Publications by authors named "Sarah Johnson"

547 Publications

Influence of Calcium Perchlorate on the Search for Martian Organic Compounds with MTBSTFA/DMF Derivatization.

Astrobiology 2021 Sep;21(9):1137-1156

Space Science Exploration Division (Code 690), NASA Goddard Space Flight Center, Greenbelt, Maryland, USA.

-butyldimethylsilyl--methyltrifluoroacetamide (MTBSTFA), mixed with the solvent -dimethylformamide (DMF), is used as a derivatizing reagent by the Sample Analysis at Mars (SAM) experiment onboard NASA's Curiosity rover and will soon be utilized by the Mars Organic Molecule Analyzer experiment onboard the ESA/Roscosmos Rosalind Franklin rover. The pyrolysis products of MTBSTFA, DMF, and the MTBSTFA/DMF mixtures, obtained at different temperatures, were analyzed. Two different pyrolysis modes were studied, flash pyrolysis and ramp pyrolysis (35°C/min), to evaluate the potential influence of the sample heating speed on the production of products in space chromatographs. The effect of the presence of calcium perchlorate on the pyrolysis products of MTBSTFA/DMF was also studied to ascertain the potential effect of perchlorate species known to be present at the martian surface. The results show that MTBSTFA/DMF derivatization should be applied below 300°C when using flash pyrolysis, as numerous products of MTBSTFA/DMF were formed at high pyrolysis temperatures. However, when an SAM-like ramp pyrolysis was applied, the final pyrolysis temperature did not appear to influence the degradation products of MTBSTFA/DMF. All products of MTBSTFA/DMF pyrolysis are listed in this article, providing a major database of products for the analysis of martian analog samples, meteorites, and the analysis of martian rocks and soils. In addition, the presence of calcium perchlorate does not show any obvious effects on the pyrolysis of MTBSTFA/DMF: Only chloromethane and TBDMS-Cl (chloro-tertbutyldimethylsilane) were detected, whereas chlorobenzene and other chlorine-bearing compounds were not detected. However, other chlorine-bearing compounds were detected after pyrolysis of the Murchison meteorite in the presence of calcium perchlorate. This result reinforces previous suggestions that chloride-bearing compounds could be reaction products of martian samples and perchlorate.
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http://dx.doi.org/10.1089/ast.2020.2393DOI Listing
September 2021

Functional trait data for vascular plant species from northeastern North America.

Ecology 2021 Sep 1:e03527. Epub 2021 Sep 1.

Department of Botany, University of Wisconsin-Madison, 430 Lincoln Drive, Madison, WI, 53706, USA.

Wisconsin's plant communities are responding to shifting disturbance regimes, habitat fragmentation, aerial nitrogen deposition, exotic species invasions, ungulate herbivory, and successional processes. To better understand how plant functional traits mediate species' responses to changing environmental conditions, we collected a large set of functional trait data for vascular plant species occupying Wisconsin forests and grasslands. We used standard protocols to make 76,213 measurements of 34 quantitative traits. These data provide rich information on genome size, physical leaf traits (length, width, circularity, thickness, dry matter content, specific leaf area, etc.), chemical leaf traits (carbon, nitrogen, phosphorus, potassium, calcium, magnesium, ash), life history traits (vegetative and flower heights, seed mass), and traits affecting plant palatability (leaf fiber, fat, and lignin). These trait values derive from replicate measurements on 12+ individuals of each species from multiple sites and 45+ individuals for a selected subset of species. Measurements typically reflect values for individuals though some chemical traits involved composite samples from several individuals at the same site. We also qualitatively characterize each species by plant family, woodiness, functional group, and Raunkiaer lifeform. These data allow us to characterize trait dimensionality, differentiation, and covariation among temperate plant species (e.g., leaf and stem economic syndromes). We can also characterize species' responses to environmental gradients and drivers of ecological change. With survey and resurvey data available from >400 sites in Wisconsin, we can analyze variation in community trait distributions and diversity over time and space. These data thus allow us to assess how trait divergence vs. convergence affect community assembly and how traits may be related to half-century shifts in the distribution and abundance of these species. The data set can be used for non-commercial purposes. The data set is licensed as follows: CC-By Attribution 4.0 International. We request users cite both the OSF data set and this Ecology data paper publication.
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http://dx.doi.org/10.1002/ecy.3527DOI Listing
September 2021

Impact of HLA type, age and chronic viral infection on peripheral T-cell receptor sharing between unrelated individuals.

PLoS One 2021 30;16(8):e0249484. Epub 2021 Aug 30.

Adaptive Biotechnologies, Seattle, Washington, United States of America.

The human adaptive immune system must generate extraordinary diversity to be able to respond to all possible pathogens. The T-cell repertoire derives this high diversity through somatic recombination of the T-cell receptor (TCR) locus, a random process that results in repertoires that are largely private to each individual. However, factors such as thymic selection and T-cell proliferation upon antigen exposure can affect TCR sharing among individuals. By immunosequencing the TCRβ variable region of 426 healthy individuals, we find that, on average, fewer than 1% of TCRβ clones are shared between individuals, consistent with largely private TCRβ repertoires. However, we detect a significant correlation between increased HLA allele sharing and increased number of shared TCRβ clones, with each additional shared HLA allele contributing to an increase in ~0.01% of the total shared TCRβ clones, supporting a key role for HLA type in shaping the immune repertoire. Surprisingly, we find that shared antigen exposure to CMV leads to fewer shared TCRβ clones, even after controlling for HLA, indicative of a largely private response to major viral antigenic exposure. Consistent with this hypothesis, we find that increased age is correlated with decreased overall TCRβ clone sharing, indicating that the pattern of private TCRβ clonal expansion is a general feature of the T-cell response to other infectious antigens as well. However, increased age also correlates with increased sharing among the lowest frequency clones, consistent with decreased repertoire diversity in older individuals. Together, all of these factors contribute to shaping the TCRβ repertoire, and understanding their interplay has important implications for the use of T cells for therapeutics and diagnostics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249484PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405014PMC
August 2021

Assessing Challenges with Access to Care for Patients Presenting to the Emergency Department for Non-Emergent Complaints.

