A Call for a Health Data-Informed Workforce Among Clinicians.

Unlabelled: A momentous amount of health data has been and is being collected. Across all levels of health care, data are driving decision-making and impacting patient care. A new field of knowledge and role for those in health care is emerging-the need for a health data-informed workforce. In this viewpoint, we describe the approaches needed to build a health data-informed workforce, a new and critical skill for the health care ecosystem.

Antibiotic-induced gut dysbiosis elicits gut-brain axis relevant multi-omic signatures and behavioral and neuroendocrine changes in a nonhuman primate model.

Emerging evidence indicates that antibiotic-induced dysbiosis can play an etiological role in the pathogenesis of neuropsychiatric disorders. However, most of this evidence comes from rodent models. The objective of this study was to evaluate if antibiotic-induced gut dysbiosis can elicit changes in gut metabolites and behavior indicative of gut-brain axis disruption in common marmosets (Callithrix jacchus) - a nonhuman primate model often used to study sociability and stress. We were able to successfully induce dysbiosis in marmosets using a custom antibiotic cocktail (vancomycin, enrofloxacin and neomycin) administered orally for 28 days. This gut dysbiosis altered gut metabolite profiles, behavior, and stress reactivity. Increase in gut Fusobacterium spp. post-antibiotic administration was a novel dysbiotic response and has not been observed in any rodent or human studies to date. There were significant changes in concentrations of several gut metabolites which are either neurotransmitters (e.g., GABA and serotonin) or have been found to be moderators of gut-brain axis communication in rodent models (e.g., short-chain fatty acids and bile acids). There was an increase in affiliative behavior and sociability in antibiotic-administered marmosets, which might be a coping mechanism in response to gut dysbiosis-induced stress. Increase in urinary cortisol levels after multiple stressors provides more definitive proof that this model of dysbiosis may cause disrupted communication between gut and brain in common marmosets. This study is a first attempt to establish common marmosets as a novel model to study the impact of severe gut dysbiosis on gut-brain axis cross-talk and behavior.

Effects of Parkin on the Mitochondrial Genome in the Heart and Brain of Mitochondrial Mutator Mice.

Mitochondrial dysfunction has been implicated in neurodegenerative diseases like Parkinson's disease (PD). This study investigates the role of Parkin, a protein involved in mitochondrial quality control, and strongly linked to PD, in the context of mitochondrial DNA (mtDNA) mutations. Mitochondrial mutator mice (PolgD257A/D257A ) (Polg) are used and bred with Parkin knockout (PKO) mice or mice with disinhibited Parkin (W402A). In the brain, mtDNA mutations are analyzed in synaptosomes, presynaptic neuronal terminals, which are far from neuronal soma, which likely renders mitochondria there more vulnerable compared with brain homogenate. Surprisingly, PKO results in reduced mtDNA mutations in the brain but increased control region multimer (CRM) in synaptosomes. In the heart, both PKO and W402A lead to increased mutations, with W402A showing more mutations in the heart than PKO. Computational analysis reveals many of these mutations are deleterious. These findings suggest that Parkin plays a tissue-dependent role in regulating mtDNA damage response, with differential effects in the brain and heart. Understanding the specific role of Parkin in different tissues may provide insights into the underlying mechanisms of PD and potential therapeutic strategies. Further investigation into these pathways can enhance the understanding of neurodegenerative diseases associated with mitochondrial dysfunction.

Local intraluminal delivery of a smooth muscle-targeted RNA ligand inhibits neointima growth in a porcine model of peripheral vascular disease.

