Objective The management of infected aortic endografts is a challenging endeavor. Treatment of this problem has not been well defined as it is fairly uncommon. However, the incidence is increasing. ...This study examines the results of treatment at a single center for this morbid process. Methods A retrospective review was performed of patients treated for infected abdominal or thoracic endograft infection following previous abdominal or thoracic endovascular aneurysm repair. Data was reviewed for patient demographics, details of initial endograft implantation, presentation and timeline of subsequent infection, management of infected grafts, and outcomes during follow-up. Results Overall, 18 patients were treated for infected endografts (thoracic: six, abdominal:12). Three patients were treated between 2000 and 2006, corresponding to a 0.6% institutional incidence of endograft infection (3/473). There were no transfers for infected endografts from outside institutions. From 2006 to 2011, 15 patients underwent treatment. Six were institutional cases of infections (6/945, 0.6% infection rate), however, there was an increase in transfers (n = 9). Median time to presentation with infection from endograft implant was 90 days, with over one-half (61%) presenting within the first 3 months. Tissue and/or blood cultures were positive in 12/16 growing Escherichia coli (n = 1), group A streptococcus (n = 3), methicillin-resistant Staphylococcus aureus (n = 3), or polymicrobial infections (n = 7). The other four patients were culture negative with computed tomography evidence of gas surrounding the endograft and clinical sepsis. Ten patients (abdominal: eight, thoracic: two) were treated with endograft explantation. The remaining eight patients were considered too high-risk for explant or refused open surgery and were therefore managed conservatively without explant (abdominal: four, thoracic: four). At a mean follow-up of 24.7 months, aneurysm-related mortality was 38.9% (n = 7) and was higher for patients presenting with aortoenteric or aortobronchial fistulas (n = 6/10, 60%) ( P = .04) and for thoracic stent infections (n = 5/6; 83%) ( P = .03). The only survivor of a thoracic infection was managed surgically. Overall survival for patients with abdominal endografts (n = 12) was similar between the eight patients managed surgically (n = 6/8; 75%) and the four selected for medical management (n = 4/4; 100%) ( P = .39). All survivors remain on long-term suppressive antibiotics. Two additional patients died of unrelated causes during follow-up. Conclusions Endograft infection is a rare but increasing complication after abdominal or thoracic endovascular aneurysm repair, which carries significant associated morbidity and mortality. Most endograft infections occurred in proximity to other types of infection, suggesting that bacterial seeding of the endograft was the source. Aortoenteric and aortobronchial fistulas are common presentations, which portend a significantly worse prognosis. Thoracic endograft infections, which have the highest rate of fistulization, have the worst outcomes. Surgical excision continues to be standard of care but conservative management with intravenous antibiotics may be of benefit in certain patients with abdominal endograft infections.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The rapid increase of the potent greenhouse gas methane in the atmosphere creates great urgency to develop and deploy technologies for methane mitigation. One approach to removing methane is to use ...bacteria for which methane is their carbon and energy source (methanotrophs). Such bacteria naturally convert methane to CO
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and biomass, a value-added product and a cobenefit of methane removal. Typically, methanotrophs grow best at around 5,000 to 10,000 ppm methane, but methane in the atmosphere is 1.9 ppm. Air above emission sites such as landfills, anaerobic digestor effluents, rice paddy effluents, and oil and gas wells contains elevated methane in the 500 ppm range. If such sites are targeted for methane removal, technology harnessing aerobic methanotroph metabolism has the potential to become economically and environmentally viable. The first step in developing such methane removal technology is to identify methanotrophs with enhanced ability to grow and consume methane at 500 ppm and lower. We report here that some existing methanotrophic strains grow well at 500 ppm methane, and one of them,
Methylotuvimicrobium buryatense
5GB1C, consumes such low methane at enhanced rates compared to previously published values. Analyses of bioreactor-based performance and RNAseq-based transcriptomics suggest that this ability to utilize low methane is based at least in part on extremely low non-growth-associated maintenance energy and on high methane specific affinity. This bacterium is a candidate to develop technology for methane removal at emission sites. If appropriately scaled, such technology has the potential to slow global warming by 2050.
