Science for behavioral health systems change: evolving research-policy-public partnerships.

Potent partnerships among researchers, policymakers, and community members have potential to produce positive changes in communities on a range of topics, including behavioral health. The paper provides a brief illustrative review of such partnerships and then describes the development and evolution of one partnership in particular in Virginia. The origin of the partnership is traced, along with its founding vision, mission, and values. Some of its several projects are described, including (a) needs assessment for implementation of evidence-based programs (EBPs) pursuant to the Family First Prevention Services Act; (b) statewide fidelity monitoring of key EBPs; and (c) projects to synergize state investments in specific EBPs, like multisystemic therapy, functional family therapy, and high fidelity wraparound. The paper concludes with some themes around which the center has evolved to serve the state and its citizens more effectively.

Regioisomeric Spirobifluorene CANAL Ladder Polymers and Their Gas Separation Performance.

We synthesized and characterized two isomeric microporous hydrocarbon ladder polymers from catalytic arene norbornene annulation (CANAL) of regioisomeric bis-norbornene fused spirobifluorenes, where the ladder chains are connected either through the same fluorene unit or across two different fluorene units in spirobifluorene. This pair of isomeric polymers was used to investigate the effect of ladder macromolecular structures on the microporosity and transport properties. Both polymers form mechanically intact films with thermal stability up to 480 °C and relatively high BET surface areas. The polymer formed from 2,7-dibromospirobifluorene showed higher BET surface area and higher gas permeability than the polymer from 2,2'-dibromospirobifluorene despite similar intersegmental spacing as indicated by X-ray scattering. The aging behavior for both polymers followed the same trend as the previously reported CANAL-fluorene polymers, with dramatically increased permselectivities over time, resulting in gas separation performance above the 2008 upper bounds for H2/CH4 and O2/N2.

The role of digital mammographic surveillance for detection of asymptomatic recurrence in autologous flap reconstructions.

OBJECTIVE: To evaluate the utility of digital mammography in detecting asymptomatic malignancy in autologous flap reconstructions after mastectomy. METHODS: A retrospective database review identified all mammograms performed on asymptomatic patients with flap reconstructions over a 9-year period (1/1/2009 to 12/31/2017). A negative examination was defined as BI-RADS 1 or 2 and a positive examination was defined as BI-RADS 0, 4, or 5 assigned to the mastectomy side. Malignant outcomes were determined by pathology results. Interval cancers, or false negatives, were defined as locoregional malignant diagnosis within one year of a negative mammogram. Sensitivity, specificity, predictive values, abnormal interpretation rate, and cancer detection rate were calculated. RESULTS: 626 mammograms of asymptomatic flap reconstructions were performed in 183 patients. The most common flap type was TRAM (83.5 %, 523/626) and DIEP (13.4 %, 84/626). Most exams (98.2 %, 615/626) were negative, assessed as BI-RADS 1 or 2, with no interval cancers at follow-up. Eleven exams (1.8 %, 11/626) were positive, assessed as BI-RADS 0, 4, or 5. After diagnostic work-up of all BI-RADS 0 exams, 9 cases had a final recommendation for biopsy of which 3 were malignant. Mammography yielded a cancer detection rate of 0.5 % (3/626), abnormal interpretation rate of 1.8 % (11/626), NPV of 100 % (615/615), overall PPV of 27.3 % (3/11), PPV2 (positive predictive value of a biopsy recommendation) of 33.3 % (3/9), sensitivity of 100 % (3/3), and specificity of 98.7 % (615/623). CONCLUSION: Digital mammography of asymptomatic autologous flap reconstructions after mastectomy demonstrated high sensitivity and low abnormal interpretation rate. Cancer detection rate was comparable to current national benchmarks for mammographic screening in the general U.S. population without mastectomy.

Enhanced H2O2 Upcycling into Hydroxyl Radicals with GO/Ni:FeOOH-Coated Silicon Nanowire Photocatalysts for Wastewater Treatment.

