Map Inventories. Multilevel analyses showed a moderating impact of the time home visitors spent supporting parent-child interaction for all family risks examined. Moderating effects demonstrated a stronger positive association between focusing on the parent-child relationship and retention at 6 and 12 months for parents demonstrating greater needs. There were no moderating effects of child development content or case management activities with retention at 6 and 12 months. Together, families were more likely to stay in services when home visitors focused on parent-child interaction and child development, but less likely retained with more case management. Parents with greater risks were more likely to remain in services with more time focused on supporting parent-child interactions. Findings suggest the need to support our home visiting workforce in their work to promote healthy parent-child relationships. © 2020 Michigan Association for Infant Mental Health.KEY POINTS During maximal exercise, skeletal muscle metabolism and oxygen consumption remain elevated despite precipitous declines in power. Presently, it is unclear whether these responses are caused by an increased ATP cost of force generation (ATPCOST) or mitochondrial uncoupling, a process that reduces the efficiency of oxidative ATP synthesis (ATPOX). To address this gap, we used 31-phosphorus magnetic resonance spectroscopy to measure changes in ATPCOST and ATPOX in human quadriceps during repeated trials of maximal-intensity knee extensions lasting up to 4 min. ATPCOST remained unchanged. In contrast, ATPOX plateaued by ∼2 min and then declined (∼15%) over the final 2 min. The maximal capacity for ATPOX (Vmax), as well as ADP-specific rates of ATPOX, were also significantly diminished. Collectively, these results suggest that mitochondrial uncoupling, and not increased ATPCOST, is responsible for altering the regulation of skeletal muscle metabolism and oxygen consumption during maximal exercise. ABSTRt change over time (main-effect p = 0.45). ATPOX plateaued from 60-120 s and then decreased over the final 120 s (main-effect p = 0.001). The maximal capacity for oxidative ATP synthesis (Vmax ), as well as ADP-specific rates of ATPOX , also decreased over time (main-effect p = 0.001, both). Collectively, these results demonstrate that prolonged maximal contraction protocols impair oxidative energetics and implicate mitochondrial uncoupling as the mechanism for this response. The causes of mitochondrial uncoupling are presently unknown but may offer a potential explanation for the dissociation between skeletal muscle power output and oxygen consumption during maximal, all-out exercise protocols. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.OBJECTIVE To assess the risk of Alzheimer's disease (AD) in patients with obstructive sleep apnea (OSA) with or without treatment based on real-world evidence. STUDY DESIGN Retrospective cohort study. METHODS Patients newly diagnosed with OSA during 1997-2012 were identified using the National Health Insurance Research Database of Taiwan. Patients without OSA were randomly selected and matched in a 14 ratio by age, sex, urbanization level, and income. All patients were followed up until death or the end of 2013. The primary outcome was AD occurrence. RESULTS This study included 3,978 OSA patients and 15,912 non-OSA patients. OSA was independently and significantly associated with a higher incidence of AD in an adjusted Cox proportional hazard model (adjusted hazard ratio 2.12; 95% confidence interval [CI], 1.27-3.56). The average period of AD detection from the time of OSA occurrence was 5.44 years (standard deviation 2.96). Subgroup analyses revealed that the effect of OSA remained significant in patients aged ≥60 years, male subgroups, patients without CPAP or surgical treatment, and patients without pharmacological therapies. Patients with OSA who received treatment (continuous positive airway pressure or surgery) exhibited a significantly reduced risk of AD compared with those without treatment (incidence rate ratio 0.23, 95% CI, 0.06-0.98). CONCLUSION OSA is independently associated with an increased risk of AD. Selleckchem Teniposide Treatment for OSA reduces the AD risk in OSA patients. AD irreversibility renders OSA as a potential modifiable target for slowing or preventing the process of AD development. LEVEL OF EVIDENCE IV Laryngoscope, 2020. © 2020 The American Laryngological, Rhinological and Otological Society, Inc.Young children of color-especially boys-are at disproportionate risk for suspension and expulsion from early care and education settings. Infant and Early Childhood Mental Health Consultation (IECMHC) is an approach associated with lower than expected expulsion rates, but the mechanisms through which it may influence preschool expulsion are unknown. This paper reflects on the parallels between IECMHC and interventions created to reduce implicit bias. Based on interviews with leaders in IECMHC practice, implementation, and evaluation, a theoretical framework was created to articulate how IECMHC is hypothesized to affect expulsion by first reducing the influence of implicit bias on disciplinary decisions. Implications for practice and research are provided. © 2020 Michigan Association for Infant Mental Health.