Med J (Ft Sam Houst Tex) 2021 Jul-Sep(PB 8-21-07/08/09):74-80

US Army Institute of Surgical Research, JBSA Ft. Sam Houston, TX; Brooke Army Medical Center, JBSA Ft. Sam Houston, TX; and Uniformed Services University of the Health Science, Bethesda, MD.

Introduction: Emergency department (ED) utilization continues to climb nationwide resulting in overcrowding, increasing wait times, and a surge in patients with non-urgent conditions. Patients frequently choose the ED for apparent non-emergent medical issues or injuries that after-the-fact could be cared for in a primary care setting. We seek to better understand the reasons why patients choose the ED over their primary care managers.

Methods: We prospectively surveyed patients that signed into the ED at the Brooke Army Medical Center as an emergency severity index of 4 or 5 (non-emergent triage) regarding their visit. We then linked their survey data to their ED visit including interventions, diagnoses, diagnostics, and disposition by using their electronic medical record. We defined their visit to be non-urgent and more appropriate for primary care, or primary care eligible, if they were discharged home and received no computed tomography (CT) imaging, ultrasound, magnetic resonance imaging (MRI), intravenous (IV) medications, or intramuscular (IM) controlled substances.

Results: During the 2-month period, we collected data on 208 participants out of a total of 252 people offered a survey (82.5%). There were 92% (n=191) that were primary care eligible within our respondent pool. Most reported very good (38%) or excellent (21%) health at baseline. On survey assessing why they came, inability to get a timely appointment (n=73), and a self-reported emergency (n=58) were the most common reported reasons. Most would have utilized primary care if they had a next-morning appointment available (n=86), but many reported they would have utilized the ED regardless of primary care availability (n=77). The most common suggestion for improving access to care was more primary care appointment availability (n=96). X-rays were the most frequent study (37%) followed by laboratory studies (20%). Before coming to the ED, 38% (n=78) reported trying to contact their primary care for an appointment. Before coming to the ED, 22% (n=46) reported contacting the nurse advice line. Based on our predefined model, 92% (n=191) of our respondents were primary care eligible within our respondent pool.

Conclusions: Patient perceptions of difficulty obtaining appointments appear to be a major component of the ED use for non-emergent visits. Within our dataset, most patients surveyed stated they had difficulty obtaining a timely appointment or self-reported as an emergency. Data suggests most patients surveyed could be managed in the primary care setting.
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August 2021

Plasma cells expression from smouldering myeloma to myeloma reveals the importance of the PRC2 complex, cell cycle progression, and the divergent evolutionary pathways within the different molecular subgroups.

Leukemia 2021 Aug 7. Epub 2021 Aug 7.

Melvin and Bren Simon Comprehensive Cancer Center, Division of Hematology Oncology, Indiana University, Indianapolis, IN, USA.

Sequencing studies have shed some light on the pathogenesis of progression from smouldering multiple myeloma (SMM) and symptomatic multiple myeloma (MM). Given the scarcity of smouldering samples, little data are available to determine which translational programmes are dysregulated and whether the mechanisms of progression are uniform across the main molecular subgroups. In this work, we investigated 223 SMM and 1348 MM samples from the University of Arkansas for Medical Sciences (UAMS) for which we had gene expression profiling (GEP). Patients were analysed by TC-7 subgroup for gene expression changes between SMM and MM. Among the commonly dysregulated genes in each subgroup, PHF19 and EZH2 highlight the importance of the PRC2.1 complex. We show that subgroup specific differences exist even at the SMM stage of disease with different biological features driving progression within each TC molecular subgroup. These data suggest that MMSET SMM has already transformed, but that the other precursor diseases are distinct clinical entities from their symptomatic counterpart.
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http://dx.doi.org/10.1038/s41375-021-01379-yDOI Listing
August 2021

Library Patrons' Psychosocial Needs: Perceptions of Need and Reasons for Accessing Social Work Services.

Soc Work 2021 Aug 1. Epub 2021 Aug 1.

Public libraries in the United States have begun to partner with social work to address the psychosocial needs observed in patrons that are beyond the training and education of most library staff. This is a new area of inquiry with limited research available. Of the few published studies, the majority focus on staff perceptions of patrons' needs and surveys of patrons experiencing homelessness about their use of public libraries. The present study is the first to examine and compare staff perception of patrons' needs, patrons' self-expressed needs, and the actual use of social work services by patrons within one library system. Comparisons are explored between actual service usage alongside the perception of patrons' needs as originally reported by both staff and patron groups. Implications for library-based social work practice are discussed.
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http://dx.doi.org/10.1093/sw/swab032DOI Listing
August 2021

Predicting probable eating disorder case-status in men using the Clinical Impairment Assessment: Evidence for a gender-specific threshold.

Eat Behav 2021 08 20;42:101541. Epub 2021 Jul 20.

Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.

The Clinical Impairment Assessment (CIA) is a widely used self-report measure of the psychosocial impairment associated with eating-disorder symptoms. Past studies recommended a global CIA score of 16 to identify clinically significant impairment associated with a probable eating disorder (ED). However, to date, research on the properties of the CIA has been conducted in majority-women samples. Preliminary research on gender differences in CIA scores suggested men with EDs report less impairment on the CIA relative to women with EDs. Thus, the purpose of this study was to test if a different impairment threshold is needed to identify cases of men with EDs. We hypothesized that a lower CIA threshold, relative to that identified in majority-women samples, would most accurately identify men with EDs. Participants (N = 162) were men from our university-based and general community-based ED participant registry who completed the CIA and Eating Disorder Diagnostic Scale. Both precision-recall and receiver operating characteristic curves assessed what CIA global score threshold most accurately identified men with EDs. Both analytic approaches indicated that a CIA global score of 13 best predicted ED case-status in men. Consistent with past research, men with a clinically significant ED appear to report lower impairment on the CIA. Results have implications for screening and assessing for substantial ED-related impairment in men. Additionally, past research using the CIA to identify men with EDs may have under-identified men with clinically significant symptoms.
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http://dx.doi.org/10.1016/j.eatbeh.2021.101541DOI Listing
August 2021

How It Started, and How It's Going: Global Family Planning Programs.

