The high-resolution and mass accuracy of Fourier transform mass spectrometry (FT-MS) has made it an increasingly popular technique for discerning the composition of soil, plant and aquatic samples ...containing complex mixtures of proteins, carbohydrates, lipids, lignins, hydrocarbons, phytochemicals and other compounds. Thus, there is a growing demand for informatics tools to analyze FT-MS data that will aid investigators seeking to understand the availability of carbon compounds to biotic and abiotic oxidation and to compare fundamental chemical properties of complex samples across groups. We present ftmsRanalysis, an R package which provides an extensive collection of data formatting and processing, filtering, visualization, and sample and group comparison functionalities. The package provides a suite of plotting methods and enables expedient, flexible and interactive visualization of complex datasets through functions which link to a powerful and interactive visualization user interface, Trelliscope. Example analysis using FT-MS data from a soil microbiology study demonstrates the core functionality of the package and highlights the capabilities for producing interactive visualizations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective:Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but many patients do not respond. Brain functions governing treatment outcome are not well ...characterized. The authors examined brain systems relevant to emotional reactivity and regulation, constructs that are thought to be central to PTSD and exposure therapy effects, to identify the functional traits of individuals most likely to benefit from treatment.Method:Individuals with PTSD underwent functional MRI (fMRI) while completing three tasks assessing emotional reactivity and regulation. Participants were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30). A random subset of the prolonged exposure group (N=17) underwent single-pulse transcranial magnetic stimulation (TMS) concurrent with fMRI to examine whether predictive activation patterns reflect causal influence within circuits. Linear mixed-effects modeling in line with the intent-to-treat principle was used to examine how baseline brain function moderated the effect of treatment on PTSD symptoms.Results:At baseline, individuals with larger treatment-related symptom reductions (compared with the waiting list condition) demonstrated 1) greater dorsal prefrontal activation and 2) less left amygdala activation, both during emotion reactivity; 3) better inhibition of the left amygdala induced by single TMS pulses to the right dorsolateral prefrontal cortex; and 4) greater ventromedial prefrontal/ventral striatal activation during emotional conflict regulation. Reappraisal-related activation was not a significant moderator of the treatment effect.Conclusions:Capacity to benefit from prolonged exposure in PTSD is gated by the degree to which prefrontal resources are spontaneously engaged when superficially processing threat and adaptively mitigating emotional interference, but not when deliberately reducing negative emotionality.
AbstractIntroductionStreptococcus pneumoniae is a leading cause of bacteremia, bacterial pneumonia, and meningitis, and is associated with substantial morbidity and mortality, particularly in those ...under 2 years of age and those over 65 years of age. While significant progress against S. pneumoniae-related disease has been made as a result of the introduction of pneumococcal conjugate vaccines (PCV7, PCV10 and PCV13), there remains value in further expanding pneumococcal vaccine serotype coverage. Here we present the first report of a 20-valent pneumococcal conjugate vaccine (PCV20) containing capsular polysaccharide conjugates present in PCV13 as well as 7 new serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) which are important contributors to pneumococcal disease. MethodsThis Phase I first-in-human study was a randomized, controlled, observer-blinded study with a two-arm parallel design to assess the safety, tolerability, and immunogenicity of PCV20 in adults. A total of 66 healthy adults 18–49 years of age with no history of pneumococcal vaccination were enrolled and randomized to receive a single dose of PCV20 or a licensed tetanus, diphtheria, acellular pertussis combination vaccine (Tdap) control. Local injection site reactions, select systemic symptoms, laboratory studies, and adverse events were assessed. Opsonophagocytic activity (OPA) titers and IgG concentrations were measured in sera collected prior to, and approximately one month (28–35 days) after vaccination. ResultsVaccination with PCV20 elicited substantial IgG and functional bactericidal immune responses as demonstrated by increases in IgG geometric mean concentrations (GMCs) and OPA geometric mean titers (GMTs) to the 20 vaccine serotypes. The overall safety profile of PCV20 was similar to Tdap, and generally consistent with that observed after PCV13 administration. ConclusionsVaccination with PCV20 was well tolerated and induced substantial functional (OPA) and IgG responses to all vaccine serotypes. There were no safety issues identified in this Phase 1 study, and the data supported further evaluation of PCV20.