Chemical-genetic interactions-observed when the treatment of mutant cells with chemical compounds reveals unexpected phenotypes-contain rich functional information linking compounds to their cellular ...modes of action. To systematically identify these interactions, an array of mutants is challenged with a compound and monitored for fitness defects, generating a chemical-genetic interaction profile that provides a quantitative, unbiased description of the cellular function(s) perturbed by the compound. Genetic interactions, obtained from genome-wide double-mutant screens, provide a key for interpreting the functional information contained in chemical-genetic interaction profiles. Despite the utility of this approach, integrative analyses of genetic and chemical-genetic interaction networks have not been systematically evaluated. We developed a method, called CG-TARGET (Chemical Genetic Translation via A Reference Genetic nETwork), that integrates large-scale chemical-genetic interaction screening data with a genetic interaction network to predict the biological processes perturbed by compounds. In a recent publication, we applied CG-TARGET to a screen of nearly 14,000 chemical compounds in Saccharomyces cerevisiae, integrating this dataset with the global S. cerevisiae genetic interaction network to prioritize over 1500 compounds with high-confidence biological process predictions for further study. We present here a formal description and rigorous benchmarking of the CG-TARGET method, showing that, compared to alternative enrichment-based approaches, it achieves similar or better accuracy while substantially improving the ability to control the false discovery rate of biological process predictions. Additional investigation of the compatibility of chemical-genetic and genetic interaction profiles revealed that one-third of observed chemical-genetic interactions contributed to the highest-confidence biological process predictions and that negative chemical-genetic interactions overwhelmingly formed the basis of these predictions. We also present experimental validations of CG-TARGET-predicted tubulin polymerization and cell cycle progression inhibitors. Our approach successfully demonstrates the use of genetic interaction networks in the high-throughput functional annotation of compounds to biological processes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
High quality DNA design tools are becoming increasingly important as synthetic biology continues to increase the rate and throughput of building and testing genetic constructs. To make effective use ...of expanded build and test capacity, genotype design tools must not only be efficient enough to allow for many designs to be easily created, but also expressive enough to support the complex design patterns required by scientists on the frontier of genome engineering. Genotype Specification Language (GSL) is a language-based design tool invented at Amyris that enables scientists to quickly create DNA designs using a familiar syntax. This syntax provides a layer of abstraction that moves users away from reading and writing raw DNA sequences toward composing designs in terms of functional parts . GSL increases the speed at which scientists can design DNA constructs, provides a precise and reproducible representation of parts, and achieves these goals while maintaining design flexibility. Finally, the GSL compiler can emit information such as the exact final DNA sequence of the design as well as the reagents (primers and template information) required to physically build the constructs. Since its open-source release in February 2016, the GSL compiler can be freely downloaded and used by genome engineers to efficiently specify genetic designs. This chapter briefly introduces GSL syntax and design principles before examining specific examples of genome engineering tasks with accompanying GSL code.
Background. In the northeastern United States, tick-borne diseases are a major public health concern. In controlled studies, a single springtime application of acaricide has been shown to kill ...68%-100% of ticks. Although public health authorities recommend use of acaricides to control tick populations in yards, the effectiveness of these pesticides to prevent tick bites or human tick-borne diseases is unknown. Methods. We conducted a 2-year, randomized, double-blinded, placebo-controlled trial among 2727 households in 3 northeastern states. Households received a single springtime barrier application of bifenthrin or water according to recommended practices. Tick drags were conducted 3-4 weeks after treatment on 10% of properties. Information on human-tick encounters and tick-borne diseases was collected through monthly surveys; reports of illness were validated by medical record review. Results. Although the abundance of questing ticks was significantly lower (63%) on acaricide-treated properties, there was no difference between treatment groups in human-tick encounters, self-reported tick-borne diseases, or medical-record-validated tickborne diseases. Conclusions. Used as recommended, acaricide barrier sprays do not significantly reduce the household risk of tick exposure or incidence of tick-borne disease. Measures for preventing tick-borne diseases should be evaluated against human outcomes to confirm effectiveness.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Adjustment disorder (AD) is one of the most commonly diagnosed mental health disorders and is generally conceptualized to be mild and short-lived. Despite the frequent use of AD in clinical settings, ...little is known about the prognosis of this condition. Our goal was to systematically review research on a range of AD outcomes in order to provide a broad characterization of AD prognosis. We conducted searches in MEDLINE, EMBASE, and PsycINFO. We included 31 cohort or randomized controlled trials with a total of 1,385,358 participants. Many patients maintained an AD diagnosis or were diagnosed with another mental health disorder months to years after initial diagnosis. Patients with AD tended to show symptom improvement at higher rates and to utilize less treatment than did patients with other disorders. AD-diagnosed groups experienced subsequent development of numerous physical conditions, such as infection, cancers, Parkinson's disease, and cardiovascular events, at higher rates than did control groups. Results were mixed regarding suicidality and occupational impairment. We rated most studies as having a moderate risk of bias. Based on limited findings, AD appears to progress as a milder disorder than do other disorders, but it not uncommonly transitions to more severe mental health states and may predict the development of future health issues, both mental and physical. Future prospective research that conforms to prognosis study guidelines is needed to better understand the course of this common disorder.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To date, no research has systematically evaluated screening instruments for gambling disorder to assess their accuracy and the quality of the research. This systematic review evaluated screening ...instruments for gambling disorder to inform decision makers about choices for population-level screening.