Clin Obstet Gynecol 2021 09;64(3):422-434

PSI.

Family planning (FP) is the domain that enables people to have their desired number of children if any, and the desired spacing of births. FP initiatives are cross-cutting approaches to empower people with human and reproductive rights, lessen child morbidity and pregnancy-related morbidity and mortality, alleviate poverty, slow climate change, provide sustainable economic growth and development, advance education, and voluntarily slow overpopulation. We examine global FP programs: the history, drivers, and indicators to measure impact, policy, and strategy that surrounds human reproduction. We focus on current trends of task-sharing, self-care, digital health solutions, and the ever-changing contexts with our current pandemic of coronavirus disease 2019.
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http://dx.doi.org/10.1097/GRF.0000000000000625DOI Listing
September 2021

An empirical evaluation of the diagnostic threshold between full-threshold and sub-threshold bulimia nervosa.

Eat Behav 2021 08 13;42:101540. Epub 2021 Jul 13.

University of Kansas, United States of America.

Previous research has failed to find differences in eating disorder and general psychopathology and impairment between people with sub- and full-threshold bulimia nervosa (BN). The purpose of the current study was to test the validity of the distinction between sub- and full-threshold BN and to determine the frequency of objective binge episodes and inappropriate compensatory behaviors that would best distinguish between sub- and full-BN. Community-recruited adults (83.5% female) with current sub-threshold (n = 105) or full-threshold BN (n = 99) completed assessments of eating-disorder psychopathology, clinical impairment, internalizing problems, and drug and alcohol misuse. Receiver operating characteristic curve analysis was used to evaluate whether eating-disorder psychopathology, clinical impairment, internalizing problems, and drug and alcohol misuse could empirically discriminate between sub- and full-threshold BN. The frequency of binge episodes and inappropriate compensatory behaviors (AUC = 0.94) was "highly accurate" in discriminating between sub- and full-threshold BN; however, only objective binge episodes was a significant predictor of BN status. Internalizing symptoms (AUC = 0.71) were "moderately accurate" at distinguishing between sub- and full-BN. Neither clinical impairment (AUC = 0.60) nor drug (AUC = 0.56) or alcohol misuse (AUC = 0.52) discriminated between groups. Results suggested that 11 episodes of binge eating and 17 episodes of inappropriate compensatory behaviors optimally distinguished between sub- and full-BN. Overall, results provided mixed support for the distinction between sub- and full-threshold BN. Future research to clarify the most meaningful way to discriminate between sub- and full-threshold is warranted to improve the criterion-related validity of the diagnostic system.
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http://dx.doi.org/10.1016/j.eatbeh.2021.101540DOI Listing
August 2021

Transplantation of an obesity-associated human gut microbiota to mice induces vascular dysfunction and glucose intolerance.

Gut Microbes 2021 Jan-Dec;13(1):1940791

Department of Food Science & Human Nutrition, Colorado State University, Fort Collins, CO, USA.

Recent preclinical data suggest that alterations in the gut microbiota may be an important factor linking obesity to vascular dysfunction, an early sign of cardiovascular disease. The purpose of this study was to begin translation of these preclinical data by examining whether vascular phenotypes in humans are transmissible through the gut microbiota. We hypothesized that germ-free mice colonized with gut microbiota from obese individuals would display diminished vascular function compared to germ-free mice receiving microbiota from lean individuals.We transplanted fecal material from obese and lean age-and sex-matched participants with disparate vascular function to germ-free mice. Using Principle Component Analysis, the microbiota of colonized mice separated by donor group along the first principle component, accounting for between 70-93% of the total variability in the dataset. The microbiota of mice receiving transplants from lean individuals was also characterized by increased alpha diversity, as well as increased relative abundance of potentially beneficial bacteria, including , and . Endothelium-dependent dilation, aortic pulse wave velocity and glucose tolerance were significantly altered in mice receiving microbiota from the obese donor relative to those receiving microbiota from the lean donor or those remaining germ-free.These data indicate that the obesity-associated human gut microbiota is sufficient to alter the vascular phenotype in germ-free mice in the absence of differences in body weight or dietary manipulation, and provide justification for future clinical trials to test the efficacy of microbiota-targeted therapies in the prevention or treatment of cardiovascular disease.
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http://dx.doi.org/10.1080/19490976.2021.1940791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317959PMC
July 2021

Indexing cerebrovascular health using near-infrared spectroscopy.

Sci Rep 2021 Jul 20;11(1):14812. Epub 2021 Jul 20.

School of Engineering, University of Newcastle, Callaghan, Australia.

Near-infrared spectroscopy (NiRS) is a relatively new technology of brain imaging with its potential in the assessment of cerebrovascular health only recently discovered. Encouraging early results suggest that NiRS can be used as an inexpensive and portable cerebrovascular health tracking device using a recently proposed pulse relaxation function (PReFx). In this paper, we propose a new NiRS timing index, [Formula: see text], of cerebrovascular health. [Formula: see text] is a novel use of the NiRS technology. [Formula: see text] is motivated by the previously proved relationship of the timing of the reflected wave with vascular resistance and compliance in the context of pressure waveforms. We correlated both [Formula: see text] and PReFx against age, a non-exercise cardiorespiratory fitness (CRF) index, and two existing indices of cerebrovascular health, namely transcranial Doppler (TCD) augmentation index, [Formula: see text], and magnetic resonance imaging (MRI) blood flow pulsatility index, [Formula: see text]. The [Formula: see text] correlations with Age, CRF, [Formula: see text] and [Formula: see text] all are significant, i.e., [Formula: see text] ([Formula: see text]), [Formula: see text] ([Formula: see text]), [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]), respectively. PReFx, however, did not have significant correlations with any of the vascular health factors. The proposed timing index is a reliable indicator of cerebrovascular aging factors in the NiRS waveform.
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http://dx.doi.org/10.1038/s41598-021-94348-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292377PMC
July 2021

Characterization of standard work tools for intrathecal baclofen therapy.