There remains continued interest in improving the advanced water oxidation process [e.g., ultraviolet (UV)/hydrogen peroxide (H2O2)] for more efficient and environmentally friendly wastewater treatment. Here, we report the design, fabrication, and performance of graphene oxide (GO, on top)/nickel-doped iron oxyhydroxide (Ni:FeOOH, shell)/silicon nanowires (SiNWs, core) as a new multifunctional photocatalyst for the degradation of common pollutants like polystyrene and methylene blue through enhancing the hydroxyl radical (•OH) production rate of the UV/H2O2 system. The photocatalyst combines the advantages of a large surface area and light absorption characteristics of SiNWs with heterogeneous photo-Fenton active Ni:FeOOH and photocatalytically active/charge separator GO. In addition, the built-in electric field of GO/Ni:FeOOH/SiNWs facilitates the charge separation of electrons to GO and holes to Ni:FeOOH, thus boosting the photocatalytic performance. Our photocatalyst increases the •OH yield by 5.7 times compared with that of a blank H2O2 solution sample and also extends the light absorption spectrum to include visible light irradiation.

Human Cardiac Pericytes Are Susceptible to SARS-CoV-2 Infection.

COVID-19 is associated with serious cardiovascular complications, with incompletely understood mechanism(s). Pericytes have key functions in supporting endothelial cells and maintaining vascular integrity. We demonstrate that human cardiac pericytes are permissive to SARS-CoV-2 infection in organotypic slice and primary cell cultures. Viral entry into pericytes is mediated by endosomal proteases, and infection leads to up-regulation of inflammatory markers, vasoactive mediators, and nuclear factor kappa-B-dependent cell death. Furthermore, we present evidence of cardiac pericyte infection in COVID-19 myocarditis patients. These data demonstrate that human cardiac pericytes are susceptible to SARS-CoV-2 infection and suggest a role for pericyte infection in COVID-19.

Emerging technologies for genetic control systems in cellular therapies.

Progress in synthetic biology has enabled the construction of designer cells that sense biological inputs, and, in response, activate user-defined biomolecular programs. Such engineered cells provide unique opportunities for treating a wide variety of diseases. Current strategies mostly rely on cell-surface receptor systems engineered to convert binding interactions into activation of a transcriptional program. Genetic control systems are emerging as an appealing alternative to receptor-based sensors as they overcome the need for receptor engineering and result in cellular behaviors that operate over therapeutically relevant timescales. Genetic control systems include synthetic gene networks, RNA-based sensors, and post-translational tools. These technologies present fundamental challenges, including the requirement for precise integration with innate pathways, the need for parts orthogonal to existing circuitries, and the metabolic burden induced by such complex cell engineering endeavors. This review discusses the challenges in the design of genetic control systems for cellular therapies and their translational applications.

Introducing Wound Healing Assays in the Undergraduate Biology Laboratory Using Ibidi Plates.

The wound healing assay is a simple and inexpensive method that allows researchers to experimentally mimic cell growth and migration leading to wound healing. In this assay, a wound is created on a monolayer of cultured mammalian cells and cell migration is monitored. Micrographs are captured at regular intervals during the duration of the experiment. These microscopy images are analyzed to compare cell migration and wound closure under different conditions. Introduction of different cytotoxic treatments into a wound healing assay can provide information as to whether a particular drug or compound of interest has the ability to affect cell migration. This type of analysis is important when assessing the ability of a particular cancer cell line to display invasive and metastatic behaviors. One of the challenges of this assay is to create the original wound in a way that is consistent across plates or treatments, facilitating comparisons across experimental groups. This is a particular challenge when using the wound healing assay in the context of an undergraduate biology class to expose students to a distinct form of mammalian cell culture and help them apply scientific knowledge and research skills. We found an easy way to overcome this obstacle by using ibidi plates. In this article, we provide a simple protocol to use ibidi plates and HeLa cells to set up wound healing assays. This laboratory exercise allows undergraduate students to utilize different skills developed through cell culture experience, such as growing, treating, and imaging mammalian cells.

Hydrocarbon ladder polymers with ultrahigh permselectivity for membrane gas separations.

Membranes have the potential to substantially reduce energy consumption of industrial chemical separations, but their implementation has been limited owing to a performance upper bound-the trade-off between permeability and selectivity. Although recent developments of highly permeable polymer membranes have advanced the upper bounds for various gas pairs, these polymers typically exhibit limited selectivity. We report a class of hydrocarbon ladder polymers that can achieve both high selectivity and high permeability in membrane separations for many industrially relevant gas mixtures. Additionally, their corresponding films exhibit desirable mechanical and thermal properties. Tuning of the ladder polymer backbone configuration was found to have a profound effect on separation performance and aging behavior.

Wastewater bacteria remediating the pharmaceutical metformin: Genomes, plasmids and products.