Anti-proliferative agents have been the primary therapeutic drug of choice to inhibit restenosis after endovascular treatment. However, recent safety and efficacy concerns for patients who underwent peripheral artery disease revascularization have demonstrated the need for alternative therapeutics. The aim of this investigation was to investigate the efficacy of a cell-specific RNA aptamer inhibiting vascular smooth muscle cell proliferation and migration. First, the impact of the RNA aptamer (Apt 14) on the wound healing of primary cultured porcine vascular smooth muscle cells (VSMCs) was examined in response to a scratch wound injury. We then evaluated the effect of local luminal delivery of Apt 14 on neointimal formation in a clinically relevant swine iliofemoral injury model. In contrast with a non-selected control aptamer (NSC) that had no impact on VSMC migration, Apt 14 attenuated the wound healing of primary cultured porcine VSMCs to platelet-derived growth factor-BB. Histological analysis of the Apt 14-treated arteries demonstrated a significant reduction in neointimal area percent diameter stenosis compared with arteries treated with saline and NSC controls. The findings of this study suggest that aptamers can function as selective inhibitors and thus provide more fine-tuning to inhibit selective pathways responsible for neointimal hyperplasia.

Exploring the Readability of Ingredients Lists of Food Labels with Existing Metrics.

Healthy diet and dietary behaviors are key components in prevention of chronic disease and management of chronic illness. Nutritional literacy has been associated with dietary behaviors and consumer choice of healthy foods. Nutritional literacy can be measured, for example, by examining consumer food label use, but current research focuses largely on the Nutrition Facts panel of a food product. Ingredients lists are critical for communicating food composition but are relatively unstudied in existing literature. The goal of this work is to measure the readability of ingredients lists on branded food products in the United States using existing metrics. We examined ingredients lists for all 495,646 products listed in the USDA Food Data Central database using four existing readability measures for text written in natural language. Each of these indices approximates the grade level that would be expected to comprehend a text; comparatively, patient consent forms are considered acceptable at an 8th grade reading level or lower. We report a broad variability for in readability using different metrics: ingredients lists recorded at a 9th grade reading level or higher to comprehend are found at rates of 16.5% (Automated Reading Index) to 74.9% (Gunning-Fog Index). Ingredients lists recorded at a 10th grade reading level or higher to comprehend are found at rates of 84.2% (using FRE Index). These results demonstrate the need to further explore how ingredients lists can be measured for readability, both for the purposes of consumer understanding as well as for supporting future nutrition research involving text mining.

Microbial rhodoquinone biosynthesis proceeds via an atypical RquA-catalyzed amino transfer from S-adenosyl-L-methionine to ubiquinone.

Rhodoquinone (RQ) is a close analogue of ubiquinone (UQ) that confers diverse bacterial and eukaryotic taxa the ability to utilize fumarate as an electron acceptor in hypoxic conditions. The RquA protein, identified in a Rhodospirillum rubrum RQ-deficient mutant, has been shown to be required for RQ biosynthesis in bacteria. In this report, we demonstrate that RquA, homologous to SAM-dependent methyltransferases, is necessary and sufficient to catalyze RQ biosynthesis from UQ in vitro. Remarkably, we show that RquA uses SAM as the amino group donor in a substitution reaction that converts UQ to RQ. In contrast to known aminotransferases, RquA does not use pyridoxal 5'-phosphate (PLP) as a coenzyme, but requires the presence of Mn2+ as a cofactor. As these findings reveal, RquA provides an example of a non-canonical SAM-dependent enzyme that does not catalyze methyl transfer, instead it uses SAM in an atypical amino transfer mechanism.

The minimal clinically important change in the motor section of the Burke-Fahn-Marsden Dystonia Rating Scale for generalized dystonia: Results from deep brain stimulation.

BACKGROUND: The minimal clinically important difference (MCID) describes the smallest change in an outcome that is considered clinically meaningful. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) is the most frequently rating scale assessing the efficacy of deep brain stimulation therapy (DBS) for dystonia. To expand our understanding, we evaluated the MCID thresholds for the BFMDRS motor subscale (MS) using physician-reported outcomes. METHODS: We assessed the MCID thresholds for the BFMDRS using movement disorder specialist ratings of videotapes from patients with genetically determined dystonia (Tor1A and THAP1) who underwent bilateral globus pallidum internum (GPi) DBS. We calculated the effect size of the BFMDRS-MS change and determined the MCID thresholds using the Clinical Global Impression of Change (CGIC). RESULTS: Twelve participants with a median age at DBS of 44.5 (range:27-68) had baseline and follow-up BFMDRS-MS with a median post-DBS follow-up of 5.5 years. Based on descriptive analysis, patients with good improvement after DBS according to the CGIC [8/12 (67%)] had a median BFMDRS-MS score reduction of 77% [Interquartile range (IQR):66.2;91.0) with an effect size of 0.39, and those with non-improvement [4/12 (33%)], had a median BFMDRS-MS score reduction of 62% (IQR:36.6;83.6). CONCLUSIONS: Our MCID estimates can be utilized in clinical practice in judging clinical relevance. However, further larger, powered studies are needed to simultaneously determine and compare MCID using patient and physician-reported outcomes in segmental and generalized dystonia in genetic and non-genetic populations.