Childs Nerv Syst 2021 Jul 14. Epub 2021 Jul 14.

Department of Neurological Surgery, Division of Pediatric Neurosurgery, Riley Hospital for Children, Indiana University School of Medicine, 705 Riley Hospital Drive, Rm #1601C, Indianapolis, IN, 46202, USA.

Purpose: Intrathecal baclofen (ITB) has been an effective therapy since the 1980s, with widely reported revision, infection, and complication rates. Publications targeting surgical workflow have resulted in decreased infection and revision rates, but a standard workflow for the entire pathway has not been described. To present, define, and test standard work tools for patients receiving ITB to promote uniformity and standard of care in the field.

Methods: A multidisciplinary approach from the movement disorder program of a tertiary care center defined all steps comprising the ITB pathway, and then developed standard work tools to decrease variability with respect to preoperative workup, day of surgery protocol, post-operative care, and also evaluation and treatment with respect to pump infection or malfunction.

Results: Defined steps used at specific points of ITB pathway are presented with a single institution's outcome using the protocol from July 2017 to November 2020. A total of 60 procedures were performed. The overall complication rate was 14.5% at 6 months. Complications included an infection rate of 3.6% at 6 months, wound revision rate of 1.8% at 6 months, CSF leak rate of 1.7% at 6 months, and a 30-day readmission rate related to initial surgery of 6.7%.

Conclusions: Workflow efficiency and optimization for ITB patients can be used to obtain lower complication rates compared to historical cohorts in literature. A single-center, retrospective review highlights this.
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http://dx.doi.org/10.1007/s00381-021-05290-wDOI Listing
July 2021

An Analysis of Prehospital Blood Administration in the Indo-Pacific Command.

Med J (Ft Sam Houst Tex) 2021 Apr-Jun(PB 8-21-04/05/06):66-71

US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX, Brooke Army Medical Center, JBSA Fort Sam Houston, TX, and Uniformed Services University of the Health Sciences, Bethesda, MD.

Background: Blood products are often a life-saving intervention for both traumatic and medical indications. The United States Indo-Pacific Command (INDOPACOM) is the largest Geographic Combat Command (GCC). Procurement of blood products that meet the US military healthcare standards throughout this region is challenging. Yet, the frequency to which this life-saving intervention is administered remains unclear. We seek to describe blood product administration throughout INDOPACOM.

Methods: This is a secondary analysis of a previously described dataset from the US Transportation Command (TRANSCOM) Regulating Command and Control and Evacuation System (TRAC2ES) from 2008 to 2018.

Results: Between 2008 and 2018, there were 4,217 cases in TRAC2ES originating within INDOPACOM, of which 173 (4%) cases involved blood product transfusion. The largest percentage for patients receiving a blood transfusion was 19-29 years old (29%), followed by patients under a year (21%). Most (66%) of the patients classified as male. Almost half of the patients (49%) were dependents of members of service in parallel with the young patient ages. Anemia (23%) and trauma (20%) , mostly non-combat related, were the largest proportions of indications. The common blood product used was packed red cells (72%) followed by fresh frozen plasma (16%).

Conclusions: Blood products were administered to nearly 1 out of every 25 patients transported within INDOPACOM, which highlights the need for reliable methods for obtaining and maintaining blood products. Given INDOPACOM's vast area of responsibility and possibility for a peer-to-peer war, finding optimal methods to transport and store blood and blood products is imperative.
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July 2021

Measurement invariance of the Eating Pathology Symptoms Inventory (EPSI) in adolescents and adults.

Eat Behav 2021 08 2;42:101538. Epub 2021 Jul 2.

Recovery Record, Inc., San Francisco, CA, USA.

Adolescence is a common period for eating disorder (ED) onset. The availability of psychometrically sound measures of ED psychopathology enables clinicians to accurately assess symptoms and monitor treatment outcomes continuously from adolescence and adulthood. The purpose of this study was to assess if the Eating Pathology Symptoms Inventory (EPSI) is invariant across adolescents and adults. Participants (N = 29,821) were adolescent (n = 5250) and adult (n = 24,571) users of the Recovery Record (RR) mobile phone application who provided EPSI responses through the application. Measurement invariance testing was conducted to assess invariance of the EPSI Body Dissatisfaction, Restricting, Excessive Exercise, Purging, Cognitive Restraint, and Binge Eating scales across adolescents (age 13 through 17) and adults (age 18 and older). Findings indicated that all EPSI factors administered in the RR app replicated in both adolescent and adult users. The EPSI factor structure was largely equivalent in adolescents and adults, demonstrating evidence for configural and metric invariance, as well as some evidence for scalar invariance. Our results indicated that EPSI scales measured the same constructs across development. Clinicians and researchers may benefit from utilizing the EPSI to measure ED psychopathology in adolescents and for continued progress monitoring into adulthood.
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http://dx.doi.org/10.1016/j.eatbeh.2021.101538DOI Listing
August 2021

"We can work it out": positive problem solving as a mediator between perspective-taking and relationship satisfaction among college students.

J Am Coll Health 2021 Jul 9:1-14. Epub 2021 Jul 9.

Psychology, University of North Carolina Wilmington, Wilmington, North Carolina, USA.