Metformin is used globally to treat type II diabetes, has demonstrated anti-ageing and COVID mitigation effects and is a major anthropogenic pollutant to be bioremediated by wastewater treatment plants (WWTPs). Metformin is not adsorbed well by activated carbon and toxic N-chloro derivatives can form in chlorinated water. Most earlier studies on metformin biodegradation have used wastewater consortia and details of the genomes, relevant genes, metabolic products, and potential for horizontal gene transfer are lacking. Here, two metformin-biodegrading bacteria from a WWTP were isolated and their biodegradation characterized. Aminobacter sp. MET metabolized metformin stoichiometrically to guanylurea, an intermediate known to accumulate in some environments including WWTPs. Pseudomonas mendocina MET completely metabolized metformin and utilized all the nitrogen atoms for growth. Pseudomonas mendocina MET also metabolized metformin breakdown products sometimes observed in WWTPs: 1-N-methylbiguanide, biguanide, guanylurea, and guanidine. The genome of each bacterium was obtained. Genes involved in the transport of guanylurea in Aminobacter sp. MET were expressed heterologously and shown to serve as an antiporter to expel the toxic guanidinium compound. A novel guanylurea hydrolase enzyme was identified in Pseudomonas mendocina MET, purified, and characterized. The Aminobacter and Pseudomonas each contained one plasmid of 160 kb and 90 kb, respectively. In total, these studies are significant for the bioremediation of a major pollutant in WWTPs today.

Distress Screening Through Patient-Reported Outcomes Measurement Information System (PROMIS) at an Academic Cancer Center and Network Site: Implementation of a Hybrid Model.

PURPOSE: Cancer care guidelines recommend regular distress screening of patients, with approximately one in three patients with cancer experiencing significant distress. However, the implementation of such programs is variable and inconsistent. We sought to assess the feasibility of implementing a hybrid electronic and paper screening tool for distress in all patients coming to a large academic cancer center and an associated integrated network site. METHODS: Patients at an academic cancer center (Stanford Cancer Center) and its associated integrated network site received either an electronic or on-paper modified Patient-Reported Outcomes Measurement Information System-Global Health questionnaire, to assess overall health and distress. We used the Reach, Effectiveness, Adoption, Implementation, and Maintenance implementation framework to test and report on the feasibility of using this questionnaire. Iterative workflow changes were made to implement the questionnaire throughout the healthcare system, including processes to integrate with existing electronic health records. RESULTS: From June 2015 to December 2017, 53,954 questionnaires representing 26,242 patients were collected. Approximately 30% of the questionnaires were completed before the visit on an electronic patient portal. The number of patients meeting the positive screen threshold remained around 40% throughout the study period. Following assessment, there were 3,763 referrals to cancer supportive services. Of note, those with a positive screen were more likely to have a referral to supportive care (odds ratio, 6.4; 95% CI, 5.8 to 6.9; P < .0001). CONCLUSION: The hybrid electronic and on-paper use of a commonly available patient-reported outcome tool, Patient-Reported Outcomes Measurement Information System-Global Health, as a large-scale distress screening method, is feasible at a large integrated cancer center.

Filling in the Gaps in Metformin Biodegradation: a New Enzyme and a Metabolic Pathway for Guanylurea.