Host Identity and Geographic Location Significantly Affect Gastrointestinal Microbial Richness and Diversity in Western Lowland Gorillas (Gorilla gorilla gorilla) under Human Care.

The last few decades have seen an outpouring of gastrointestinal (GI) microbiome studies across diverse host species. Studies have ranged from assessments of GI microbial richness and diversity to classification of novel microbial lineages. Assessments of the "normal" state of the GI microbiome composition across multiple host species has gained increasing importance for distinguishing healthy versus diseased states. This study aimed to determine baselines and trends over time to establish "typical" patterns of GI microbial richness and diversity, as well as inter-individual variation, in three populations of western lowland gorillas (Gorilla gorilla gorilla) under human care at three zoological institutions in North America. Fecal samples were collected from 19 western lowland gorillas every two weeks for seven months (n = 248). Host identity and host institution significantly affected GI microbiome community composition (p < 0.05), although host identity had the most consistent and significant effect on richness (p = 0.03) and Shannon diversity (p = 0.004) across institutions. Significant changes in microbial abundance over time were observed only at Denver Zoo (p < 0.05). Our results suggest that individuality contributes to most of the observed GI microbiome variation in the study populations. Our results also showed no significant changes in any individual's microbial richness or Shannon diversity during the 7-month study period. While some microbial taxa (Prevotella, Prevotellaceae and Ruminococcaceae) were detected in all gorillas at varying levels, determining individual baselines for microbial composition comparisons may be the most useful diagnostic tool for optimizing non-human primate health under human care.

The Development of an ex vivo Flow System to Assess Acute Arterial Drug Retention of Cardiovascular Intravascular Devices.

Purpose: The goal of this study was to develop an ex vivo system capable of rapidly evaluating arterial drug levels in living, isolated porcine carotid arteries. Methods: A vascular bioreactor system was developed that housed a native porcine carotid artery under physiological flow conditions. The ex vivo bioreactor system was designed to quantify the acute drug transfer of catheter-based drug delivery devices into explanted carotid arteries. To evaluate our ex vivo system, a paclitaxel-coated balloon and a perfusion catheter device delivering liquid paclitaxel were utilized. At 1-h post-drug delivery, arteries were removed, and paclitaxel drug levels measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Parallel experiments were performed in a pig model to validate ex vivo measurements. Results: LC-MS/MS analysis demonstrated arterial paclitaxel levels of the drug-coated balloon-treated arteries to be 48.49 ± 24.09 ng/mg and the perfusion catheter-treated arteries to be 25.42 ± 9.74 ng/mg at 1 h in the ex vivo system. Similar results were measured in vivo, as arterial paclitaxel concentrations were measured at 59.23 ± 41.27 ng/mg for the drug-coated balloon-treated arteries and 23.43 ± 20.23 ng/mg for the perfusion catheter-treated arteries. Overall, no significant differences were observed between paclitaxel measurements of arteries treated ex vivo vs. in vivo. Conclusion: This system represents the first validated ex vivo pulsatile system to determine pharmacokinetics in a native blood vessel. This work provides proof-of-concept of a quick, inexpensive, preclinical tool to study acute drug tissue concentration kinetics of drug-releasing interventional vascular devices.

Pre-Clinical Investigation of Liquid Paclitaxel for Local Drug Delivery: A Pilot Study.