The present study aimed to examine the role of positive problem solving in the relation between perspective taking and relationship satisfaction.Participants: One hundred and four college students participated in the present study, if they had been in a romantic relationship for a minimum of six months. Participants completed measures of relationship satisfaction, perspective-taking relative to romantic couples, and of positive problem-solving in couples. As predicted, both perspective-taking and positive problem-solving were significantly related to relationship satisfaction. In addition, positive problem-solving emerged as a significant partial mediator of the relation between perspective-taking and relationship satisfaction. The benefits of skills training in the areas of perspective-taking and problem-solving in college student health and functioning are discussed.
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http://dx.doi.org/10.1080/07448481.2021.1909044DOI Listing
July 2021

Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade.

Nat Med 2021 08 8;27(8):1432-1441. Epub 2021 Jul 8.

Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.

Treatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical benefit across tumor types, but also a high rate of immune-related adverse events. Insights into biomarkers and mechanisms of response and toxicity to CICB are needed. To address this, we profiled the blood, tumor and gut microbiome of 77 patients with advanced melanoma treated with CICB, with a high rate of any ≥grade 3 immune-related adverse events (49%) with parallel studies in pre-clinical models. Tumor-associated immune and genomic biomarkers of response to CICB were similar to those identified for ICB monotherapy, and toxicity from CICB was associated with a more diverse peripheral T-cell repertoire. Profiling of gut microbiota demonstrated a significantly higher abundance of Bacteroides intestinalis in patients with toxicity, with upregulation of mucosal IL-1β in patient samples of colitis and in pre-clinical models. Together, these data offer potential new therapeutic angles for targeting toxicity to CICB.
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http://dx.doi.org/10.1038/s41591-021-01406-6DOI Listing
August 2021

Corticosterone Administration Alters White Matter Tract Structure and Reduces Gliosis in the Sub-Acute Phase of Experimental Stroke.

Int J Mol Sci 2021 Jun 22;22(13). Epub 2021 Jun 22.

School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan 2308, Australia.

White matter tract (WMT) degeneration has been reported to occur following a stroke, and it is associated with post-stroke functional disturbances. White matter pathology has been suggested to be an independent predictor of post-stroke recovery. However, the factors that influence WMT remodeling are poorly understood. Cortisol is a steroid hormone released in response to prolonged stress, and elevated levels of cortisol have been reported to interfere with brain recovery. The objective of this study was to investigate the influence of corticosterone (CORT; the rodent equivalent of cortisol) on WMT structure post-stroke. Photothrombotic stroke (or sham surgery) was induced in 8-week-old male C57BL/6 mice. At 72 h, mice were exposed to standard drinking water ± CORT (100 µg/mL). After two weeks of CORT administration, mice were euthanised and brain tissue collected for histological and biochemical analysis of WMT (particularly the corpus callosum and corticospinal tract). CORT administration was associated with increased tissue loss within the ipsilateral hemisphere, and modest and inconsistent WMT reorganization. Further, a structural and molecular analysis of the WMT components suggested that CORT exerted effects over axons and glial cells. Our findings highlight that CORT at stress-like levels can moderately influence the reorganization and microstructure of WMT post-stroke.
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http://dx.doi.org/10.3390/ijms22136693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269094PMC
June 2021

Helping parents provide vegetable snacks: Investigating price and taste as barriers.

Appetite 2021 11 25;166:105481. Epub 2021 Jun 25.

Friedman School of Nutrition Science and Policy, Tufts University, 150 Harrison Ave., Boston, MA, 02111, USA. Electronic address:

Snacks contribute nearly one-quarter of children's daily energy intake in the USA. Snack time therefore represents an opportunity for parents to provide foods with key nutrients. Instead, the most common snack foods are major contributors to children's consumption of added sugars and sodium. Parents face major barriers to providing healthier snacks, including perceptions of high cost and lack of child acceptance. We obtained both economic and qualitative data to inform and optimize interventions for parents to promote vegetable snacks for children. We conducted a survey with parents (n = 368) to estimate how much of a discount would influence vegetable snack purchases by estimating willingness-to-pay using the contingent valuation method, using baby-cut carrots as a sample product. We conducted three focus groups (n = 19) and 1 group interview (n = 2) with children to help understand how to increase the appeal of vegetable snacks. Most (70%) parents accepted the reference price for the vegetable snack. Among those who did not, contingent valuation analysis revealed that a mean discount of approximately 30% would shift consumers to purchasing the snack. Focus group results revealed that the appeal of vegetable snacks to children was influenced by how they were prepared and presented, and the child's familiarity with the vegetables and ability to choose among them. This study lays the groundwork for effective interventions to promote the provision of vegetable snacks by parents.
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http://dx.doi.org/10.1016/j.appet.2021.105481DOI Listing
November 2021

Wave reflection: More than a round trip.

Med Eng Phys 2021 06 30;92:40-44. Epub 2021 Apr 30.

School of Engineering, The Unviersity of Newcastle, Australia. Electronic address:

Reflected pressure waves are key to the understanding of vascular ageing, a prominent factor in major cardiovascular events. Several different metrics have been proposed to index the effect of wave reflection on the pressure waveform and thereby serve as an indicator of vascular ageing. The extent to which these indices are influenced by factors other than vascular health remains a matter of concern. In this paper, we use transmission-line theory to derive a mathematical model for the reflection time (T), and the augmentation index (AI), assuming a general extended model of the arterial system. Then, we test the proposed model against values reported in the literature. Finally, we discuss insights from the model to common observations in the literature such as age-related "shift" in the reflection site, the variation of AI with heart rate, and the flattening of T in older participants.
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http://dx.doi.org/10.1016/j.medengphy.2021.04.005DOI Listing
June 2021

Public health utility of cause of death data: applying empirical algorithms to improve data quality.

BMC Med Inform Decis Mak 2021 06 2;21(1):175. Epub 2021 Jun 2.

Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.

Background: Accurate, comprehensive, cause-specific mortality estimates are crucial for informing public health decision making worldwide. Incorrectly or vaguely assigned deaths, defined as garbage-coded deaths, mask the true cause distribution. The Global Burden of Disease (GBD) study has developed methods to create comparable, timely, cause-specific mortality estimates; an impactful data processing method is the reallocation of garbage-coded deaths to a plausible underlying cause of death. We identify the pattern of garbage-coded deaths in the world and present the methods used to determine their redistribution to generate more plausible cause of death assignments.