The widely prescribed pharmaceutical metformin and its main metabolite, guanylurea, are currently two of the most common contaminants in surface and wastewater. Guanylurea often accumulates and is poorly, if at all, biodegraded in wastewater treatment plants. This study describes Pseudomonas mendocina strain GU, isolated from a municipal wastewater treatment plant, using guanylurea as its sole nitrogen source. The genome was sequenced with 36-fold coverage and mined to identify guanylurea degradation genes. The gene encoding the enzyme initiating guanylurea metabolism was expressed, and the enzyme was purified and characterized. Guanylurea hydrolase, a newly described enzyme, was shown to transform guanylurea to one equivalent (each) of ammonia and guanidine. Guanidine also supports growth as a sole nitrogen source. Cell yields from growth on limiting concentrations of guanylurea revealed that metabolism releases all four nitrogen atoms. Genes encoding complete metabolic transformation were identified bioinformatically, defining the pathway as follows: guanylurea to guanidine to carboxyguanidine to allophanate to ammonia and carbon dioxide. The first enzyme, guanylurea hydrolase, is a member of the isochorismatase-like hydrolase protein family, which includes biuret hydrolase and triuret hydrolase. Although homologs, the three enzymes show distinct substrate specificities. Pairwise sequence comparisons and the use of sequence similarity networks allowed fine structure discrimination between the three homologous enzymes and provided insights into the evolutionary origins of guanylurea hydrolase.IMPORTANCE Metformin is a pharmaceutical most prescribed for type 2 diabetes and is now being examined for potential benefits to COVID-19 patients. People taking the drug pass it largely unchanged, and it subsequently enters wastewater treatment plants. Metformin has been known to be metabolized to guanylurea. The levels of guanylurea often exceed that of metformin, leading to the former being considered a "dead-end" metabolite. Metformin and guanylurea are water pollutants of emerging concern, as they persist to reach nontarget aquatic life and humans, the latter if it remains in treated water. The present study has identified a Pseudomonas mendocina strain that completely degrades guanylurea. The genome was sequenced, and the genes involved in guanylurea metabolism were identified in three widely separated genomic regions. This knowledge advances the idea that guanylurea is not a dead-end product and will allow for bioinformatic identification of the relevant genes in wastewater treatment plant microbiomes and other environments subjected to metagenomic sequencing.

Iron is a ligand of SecA-like metal-binding domains in vivo.

The ATPase SecA is an essential component of the bacterial Sec machinery, which transports proteins across the cytoplasmic membrane. Most SecA proteins contain a long C-terminal tail (CTT). In Escherichia coli, the CTT contains a structurally flexible linker domain and a small metal-binding domain (MBD). The MBD coordinates zinc via a conserved cysteine-containing motif and binds to SecB and ribosomes. In this study, we screened a high-density transposon library for mutants that affect the susceptibility of E. coli to sodium azide, which inhibits SecA-mediated translocation. Results from sequencing this library suggested that mutations removing the CTT make E. coli less susceptible to sodium azide at subinhibitory concentrations. Copurification experiments suggested that the MBD binds to iron and that azide disrupts iron binding. Azide also disrupted binding of SecA to membranes. Two other E. coli proteins that contain SecA-like MBDs, YecA and YchJ, also copurified with iron, and NMR spectroscopy experiments indicated that YecA binds iron via its MBD. Competition experiments and equilibrium binding measurements indicated that the SecA MBD binds preferentially to iron and that a conserved serine is required for this specificity. Finally, structural modeling suggested a plausible model for the octahedral coordination of iron. Taken together, our results suggest that SecA-like MBDs likely bind to iron in vivo.

Using The Cancer Genome Atlas as an Inquiry Tool in the Undergraduate Classroom.

Undergraduate students in the biomedical sciences are often interested in future health-focused careers. This presents opportunities for instructors in genetics, molecular biology, and cancer biology to capture their attention using lab experiences built around clinically relevant data. As biomedical science in general becomes increasingly dependent on high-throughput data, well-established scientific databases such as The Cancer Genome Atlas (TCGA) have become publicly available tools for medically relevant inquiry. The best feature of this database is that it bridges the molecular features of cancer to human clinical outcomes-allowing students to see a direct connection between the molecular sciences and their future professions. We have developed and tested a learning module that leverages the power of TCGA datasets to engage students to use the data to generate and test hypotheses and to apply statistical tests to evaluate significance.

Effects of In-Season Velocity- Versus Percentage-Based Training in Academy Rugby League Players.

PURPOSE: To compare the effects of velocity-based training (VBT) vs percentage-based training (PBT) on strength, speed, and jump performance in academy rugby league players during a 7-wk in-season mesocycle. METHODS: A total of 27 rugby league players competing in the Super League U19s Championship were randomized to VBT (n = 12) or PBT (n = 15). Both groups completed a 7-wk resistance-training intervention (2×/wk) that involved the back squat. The PBT group used a fixed load based on a percentage of 1-repetition maximum (1-RM), whereas the VBT group used a modifiable load based on individualized velocity thresholds. Biomechanical and perceptual data were collected during each training session. Back-squat 1-RM, countermovement jump, reactive strength index, sprint times, and back-squat velocity at 40-90% 1-RM were assessed pretraining and posttraining. RESULTS: The PBT group showed likely to most likely improvements in 1-RM strength and reactive strength index, whereas the VBT group showed likely to very likely improvements in 1-RM strength, countermovement jump height, and back-squat velocity at 40% and 60% 1-RM. Sessional velocity and power were most likely greater during VBT compared with PBT (standardized mean differences = 1.8-2.4), while time under tension and perceptual training stress were likely lower (standardized mean differences = 0.49-0.66). The improvement in back-squat velocity at 60% 1-RM was likely greater following VBT compared with PBT (standardized mean difference = 0.50). CONCLUSION: VBT can be implemented during the competitive season, instead of traditional PBT, to improve training stimuli, decrease training stress, and promote velocity-specific adaptations.