The purpose of this pilot study was to investigate the feasibility of a perfusion catheter to deliver liquid paclitaxel into arterial segments. A clinically relevant rabbit ilio-femoral injury model was utilized to determine the impact of liquid paclitaxel delivered locally into the vessel wall using a perfusion catheter at 1 h to 14 days. Treatment by two clinically available forms of liquid paclitaxel, a solvent-based (sb) versus an albumin-bound (nab), along with a control (uncoated balloons), were investigated. Pharmacokinetic results demonstrated an increase in the retention of the sb-paclitaxel versus the nab-paclitaxel at 1 h; however, no other differences were observed at days one, three, and seven. Histological findings at 14 days showed significantly less neointimal area in the sb-paclitaxel treated arteries as compared with the nab-paclitaxel and the uncoated balloon-treated arteries. Additionally, percent area stenosis was significantly less in the sb-paclitaxel group. These results support the concept of local liquid delivery of paclitaxel into the arterial segments.

A Network-Based Compartmental Model For The Spread Of Whooping Cough In Nebraska.

Outbreaks of pertussis have increased over the past few years, drawing the attention of health care providers. Un- derstanding the transmission mechanisms of contagious disease is critically important, but depends on many intricate factors including pathogen and host environment, exposed population, and their activities. In this work, we try to improve upon the prediction model for the exposed population. The number of whooping cough reported cases in Nebraska between 2000-2017 was gathered. The standard Susceptible-Exposed-Infected-Recovered (SEIR) model is used to predict the infected numbers. The results show that the SEIR model prediction for the number of infected indi- viduals is much higher than the actual number. To overcome this problem, the Network Based-SEIR model is proposed, and is able to estimate the number of infected more accurately than the classic SEIR model.

Forecasting the Spread of Mosquito-Borne Disease using Publicly Accessible Data: A Case Study in Chikungunya.

Mosquito-borne diseases account for multiple public health challenges in our modern world. The international health community has seen a number of mosquito-borne diseases come to the forefront in recent years, including West Nile virus, Chikungunya virus, and currently, Zika virus. Predicting the spread of mosquito-borne disease can aid early decision support for when and how to employ public health interventions within a community; however, accurate and fast predictions, months into the future, are difficult to achieve in urgent scenarios, particularly when little information is known about infection rates. New sources of information including social media have been proposed to accelerate the development of predictive models of disease progression. In this research, we adapted a previously described model for the spread of mosquito-borne disease using open intelligence sources. The novel implementation of a mixed-model for mosquito-borne disease was capable of being executed in minimal runtime. The results indicate that this model yields fast and relevant results with acceptable margins of error.

Ignorance or bias? Evaluating the ideological and informational drivers of communication gaps about climate change.

Does the relationship between media use and learning about climate change depend more on audiences' scientific literacy on their ideological biases? To answer this question, we evaluate both the knowledge gap and belief gap hypotheses as they relate to climate change. Results indicate belief gaps for news and entertainment content and a knowledge gap for edutainment content. Climate change knowledge among conservatives decreased with greater attention to political news, but increased with greater attention to science news. TV entertainment was associated with a significant decrease in knowledge about climate change among liberals to similar levels as conservatives. Edutainment was associated with a widening gap in knowledge based on respondents' scientific literacy. Implications for informal learning about controversial science through the media are discussed.

Do people with schizophrenia have difficulty anticipating pleasure, engaging in effortful behavior, or both?

Motivation deficits are common in schizophrenia, but little is known about underlying mechanisms, or the specific goals that people with schizophrenia set in daily life. Using neurobiological heuristics of pleasure anticipation and effort assessment, we examined the quality of activities and goals of 47 people with and 41 people without schizophrenia, utilizing ecological momentary assessment. Participants were provided cell phones and called 4 times a day for 7 days, and were asked about their current activities and anticipation of upcoming goals. Activities and goals were later coded by independent raters on pleasure and effort. In line with recent laboratory findings on effort computation deficits in schizophrenia, relative to healthy participants, people with schizophrenia reported engaging in less effortful activities and setting less effortful goals, which were related to patient functioning. In addition, patients showed some inaccuracy in estimating how difficult an effortful goal would be, which in turn was associated with lower neurocognition. In contrast to previous research, people with schizophrenia engaged in activities and set goals that were more pleasure-based, and anticipated goals as being more pleasurable than controls. Thus, this study provided evidence for difficulty with effortful behavior and not anticipation of pleasure. These findings may have psychosocial treatment implications, focusing on effort assessment or effort expenditure. For example, to help people with schizophrenia engage in more meaningful goal pursuits, treatment providers may leverage low-effort pleasurable goals by helping patients to break down larger, more complex goals into smaller, lower-effort steps that are associated with specific pleasurable rewards.