Methods: We describe the methods developed for the GBD 2019 study and subsequent iterations to redistribute garbage-coded deaths in vital registration data to plausible underlying causes. These methods include analysis of multiple cause data, negative correlation, impairment, and proportional redistribution. We classify garbage codes into classes according to the level of specificity of the reported cause of death (CoD) and capture trends in the global pattern of proportion of garbage-coded deaths, disaggregated by these classes, and the relationship between this proportion and the Socio-Demographic Index. We examine the relative importance of the top four garbage codes by age and sex and demonstrate the impact of redistribution on the annual GBD CoD rankings.

Results: The proportion of least-specific (class 1 and 2) garbage-coded deaths ranged from 3.7% of all vital registration deaths to 67.3% in 2015, and the age-standardized proportion had an overall negative association with the Socio-Demographic Index. When broken down by age and sex, the category for unspecified lower respiratory infections was responsible for nearly 30% of garbage-coded deaths in those under 1 year of age for both sexes, representing the largest proportion of garbage codes for that age group. We show how the cause distribution by number of deaths changes before and after redistribution for four countries: Brazil, the United States, Japan, and France, highlighting the necessity of accounting for garbage-coded deaths in the GBD.

Conclusions: We provide a detailed description of redistribution methods developed for CoD data in the GBD; these methods represent an overall improvement in empiricism compared to past reliance on a priori knowledge.
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http://dx.doi.org/10.1186/s12911-021-01501-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170729PMC
June 2021

The Grayness of the Origin of Life.

Life (Basel) 2021 May 29;11(6). Epub 2021 May 29.

Department of Biology, Georgetown University, Washington, DC 20057, USA.

In the search for life beyond Earth, distinguishing the living from the non-living is paramount. However, this distinction is often elusive, as the origin of life is likely a stepwise evolutionary process, not a singular event. Regardless of the favored origin of life model, an inherent "grayness" blurs the theorized threshold defining life. Here, we explore the ambiguities between the biotic and the abiotic at the origin of life. The role of grayness extends into later transitions as well. By recognizing the limitations posed by grayness, life detection researchers will be better able to develop methods sensitive to prebiotic chemical systems and life with alternative biochemistries.
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http://dx.doi.org/10.3390/life11060498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226951PMC
May 2021

TRIP13 modulates protein deubiquitination and accelerates tumor development and progression of B cell malignancies.

J Clin Invest 2021 Jul;131(14)

Myeloma Center, Winthrop P. Rockefeller Institute, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.

Multiple myeloma (MM), a terminally differentiated B cell malignancy, remains difficult to cure. Understanding the molecular mechanisms underlying the progression of MM may identify therapeutic targets and lead to a fundamental shift in treatment of the disease. Deubiquitination, like ubiquitination, is a highly regulated process, implicated in almost every cellular process. Multiple deubiquitinating enzymes (DUBs) have been identified, but their regulation is poorly defined. Here, we determined that TRIP13 increases cellular deubiquitination. Overexpression of TRIP13 in mice and cultured cells resulted in excess cellular deubiquitination by enhancing the association of the DUB USP7 with its substrates. We show that TRIP13 is an oncogenic protein because it accelerates B cell tumor development in transgenic mice. TRIP13-induced resistance to proteasome inhibition can be overcome by a USP7 inhibitor in vitro and in vivo. These findings suggest that TRIP13 expression plays a critical role in B cell lymphoma and MM by regulating deubiquitination of critical oncogenic (NEK2) and tumor suppressor (PTEN, p53) proteins. High TRIP13 identifies a high-risk patient group amenable to adjuvant anti-USP7 therapy.
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http://dx.doi.org/10.1172/JCI146893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279583PMC
July 2021

Associations of adverse childhood experiences with stress physiology and insulin resistance in adolescents at risk for adult obesity.

Dev Psychobiol 2021 Sep 15;63(6):e22127. Epub 2021 May 15.

Department of Human Development and Family Studies, Colorado State University, Fort Collins, Colorado, USA.

Adverse childhood experiences (ACEs) heighten the risk for adult obesity and cardiometabolic disease, but physiological factors underlying this connection are not well understood. We determined if ACEs were associated with physiological stress response and insulin resistance in adolescents at risk for adult obesity. Participants were 90 adolescents 12.0-17.5 years (50% female, 30% Hispanic/Latinx), at risk for adult obesity by virtue of above-average body mass index (BMI; kg/m ≥ 70th percentile) or parental obesity (BMI ≥ 30 kg/m ). ACEs were determined as presence (vs. absence) based upon the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Physiological stress response was measured as heart rate/blood pressure response to the Trier Social Stress Test. Homeostatic model assessment of insulin resistance was determined from fasting glucose/insulin. Sixty-one percent of adolescents reported positive ACE history. The presence of ACEs predicted greater heart rate (p < .001) and diastolic blood pressure (p = .02) response to stress, controlling for age, sex, race/ethnicity, puberty, and BMI standard score. Systolic blood pressure and insulin resistance did not differ by ACE history (p-values > .08). Findings suggest heightened sympathetic stress response in adolescence could be explanatory in how ACEs increase the risk for later cardiometabolic disease. Future studies should characterize ACEs in relationship to day-to-day variations in adolescents' stress physiology and glucose homeostasis.
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http://dx.doi.org/10.1002/dev.22127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410633PMC
September 2021

Tobacco smoking and mental disorders in Australian adolescents.

Aust N Z J Psychiatry 2021 Apr 28:48674211009617. Epub 2021 Apr 28.

School of Psychology and Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.