Radiologic Image-Guided Tube Stoma Insertion in Neonatal Short Bowel Syndrome: First Case Report in the Literature.

Background: The management of neonatal short bowel syndrome can be challenging, and it is critical that these babies are managed in a multidisciplinary team setting with specialists who are experienced in the complex management of these children. One of the surgical strategies, initially published by the Bianchi team in Manchester, UK, is controlled tissue expansion program (CTE) which is done via the insertion of catheters into the proximal and distal bowel in the form of tube stomas. The clamping of the proximal tube allows for an increase in length and circumferential diameter of the proximal bowel for a period of time, whilst the distal tube stoma allows for easy refeeding of proximal bowel contents into the distal bowel. Method: CTE is associated with the risk of dislodgement and exposing patients to further surgical procedures with the risk of losing more bowel length. This article describes a new method in the management of such a complication through a less invasive approach of an image-guided procedure by interventional radiologists. Conclusion: Radiologically guided tube stoma reinsertion in a child with ultrashort bowel syndrome is a promising technique and should be considered in a CTE program in the management of short bowel syndrome.

Coherent imaging using laser feedback interferometry with pulsed-mode terahertz quantum cascade lasers.

We report a coherent terahertz (THz) imaging system that utilises a quantum cascade laser (QCL) operating in pulsed-mode as both the source and detector. The realisation of a short-pulsed THz QCL feedback interferometer permits both high peak powers and improved thermal efficiency, which enables the cryogen-free operation of the system. In this work, we demonstrated pulsed-mode swept-frequency laser feedback interferometry experimentally. Our interferometric detection scheme not only permits the simultaneous creation of both amplitude and phase images, but inherently suppresses unwanted background radiation. We demonstrate that the proposed system utilising microsecond pulses has the potential to achieve 0.25 mega-pixel per second acquisition rates, paving the pathway to video frame rate THz imaging.

New therapeutic approaches and novel alternatives for organophosphate toxicity.

Organophosphate compounds (OPCs) are commonly used as pesticides and were developed as nerve agents for chemical warfare. Exposure to OPCs results in toxicity due to their covalent binding and inhibition of acetylcholinesterase (AChE). Treatment for toxicity due to OPC exposure has been largely focused on the reactivation of AChE by oxime-based compounds via direct nucleophilic attack on the phosphorous center. However, due to the disadvantages to existing oxime-based reactivators for treatment of OPC poisoning, we considered non-oxime mechanisms of reactivation. A high throughput screen of compound libraries was performed to discover previously unidentified reactivation compounds, followed by studies on their analogs. In the process, we discovered multiple non-oxime classes of compounds, the most robust of which we have already reported [1]. Herein, we report other classes of compounds we identified in our screen that are efficient at reactivation. During biochemical characterization, we also found some compounds with other activities that may inspire novel therapeutic approaches to OPC toxicity. Specifically, we found compounds that [1] increase the rate of substrate hydrolysis by AChE and, [2] protect the enzyme from inhibition by OPC. Further, we discovered that a subset of reactivator compounds recover activity from both AChE and the related enzyme butyrylcholinesterase (BuChE). We now report these compounds, their activities and discuss how each relates to therapeutic approaches that would provide alternatives to traditional oxime-based reactivation.

Fetal neuroimaging: an update on technical advances and clinical findings.

This paper is based on a literature review from 2011 to 2016. The paper is divided into two main sections. The first section relates to technical advances in fetal imaging techniques, including fetal motion compensation, imaging at 3.0 T, 3-D T2-weighted MRI, susceptibility-weighted imaging, computed tomography, morphometric analysis, diffusion tensor imaging, spectroscopy and fetal behavioral assessment. The second section relates to clinical updates, including cerebral lamination, migrational anomalies, midline anomalies, neural tube defects, posterior fossa anomalies, sulcation/gyration and hypoxic-ischemic insults.