On May 22, 2017 and January 4, 2019, we searched PubMed, PsycInfo, EMBASE, and Cochrane for studies that evaluated screening instruments for gambling disorder. Studies were included if (1) the screening instrument was in English, (2) the screening instrument was compared to a reference standard semistructured interview based on Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases diagnoses of gambling disorder, and (3) data were reported on psychometric properties of the instrument.
We identified 31 different screening instruments from 60 studies. Only three instruments from three separate studies were eligible for inclusion in the systematic review.
Few screening instruments for gambling disorder have been validated with sufficient methodological quality to be recommended for use across a large health system.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•A systematic review on predictors of adjustment disorders identified 70 studies.•Gender, employment, and stress predicted adjustment disorders.•Social support and psychiatric history were also ...revealed as predictors.•Younger age predicted adjustment disorders versus another mental health condition.•Predictors of adjustment disorders were compared to PTSD, depression, and anxiety.
The diagnosis of adjustment disorder is common in clinical practice, yet there is lack of research on the etiology and epidemiology of adjustment disorders. The goal of this systematic review was to evaluate predictors of adjustment disorders in adults.
We conducted systematic searches in MEDLINE, EMBASE, and PsycINFO. We included 70 studies that examined thirteen theoretically-derived and predefined predictors of adjustment disorders with a total of 3,449,374 participants.
We found that female gender, younger age, unemployed status, stress, physical illness and injury, low social support, and a history of mental health disorders predicted adjustment disorders. Most of these predictors differentiated individuals with adjustment disorders from individuals with no mental health disorders. Participants with adjustment disorders were more likely to have experienced accidents than were those with posttraumatic stress disorder but were less likely to have experienced assaults and abuse, neglect, and maltreatment. More research is needed to identify factors that differentiate adjustment disorders from other mental health disorders.
Because very few studies adjusted for confounders (e.g., demographic variables, mental health histories, and a variety of stressors), it was not possible to identify independent associations between predictors and adjustment disorders.
We identified a number of factors that predicted adjustment disorders compared to no mental health diagnosis. The majority of studies were rated as moderate or high in risk of bias, suggesting that more rigorous research is needed to confirm the relationships we detected.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Systemic bacterial infection is characterized by a robust whole-organism inflammatory response. Analysis of the immune response to infection involves technologies that typically focus on single organ ...systems and lack spatial information. Additionally, the analysis of individual inflammatory proteins requires antibodies specific to the protein of interest, limiting the panel of proteins that can be analyzed. Herein we describe the application of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) to mice systemically infected with Staphylococcus aureus to identify inflammatory protein masses that respond to infection throughout an entire infected animal. Integrating the resolution afforded by magnetic resonance imaging (MRI) with the sensitivity of MALDI IMS provides three-dimensional spatially resolved information regarding the distribution of innate immune proteins during systemic infection, allowing comparisons to in vivo structural information and soft-tissue contrast via MRI. Thus, integrating MALDI IMS with MRI provides a systems-biology approach to study inflammation during infection.
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► IMS provides a whole-animal view of the inflammatory response to infection ► IMS identifies protein masses that are abundant at sites of inflammation ► Anatomic information at the site of infection can be generated by MRI ► Integrated IMS and MRI enable a 3D view of the host-pathogen interaction
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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