Objectives: This study aimed to (1) examine the strength of the association between mental disorders/mental health problems, risk behaviours and tobacco smoking among Australian adolescents, (2) compare rates of tobacco smoking among Australian adolescents with major depressive disorder, attention-deficit/hyperactivity disorder and/or conduct disorder in 2013/14 vs 1998, and (3) identify the extent to which an association between tobacco smoking and mental health problems among adolescents can be attributed to non-mental health risk factors.

Methods: The study utilised data from the first (1998) and second (2013/14) child and adolescent components of the National Surveys of Mental Health and Wellbeing. Both surveys identified nationally representative samples of Australian young people aged 4-17 years, living in private dwellings. Information was collected from parents and 13- to 17-year-olds about mental disorders, mental health problems, risk behaviours and tobacco smoking.

Results: In the 2013/14 survey, the rate of current tobacco smoking among those with a mental disorder was 20% compared to 5% in those without a mental disorder. Rates were highest for young people with conduct disorder (50%), major depressive disorder (24%) and anxiety disorders (19%). In 2013/14, 38% of current tobacco smokers had a mental disorder and 32% reported self-harm and/or suicidal ideation vs 10% and 5%, respectively, among adolescents who had never smoked. Females with mental disorders or reporting self-harm or suicidal ideation had higher rates of current smoking than males. Other significant factors associated with current smoking included school-related problems, binge eating and having had more than one sexual partner.

Conclusion: While smoking rates in 13- to 17-year-olds with mental disorders had declined since 1998, the strength of the association between mental disorders and smoking had increased, especially among females. Our findings highlight the need to address the tobacco smoking among adolescents with mental disorders, particularly females.
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http://dx.doi.org/10.1177/00048674211009617DOI Listing
April 2021

Dynamics of sputum conversion during effective tuberculosis treatment: A systematic review and meta-analysis.

PLoS Med 2021 04 26;18(4):e1003566. Epub 2021 Apr 26.

TB Centre, London School of Hygiene & Tropical Medicine, London, United Kingdom.

Background: Two weeks' isolation is widely recommended for people commencing treatment for pulmonary tuberculosis (TB). The evidence that this corresponds to clearance of potentially infectious tuberculous mycobacteria in sputum is not well established. This World Health Organization-commissioned review investigated sputum sterilisation dynamics during TB treatment.

Methods And Findings: For the main analysis, 2 systematic literature searches of OvidSP MEDLINE, Embase, and Global Health, and EBSCO CINAHL Plus were conducted to identify studies with data on TB infectiousness (all studies to search date, 1 December 2017) and all randomised controlled trials (RCTs) for drug-susceptible TB (from 1 January 1990 to search date, 20 February 2018). Included articles reported on patients receiving effective treatment for culture-confirmed drug-susceptible pulmonary TB. The outcome of interest was sputum bacteriological conversion: the proportion of patients having converted by a defined time point or a summary measure of time to conversion, assessed by smear or culture. Any study design with 10 or more particpants was considered. Record sifting and data extraction were performed in duplicate. Random effects meta-analyses were performed. A narrative summary additionally describes the results of a systematic search for data evaluating infectiousness from humans to experimental animals (PubMed, all studies to 27 March 2018). Other evidence on duration of infectiousness-including studies reporting on cough dynamics, human tuberculin skin test conversion, or early bactericidal activity of TB treatments-was outside the scope of this review. The literature search was repeated on 22 November 2020, at the request of the editors, to identify studies published after the previous censor date. Four small studies reporting 3 different outcome measures were identified, which included no data that would alter the findings of the review; they are not included in the meta-analyses. Of 5,290 identified records, 44 were included. Twenty-seven (61%) were RCTs and 17 (39%) were cohort studies. Thirteen studies (30%) reported data from Africa, 12 (27%) from Asia, 6 (14%) from South America, 5 (11%) from North America, and 4 (9%) from Europe. Four studies reported data from multiple continents. Summary estimates suggested smear conversion in 9% of patients at 2 weeks (95% CI 3%-24%, 1 single study [N = 1]), and 82% of patients at 2 months of treatment (95% CI 78%-86%, N = 10). Among baseline smear-positive patients, solid culture conversion occurred by 2 weeks in 5% (95% CI 0%-14%, N = 2), increasing to 88% at 2 months (95% CI 84%-92%, N = 20). At equivalent time points, liquid culture conversion was achieved in 3% (95% CI 1%-16%, N = 1) and 59% (95% CI 47%-70%, N = 8). Significant heterogeneity was observed. Further interrogation of the data to explain this heterogeneity was limited by the lack of disaggregation of results, including by factors such as HIV status, baseline smear status, and the presence or absence of lung cavitation.

Conclusions: This systematic review found that most patients remained culture positive at 2 weeks of TB treatment, challenging the view that individuals are not infectious after this interval. Culture positivity is, however, only 1 component of infectiousness, with reduced cough frequency and aerosol generation after TB treatment initiation likely to also be important. Studies that integrate our findings with data on cough dynamics could provide a more complete perspective on potential transmission of Mycobacterium tuberculosis by individuals on treatment.

Trial Registration: Systematic review registration: PROSPERO 85226.
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http://dx.doi.org/10.1371/journal.pmed.1003566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109831PMC
April 2021

The role of mindfulness in associations among depression symptoms, sleep duration, and insulin resistance in adolescents.

J Behav Med 2021 Apr 21. Epub 2021 Apr 21.

Department of Human Development and Family Studies, Colorado State University, 1570 Campus Delivery, Fort Collins, CO, 80523-1570, US.