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Soil organic matter (SOM) dynamics are central to soil biogeochemistry and fertility. The retention of SOM is governed initially by interactions with minerals, which mediate the sorption of ...chemically diverse organic matter (OM) molecules via distinct surface areas and chemical functional group availabilities. Unifying principles of mineral-OM interactions remain elusive because of the multi-layered nature of biochemical-mineral interactions that contribute to soil aggregate formation and the heterogeneous nature of soils among ecosystems. This study sought to understand how soil mineralogy as well as nitrogen (N) enrichment regulate OM composition in grassland soils. Using a multi-site grassland experiment, we demonstrate that the composition of mineral-associated OM depended on the clay content and specific mineral composition in soils across the sites. With increasing abundance of ferrihydrite (Fh) across six different grassland locations, OM in the hydrophobic zone became more enriched in lipid- and protein-like compounds, whereas the kinetic zone OM became more enriched in lignin-like molecules. These relationships suggest that the persistence of various classes of OM in soils may depend on soil iron mineralogy and provide experimental evidence to support conceptual models of zonal mineral-OM associations. Experimental N addition disrupted the accumulation of protein-like molecules in the hydrophobic zone and the positive correlation of lignin-like molecules in the kinetic zone with Fh content, compared to unfertilized soils. These data suggest that mineralogy and clay content together influence the chemical composition not only of mineral-associated OM, but also of soluble compounds within the soil matrix. If these relationships are prevalent over larger spatial and temporal scales, they provide a foundation for understanding SOM cycling and persistence under a variety of environmental contexts.
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•Beyond clay content, mineralogy strongly controlled the composition of MAOM.•Ferrihydrite accumulated proteins and lipids in the hydrophobic zone of MAOM.•The mineral core influenced biochemical persistence of OM in the kinetic zone.•Nitrogen fertilization altered carbon chemistry and organo-mineral interactions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pediatric pneumomediastinum: Symptom-based management Dougherty, Danielle; Meyer, Kayla M.; Thompson, Allison R. ...
Journal of pediatric surgery,
March 2023, 2023-Mar, 2023-03-00, Volume:
58, Issue:
3
Journal Article
Peer reviewed
•Despite the known benign course of pediatric spontaneous pneumomediastinum, there is no consensus on workup and management.•Patients with similar presentations undergo a variety of imaging ...studies.•Presenting symptoms should be the main determinant of evaluation and management.•There is an opportunity to decrease unnecessary radiation exposure in this patient population.
Pediatric spontaneous pneumomediastinum is known to have a benign course. Despite this, there is no consensus or standardization for the workup and management. There are often a variety of imaging studies performed for patients with similar presentations.
This is a retrospective chart review evaluating the presentation, workup, and management of all pediatric patients with a primary diagnosis of spontaneous pneumomediastinum over a 5-year period at a children's hospital.
Of the 62 patients, the initial workup consisted of either a chest x-ray (CXR) only (n = 31, 50%), a chest computed tomography scan only (n = 11, 18%) or both (n = 14, 23%); additionally, some patients came with ‘other’ imaging only (n = 3, 5%) or no imaging (n = 3, 5%). Twenty-seven patients (44%) underwent an additional CXR and 19 (31%) underwent an esophagram. All esophagrams were negative for an esophageal leak. A presenting symptom of pain was associated with a hospital stay of less than 24 h (p = 0.008) while shortness of breath (p = 0.0005) and emesis (p = 0.0006) were associated with a hospital stay of greater than 24 h. Associated diagnoses of respiratory infections (p = 0.02) and gastrointestinal issues (p = 0.006), such as hyperemesis, were associated with inpatient admission.
