Understanding which compounds comprising the complex and dynamic marine dissolved organic matter (DOM) pool are important in supporting heterotrophic bacterial production remains a major challenge. We eliminated sources of labile phytoplankton products, advected terrestrial material and photodegradation products to coastal microbial communities by enclosing water samples in situ for 24 h in the dark. Bacterial genes for which expression decreased between the beginning and end of the incubation and chemical formulae that were depleted over this same time frame were used as indicators of bioavailable compounds, an approach that avoids augmenting or modifying the natural DOM pool. Transport- and metabolism-related genes whose relative expression decreased implicated osmolytes, carboxylic acids, fatty acids, sugars and organic sulfur compounds as candidate bioreactive molecules. FT-ICR MS analysis of depleted molecular formulae implicated functional groups ~ 30-40 Da in size cleaved from semi-polar components of DOM as bioreactive components. Both gene expression and FT-ICR MS analyses indicated higher lability of compounds with sulfur and nitrogen heteroatoms. Untargeted methodologies able to integrate biological and chemical perspectives can be effective strategies for characterizing the labile microbial metabolites participating in carbon flux.

Moxibustion is an integral part of Traditional Chinese Medicine (TCM). It achieved higher level of recognition and had more general application in ancient times than in contemporary life. As the vital historical sources, the records of unearthed literatures offered precious insights to Chinese social life pattern and medical practice in Qin and Han dynasties (221 BC–220 AD). There was no surprise that the bamboo and silk documents excavated from Mawangdui (马王堆) tomb, Hantanpo (旱滩坡) tomb, and other relics had a large amount of texts relevant to moxibustion. This research sorted moxibustion recordings from seven unearthed literatures and discovered that moxibustion had been developed into different modalities and utilized to treat many diseases at that time. In addition, the indications, contraindications of moxibustion, and the method of postmoxibustion care were also discussed. On this basis, some hints were provided to support the hypothesis that the practice of moxibustion led to the discovery of meridians. All our preliminary results in the research have drawn attention for this old therapy and given a new source for its application in clinic and scientific research.

Objective. To investigate the antiaging effects of moxibustion and moxa smoke on APP/PS1 mice and to illustrate the mechanism of moxibustion improving Alzheimer’s disease (AD). Methods. 36 male APP/PS1 mice were randomly assigned into three groups (n = 12), including a model control group, a moxibustion group, and a moxa smoke group. In addition, 12 C57BL/6 normal mice served as a normal (negative) control group. Mice in the moxibustion group received moxibustion intervention using Guanyuan (RN4) acupoint. Mice in the moxa smoke group received moxa smoke exposure with the same frequency as the moxibustion group. Behavioral tests were implemented in the 9th week, 3 days after the completion of the intervention. Tricarboxylic acid cycle and fatty acid metabolomics assessments of the mice were determined after behavioral tests. Results. In this study, relative to normal mice, we found that AD mice showed altered tricarboxylic and fatty acid metabolism and showed behavioral changes consistent with the onset of AD. However, both the moxibustion and moxa smoke interventions were able to mitigate these effects to some degree in AD mice. Conclusions. The data suggest that tricarboxylic acid cycle and unsaturated fatty acid metabolomics changes may be a target of AD, and the beneficial effects of moxibustion on cognitive behaviors may be mediated by the energy metabolism system.

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Unsupervised clustering of intensive care unit (ICU) medications may identify unique medication clusters (i.e., pharmacophenotypes) in critically ill adults. We performed an unsupervised analysis with Restricted Boltzmann Machine of 991 medications profiles of patients managed in the ICU to explore pharmacophenotypes that correlated with ICU complications (e.g., mechanical ventilation) and patient-centered outcomes (e.g., length of stay, mortality). Six unique pharmacophenotypes were observed, with unique medication profiles and clinically relevant differences in ICU complications and patient-centered outcomes. While pharmacophenotypes 2 and 4 had no statistically significant difference in ICU length of stay, duration of mechanical ventilation, or duration of vasopressor use, their mortality differed significantly (9.0% vs. 21.9%, p < 0.0001). Pharmacophenotype 4 had a mortality rate of 21.9%, compared with the rest of the pharmacophenotypes ranging from 2.5-9%. Phenotyping approaches have shown promise in classifying the heterogenous syndromes of critical illness to predict treatment response and guide clinical decision support systems but have never included comprehensive medication information. This first-ever machine learning approach revealed differences among empirically-derived subgroups of ICU patients that are not typically revealed by traditional classifiers. Identification of pharmacophenotypes may enable enhanced decision making to optimize treatment decisions.