Sleep difficulties may be one explanatory factor in the association between depression and insulin resistance; yet, explicit tests of this hypothesis are lacking. We determined if there was an indirect effect of depression symptoms on insulin resistance through sleep duration in adolescents at risk for excess weight gain. We also investigated whether dispositional mindfulness moderated the interconnections among depression, sleep, and insulin resistance. Ninety adolescents (14.2 ± 1.6y; 50% female) at risk for excess weight gain (body mass index [BMI, kg/m] z score 1.6 ± 0.6) participated in the cross-sectional, baseline phase of a health behaviors study. Depression was assessed with the Center for Epidemiologic Studies-Depression Scale, sleep duration with the Sleep Habits Survey, and mindfulness with the Mindful Attention and Awareness Scale. Homeostatic model assessment of insulin resistance was determined from fasting insulin and glucose. The product-of-coefficients method was used to test the indirect effect of depression on insulin resistance through sleep duration, accounting for age, sex, BMIz, puberty, and socioeconomic status (SES). Dispositional mindfulness was tested as a moderator of the associations among depression, sleep, and insulin resistance. There was a significant indirect effect of depression on insulin resistance through sleep duration, controlling for age, sex, BMIz, puberty, and SES, 95%CI [0.001, 0.05]. Dispositional mindfulness moderated the association between sleep duration and insulin resistance, such that lower sleep duration related to greater insulin resistance only among adolescents with lower mindfulness (p < .001). Short sleep may be one explanatory factor in the depression-insulin resistance connection in adolescents at risk for excess weight gain. Adolescents with poorer mindfulness and short sleep are at highest risk for insulin resistance, whereas higher mindfulness may be protective.
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http://dx.doi.org/10.1007/s10865-021-00225-xDOI Listing
April 2021

Exploring How Low Oxygen Post Conditioning Improves Stroke-Induced Cognitive Impairment: A Consideration of Amyloid-Beta Loading and Other Mechanisms.

Front Neurol 2021 24;12:585189. Epub 2021 Mar 24.

School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.

Cognitive impairment is a common and disruptive outcome for stroke survivors, which is recognized to be notoriously difficult to treat. Previously, we have shown that low oxygen post-conditioning (LOPC) improves motor function and limits secondary neuronal loss in the thalamus after experimental stroke. There is also emerging evidence that LOPC may improve cognitive function post-stroke. In the current study we aimed to explore how exposure to LOPC may improve cognition post-stroke. Experimental stroke was induced using photothrombotic occlusion in adult, male C57BL/6 mice. At 72 h post-stroke animals were randomly assigned to either normal atmospheric air or to one of two low oxygen (11% O) exposure groups (either 8 or 24 h/day for 14 days). Cognition was assessed during the treatment phase using a touchscreen based paired-associate learning assessment. At the end of treatment (17 days post-stroke) mice were euthanized and tissue was collected for subsequent histology and biochemical analysis. LOPC (both 8 and 24 h) enhanced learning and memory in the 2nd week post-stroke when compared with stroke animals exposed to atmospheric air. Additionally we observed LOPC was associated with lower levels of neuronal loss, the restoration of several vascular deficits, as well as a reduction in the severity of the amyloid-beta (Aβ) burden. These findings provide further insight into the pro-cognitive benefits of LOPC.
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http://dx.doi.org/10.3389/fneur.2021.585189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024636PMC
March 2021

A Person-centered Approach to Violence Exposure in Postwar Colombian Youth: Demographic Covariates and Positive Youth Development Outcomes.

J Interpers Violence 2021 Apr 9:8862605211005136. Epub 2021 Apr 9.

Arizona State University, Tempe, AZ, United States.

While the negative impact of extensive exposure to community violence and armed conflict is known, less emphasis has been focused on outcomes supportive of resilience. It is critical to begin exploring these constructs to both promote healing from decades-long conflict and to inform targeted interventions that focus on positive youth development in contexts of adversity. This study thus utilized a person-centered approach to estimate violence exposure profiles among 3,443 Colombian youth to explore what demographic covariates and positive youth development outcomes, such as school engagement, hope, goals, social competence, future expectations, and barriers to education were associated with each violence exposure profile. Four profiles emerged: a low exposure profile, a high community violence profile, a some combined exposure profile, and a high combined exposure profile, each with various levels of community violence witnessing and victimization as well as armed conflict exposure. Demographic covariance results showed older, urban, male youth were more likely to be in the high violence exposure profiles compared to the low exposure group. Youth in the high combined exposure profile were more likely to have lower hope, educational expectations, and social competence compared to the low exposure group. Findings highlight that a person-centered approach provides a more multidimensional view of adolescent violence exposure. Demographic differences suggested the importance of tailoring violence prevention initiatives to the local context. Finally, results concerning positive youth development outcomes suggest that resiliency-oriented constructs, which can be instrumental toward youth's postwar healing and growth, should be emphasized among populations who experience high levels of co-occurring exposure.
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http://dx.doi.org/10.1177/08862605211005136DOI Listing
April 2021

A new compressible hyperelastic model for the multi-axial deformation of blood clot occlusions in vessels.

Biomech Model Mechanobiol 2021 Aug 5;20(4):1317-1335. Epub 2021 Apr 5.

Biomedical Engineering, National University of Ireland Galway, Galway, Ireland.

Mechanical thrombectomy can be significantly affected by the mechanical properties of the occluding thrombus. In this study, we provide the first characterisation of the volumetric behaviour of blood clots. We propose a new hyperelastic model for the volumetric and isochoric deformation of clot. We demonstrate that the proposed model provides significant improvements over established models in terms of accurate prediction of nonlinear stress-strain and volumetric behaviours of clots with low and high red blood cell compositions. We perform a rigorous investigation of the factors that govern clot occlusion of a tapered vessel. The motivation for such an analysis is twofold: (i) the role of clot composition on the in vivo occlusion location is an open clinical question that has significant implications for thrombectomy procedures; (ii) in vitro measurement of occlusion location in an engineered tapered tube can be used as a quick and simple methodology to assess the mechanical properties/compositions of clots. Simulations demonstrate that both isochoric and volumetric behaviours of clots are key determinants of clot lodgement location, in addition to clot-vessel friction. The proposed formulation is shown to provide accurate predictions of in vitro measurement of clot occlusion location in a silicone tapered vessel, in addition to accurately predicting the deformed shape of the clot.
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http://dx.doi.org/10.1007/s10237-021-01446-4DOI Listing
August 2021
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