The chemical induction of seizures in psychiatric therapy: were flurothyl (indoklon) and pentylenetetrazol (metrazol) abandoned prematurely?

BACKGROUND: Camphor-induced and pentylenetetrazol-induced brain seizures were first used to relieve psychiatric illnesses in 1934. Electrical inductions (electroconvulsive therapy, ECT) followed in 1938. These were easier and less expensive to administer and quickly became the main treatment method. In 1957, seizure induction with the inhalant anesthetic flurothyl was tested and found to be clinically effective.For many decades, complaints of memory loss have stigmatized and inhibited ECT use. Many variations of electricity in form, electrode placement, dosing, and stimulation method offered some relief, but complaints still limit its use. METHODS: The experience with chemical inductions of seizures was reviewed based on searches for reports of each agent in Medline and in the archival files of original studies by the early investigators. FINDINGS: Camphor injections were inefficient and were rapidly replaced by pentylenetetrazol. These were effective but difficult to administer. Flurothyl inhalation-induced seizures were as clinically effective as electrical inductions with lesser effects on memory functions. Flurothyl inductions were discarded because of the persistence of the ethereal aroma and the fears induced in the professional staff that they might seize. CONCLUSIONS: Persistent complaints of memory loss plague electricity induced seizures. Flurothyl induced seizures are clinically as effective without the memory effects associated with electricity. Reexamination of seizure inductions using flurothyl in modern anesthesia facilities is encouraged to relieve medication-resistant patients with mood disorders and catatonia.

An integrated model of communication influence on beliefs.

How do people develop and maintain their beliefs about science? Decades of social science research exist to help us answer this question. The Integrated Model of Communication Influence on Beliefs presented here combines multiple theories that have considered aspects of this process into a comprehensive model to explain how individuals arrive at their scientific beliefs. In this article, we (i) summarize what is known about how science is presented in various news and entertainment media forms; (ii) describe how individuals differ in their choices to be exposed to various forms and sources of communication; (iii) discuss the implications of how individuals mentally process information on the effects of communication; (iv) consider how communication effects can be altered depending on background characteristics and motivations of individuals; and (v) emphasize that the process of belief formation is not unidirectional but rather, feeds back on itself over time. We conclude by applying the Integrated Model of Communication Influence on Beliefs to the complex issue of beliefs about climate change.

The influence of eating rate on satiety and intake among participants exhibiting high dietary restraint.

BACKGROUND: Studies show inconsistent results with regards to whether eating slower can enhance satiety and reduce intake in a meal. Some methodological differences are apparent and could potentially explain why results are not consistent across studies. OBJECTIVE: To determine whether eating slower can enhance satiety and reduce intake when rate of eating is manipulated and not manipulated in a kitchen setting using a sample of participants who exhibit high dietary restraint (HDR). DESIGN: Two samples of college students who exhibit HDR, which is a group likely to use behavioral strategies to manage intake, were selected in a prescreening session. Participants were told how fast or slow to eat (Variation 1) or allowed to eat at their own pace (Variation 2). Self-reported satiety during the meal and amount consumed was recorded. The types of foods, macronutrient intakes, weights of foods, order of food intakes, and the dimensions of foods were held constant between groups to control for group differences in the sensory and hedonic qualities of the meals. RESULTS: Eating slower enhanced mid-meal satiety ratings, but only when instructions were given to eat fast or slow (Variation 1). In both variations, eating slower did not reduce amount consumed in the meal, although each variation had sufficient power to detect differences. CONCLUSION: Eating slower is not likely to be an effective strategy to control intake in a meal among those exhibiting HDR.