Background Elevated brain choline is associated with better executive function in preadolescents. Manipulating dietary choline prospectively in preadolescents using egg supplementation could improve executive function via effects on brain cellular and neurotransmitter function. Objective Test the 9-mo impact of egg supplementation on executive function. It was hypothesized that preadolescents who consumed meal/snack replacement products containing powder made from whole eggs would have the largest improvement in executive function after 9-mo compared to those consuming similar products with either added milk powder or gelatin as a placebo. Methods A randomized, parallel groups, double-blinded, placebo-controlled trial design was used. The executive function of 122 preadolescents (58 females) aged 9-13 was analyzed before and after the 9-mo intervention. Primary outcomes were three National Institutes of Health Toolbox-Cognitive Battery measures of executive function: mental flexibility, working memory and selective attention/inhibitory control. Participants were randomized to consume food products with either: (i) whole egg powder, (ii) milk powder, or (iii) gelatin as a placebo, all matched on macronutrient content and used as replacements for commonly consumed foods (i.e., waffles, pancakes, macaroni and cheese, ice cream, and brownies). Hypothesis testing used mixed-effects models that included physical activity and sleep scores as covariates. Results A statistically significant group by time interaction for selective attention and inhibitory control was found (p=0.049) for the milk group. This interaction resulted from no change for the placebo group and an improvement in selective attention and inhibitory control performance for the milk group by a T-score of 5.8; the effect size d was 0.44 standard deviation units. Other comparisons were statistically insignificant. Conclusions Consumption of foods with added milk powder as replacements for snacks or meals for 9-mo improves selective attention/inhibitory control in preadolescents. Replacement foods with added whole egg powder does not impact the 9-mo change in preadolescent executive function. This trial was registered at clinicaltrials.gov as NCT03739424.

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While medication regimen complexity, as measured by a novel medication regimen complexity-intensive care unit (MRC-ICU) score, correlates with baseline severity of illness and mortality, whether the MRC-ICU improves hospital mortality prediction is not known. After characterizing the association between MRC-ICU, severity of illness and hospital mortality we sought to evaluate the incremental benefit of adding MRC-ICU to illness severity-based hospital mortality prediction models. This was a single-center, observational cohort study of adult intensive care units (ICUs). A random sample of 991 adults admitted ≥ 24 h to the ICU from 10/2015 to 10/2020 were included. The logistic regression models for the primary outcome of mortality were assessed via area under the receiver operating characteristic (AUROC). Medication regimen complexity was evaluated daily using the MRC-ICU. This previously validated index is a weighted summation of medications prescribed in the first 24 h of ICU stay [e.g., a patient prescribed insulin (1 point) and vancomycin (3 points) has a MRC-ICU = 4 points]. Baseline demographic features (e.g., age, sex, ICU type) were collected and severity of illness (based on worst values within the first 24 h of ICU admission) was characterized using both the Acute Physiology and Chronic Health Evaluation (APACHE II) and the Sequential Organ Failure Assessment (SOFA) score. Univariate analysis of 991 patients revealed every one-point increase in the average 24-h MRC-ICU score was associated with a 5% increase in hospital mortality [Odds Ratio (OR) 1.05, 95% confidence interval 1.02–1.08, p = 0.002]. The model including MRC-ICU, APACHE II and SOFA had a AUROC for mortality of 0.81 whereas the model including only APACHE-II and SOFA had a AUROC for mortality of 0.76. Medication regimen complexity is associated with increased hospital mortality. A prediction model including medication regimen complexity only modestly improves hospital mortality prediction.