Pediatric patients with spontaneous pneumomediastinum benefit from evaluation, management, and treatment based on their presenting symptoms. There is an opportunity to decrease unnecessary radiation exposure in this patient population with fewer CXRs and avoidance of esophagrams, neither of which alter management.
Level III.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Autophagy is an important mechanism for nonselective intracellular breakdown whereby cytosol and organelles are encapsulated in vesicles, which are then engulfed and digested by lytic ...vacuoles/lysosomes. In yeast, this encapsulation employs a set of autophagy (ATG) proteins that direct the conjugation of two ubiquitin-like protein tags, ATG8 and ATG12, to phosphatidylethanolamine and the ATG5 protein, respectively. Using an Arabidopsis (Arabidopsis thaliana) atg7 mutant unable to ligate either tag, we previously showed that the ATG8/12 conjugation system is important for survival under nitrogen-limiting growth conditions. By reverse-genetic analyses of the single Arabidopsis gene encoding ATG5, we show here that the subpathway that forms the ATG12-ATG5 conjugate also has an essential role in plant nutrient recycling. Similar to plants missing ATG7, those missing ATG5 display early senescence and are hypersensitive to either nitrogen or carbon starvation, which is accompanied by a more rapid loss of organellar and cytoplasmic proteins. Multiple ATG8 isoforms could be detected immunologically in seedling extracts. Their abundance was substantially elevated in both the atg5 and atg7 mutants, caused in part by an increase in abundance of several ATG8 mRNAs. Using a green fluorescent protein-ATG8a fusion in combination with concanamycin A, we also detected the accumulation of autophagic bodies inside the vacuole. This accumulation was substantially enhanced by starvation but blocked in the atg7 background. The use of this fusion in conjunction with atg mutants now provides an important marker to track autophagic vesicles in planta.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Objective:Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but a comprehensive, emotion-focused perspective on how psychotherapy affects brain function is lacking. ...The authors assessed changes in brain function after prolonged exposure therapy across three emotional reactivity and regulation paradigms.Method:Individuals with PTSD underwent functional MRI (fMRI) at rest and while completing three tasks assessing emotional reactivity and regulation. Individuals were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30) and underwent a second scan approximately 4 weeks after the last treatment session or a comparable waiting period, respectively.Results:Treatment-specific changes were observed only during cognitive reappraisal of negative images. Psychotherapy increased lateral frontopolar cortex activity and connectivity with the ventromedial prefrontal cortex/ventral striatum. Greater increases in frontopolar activation were associated with improvement in hyperarousal symptoms and psychological well-being. The frontopolar cortex also displayed a greater variety of temporal resting-state signal pattern changes after treatment. Concurrent transcranial magnetic stimulation and fMRI in healthy participants demonstrated that the lateral frontopolar cortex exerts downstream influence on the ventromedial prefrontal cortex/ventral striatum.Conclusions:Changes in frontopolar function during deliberate regulation of negative affect is one key mechanism of adaptive psychotherapeutic change in PTSD. Given that frontopolar connectivity with ventromedial regions during emotion regulation is enhanced by psychotherapy and that the frontopolar cortex exerts downstream influence on ventromedial regions in healthy individuals, these findings inform a novel conceptualization of how psychotherapy works, and they identify a promising target for stimulation-based therapeutics.
While Enhanced Recovery After Surgery (ERAS) protocols are becoming more common in pediatric surgery, there is still little published about protocol compliance and sustainability.
This is a ...prospective observational study to evaluate the compliance of an ERAS protocol for pectus repair at a large academic children’s hospital. Our primary outcome was overall protocol compliance at 1-y postimplementation of the ERAS protocol. Our comparison group included all pectus repairs for 2 y before protocol implementation.
Overall protocol compliance at 12 mo was 89%. Of the 16 pectus repairs included in the ERAS protocol group, 94% (n = 15) and 94% (n = 15) received preoperative acetaminophen and gabapentin, respectively, which was significantly greater than the historical control group (P < 0.001). For the intraoperative components analyzed, only the intrathecal morphine was significantly different than historical controls (100% versus 49%, P < 0.001). Postoperatively, the time from operating room to return to normal diet was shorter for the ERAS group (0.53 d versus 1.16 d, P < 0.001). There was no significant difference in readmission rates between the two groups.
ERAS protocol compliance varies based on phase of care. Solutions to sustain protocols depend on the institution and the patient population. However, the utilization of implementation science fundamentals was invaluable in this study to identify and address areas for improvement in protocol compliance. Other institutions may adapt these strategies to improve protocol compliance at their centers.
•Implementation of ERAS protocols has been shown to improve clinical outcomes.•ERAS protocol compliance and sustainability can be improved using fundamentals of implementation science. Methods that can be broadly applied in pediatric surgery are highlighted in this article.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The microbial and molecular characterization of the ectorhizosphere is an important step towards developing a more complete understanding of how the cultivation of biofuel crops can be undertaken in ...nutrient poor environments. The ectorhizosphere of Setaria is of particular interest because the plant component of this plant-microbe system is an important agricultural grain crop and a model for biofuel grasses. Importantly, Setaria lends itself to high throughput molecular studies. As such, we have identified important intra- and interspecific microbial and molecular differences in the ectorhizospheres of three geographically distant Setaria italica accessions and their wild ancestor S. viridis. All were grown in a nutrient-poor soil with and without nutrient addition. To assess the contrasting impact of nutrient deficiency observed for two S. italica accessions, we quantitatively evaluated differences in soil organic matter, microbial community, and metabolite profiles. Together, these measurements suggest that rhizosphere priming differs with Setaria accession, which comes from alterations in microbial community abundances, specifically Actinobacteria and Proteobacteria populations. When globally comparing the metabolomic response of Setaria to nutrient addition, plants produced distinctly different metabolic profiles in the leaves and roots. With nutrient addition, increases of nitrogen containing metabolites were significantly higher in plant leaves and roots along with significant increases in tyrosine derived alkaloids, serotonin, and synephrine. Glycerol was also found to be significantly increased in the leaves as well as the ectorhizosphere. These differences provide insight into how C4 grasses adapt to changing nutrient availability in soils or with contrasting fertilization schemas. Gained knowledge could then be utilized in plant enhancement and bioengineering efforts to produce plants with superior traits when grown in nutrient poor soils.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Surgical repair of pectus excavatum and carinatum in children has historically been associated with severe postoperative pain and prolonged hospitalization. Enhanced Recovery After Surgery (ERAS) is ...a multidisciplinary, multimodal approach designed to fast-track surgical care. However, obstacles to implementation have led to very few within pediatric surgery. The aim of this study is to outline the process of development and implementation of an ERAS protocol for pectus surgical repair using fundamental principles of implementation science.
A multidisciplinary team of providers worked collaboratively to develop an ERAS protocol for surgical repair of pectus excavatum and carinatum and methods for identifying eligible patients. The surgical champion collaborated with all end users to review and revise the ERAS protocol, assessing all foreseeable barriers and facilitators prior to implementation.
Our entire pediatric surgery team, nurses at every stage (clinic/preoperative/recovery/floor), physical therapy, and information technology contributed to the creation and implementation of an ERAS protocol with seven phases of care. The finalized version was implemented by end users focusing on four main areas: pain control, ambulation, diet, and education. Barriers and facilitators were continually addressed with an iterative process to improve the success of implementation.
This is one of the first studies in children which details the step-by-step process of developing and implementing an ERAS protocol for pectus excavatum and carinatum. The process of development and implementation of an ERAS protocol as outlined in this manuscript can serve as a model for future ERAS protocols in pediatric surgery.
•Identify champions and team of multidisciplinary stakeholders early in the process.•Engage stakeholders early and regularly in protocol development and implementation.•Identify barriers and facilitators to implementation.•Implementation science benefits: common language, address barriers, and track progress.•Use an iterative process to encourage and improve protocol implementation.
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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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