Corrigendum: Paraburkholderia madseniana sp. nov., a phenolic acid-degrading bacterium isolated from acidic forest soil.
Int J Syst Evol Microbiol. 2020 Dec;70(12):6534-6538
Authors: Wilhelm RC, Murphy SJL, Feriancek NM, Karasz DC, DeRito CM, Newman JD, Buckley DH
PMID: 33351737 [PubMed - as supplied by publisher]
Advances in meningioma genomics, proteomics, and epigenetics: insights into biomarker identification and targeted therapies.
Oncotarget. 2020 Dec 08;11(49):4544-4553
Authors: Nazem AA, Ruzevick J, Ferreira MJ
Abstract
Meningiomas are a heterogeneous group of tumors, defined histo-pathologically by World Health Organization (WHO) grading. The WHO grade of meningiomas does not always correlate with clinical aggressiveness. Despite maximal surgical resection and adjuvant radiation, a subset of tumors are clinically aggressive; displaying early recurrence and invasion. Current methods for identifying aggressive meningiomas solely focus on genomics, proteomics, or epigenetics and not a combination of all for developing a real-time clinical biomarker. Improved methods for the identification of these outlying tumors can facilitate better classification and potentially adjuvant treatment planning. Understanding the pathways of oncogenesis using multiple markers driving aggressive meningiomas can provide a foundation for targeted therapies, which currently do not exist.
PMID: 33346248 [PubMed]
Pain anxiety and rehabilitation outcomes after acquired brain injury.
Brain Inj. 2020 Dec 21;:1-9
Authors: Williams MW, Rapport LJ, Sander AM, Parker HA
Abstract
Purpose: The purpose of this study was to examine pain anxiety after acquired brain injury (ABI) and its relationship to rehabilitation outcomes. Materials and Method: Participants consisted of 89 adults with an ABI participating in outpatient rehabilitation therapy. They completed a battery of neuropsychological tests at baseline along with surveys of mood, health-related self-efficacy, and pain anxiety. Separately, occupational therapists assessed basic and instrumental activities of daily living (ADLs) as well as therapy engagement across treatment after the sixth session. Results: Individuals who reported high pain anxiety had fewer years of formal education, lower self-efficacy, and more emotional distress than those with low pain anxiety. Although Blacks were about half (56%) of the study sample, they comprised the majority (73.1%) of individuals in the high pain anxiety group. Pain anxiety was negatively related to therapy engagement. Moderation analysis using linear regression indicated that pain anxiety moderated the influence of self-efficacy on basic ADLs. Conclusions: Pain anxiety, particularly when high, is negatively associated with rehabilitation outcomes for individuals with ABI. Among those with high pain anxiety, health-related self-efficacy is an important resilience characteristic to improve functional outcomes. In rehabilitation therapy, pain anxiety provides a novel intervention target to enhance ABI recovery.
PMID: 33347375 [PubMed - as supplied by publisher]
A clinical protocol of a comparative effectiveness trial of extended-release naltrexone versus extended-release buprenorphine with individuals leaving jail.
J Subst Abuse Treat. 2020 Dec 11;:108241
Authors: Gordon MS, Mitchell SG, Blue TR, Vocci FJ, Fishman MJ, Murphy SM, Couvillion K, Maher K, Ryan D, Wenzel K, Danner ML, Jarvis DK
Abstract
This study is a randomized, open label, controlled trial of extended-release buprenorphine (XR-B; BRIXADI™ formulation) versus extended-release naltrexone (XR-NTX) in Maryland jails. A 7-site, open-label, equivalence design will randomly assign 240 adults with a history of opioid use disorder (OUD), stratified by gender and jail, who are nearing release to one of two treatment arms: 1) XR-B in jail or 2) XR-NTX in jail, both followed by 6 monthly injections postrelease at a community treatment program. The primary aim is to determine the rate of pharmacotherapy adherence (number of monthly injections received) of XR-B compared to XR-NTX. The proposed study is innovative because it will be the first randomized clinical trial in the U.S. assessing the effectiveness of receiving XR-B vs. XR-NTX in county jails. The public health impact of the study will be highly significant and far-reaching because most individuals with OUD do not receive treatment while incarcerated, thereby substantially raising their likelihood of relapse to drug use, overdose death, and re-incarceration. Understanding how to expand acceptance of medications for OUD in jails, particularly extended-release medications, and supporting treatment engagement and medication adherence in transition to the community, has far-reaching implications for improving treatment access and success in this population.
PMID: 33339633 [PubMed - as supplied by publisher]
Directed differentiation into insulin-producing cells using microRNA manipulation.
Open Med (Wars). 2020;15(1):567-570
Authors: Williams MD, Joglekar MV, Hardikar AA, Wong WKM
Abstract
Our commentary is focused on three studies that used microRNA overexpression methods for directed differentiation of stem cells into insulin-producing cells. Islet transplantation is the only cell-based therapy used to treat type 1 diabetes mellitus. However, due to the scarcity of cadaveric donors and limited availability of good quality and quantity of islets for transplant, alternate sources of insulin-producing cells are being studied and used by researchers. This commentary provides an overview of distinct studies focused on manipulating microRNA expression to optimize differentiation of embryonic stem cells or induced pluripotent stem cells into insulin-producing cells. These studies have used different approaches to overexpress microRNAs that are highly abundant in human islets (such as miR-375 and miR-7) in their differentiation protocol to achieve better differentiation into functional islet beta (β)-cells.
PMID: 33336012 [PubMed]
Building longitudinal medication dose data using medication information extracted from clinical notes in electronic health records.
J Am Med Inform Assoc. 2020 Dec 18;:
Authors: McNeer E, Beck C, Weeks HL, Williams ML, James NT, Bejan CA, Choi L
Abstract
OBJECTIVE: To develop an algorithm for building longitudinal medication dose datasets using information extracted from clinical notes in electronic health records (EHRs).
MATERIALS AND METHODS: We developed an algorithm that converts medication information extracted using natural language processing (NLP) into a usable format and builds longitudinal medication dose datasets. We evaluated the algorithm on 2 medications extracted from clinical notes of Vanderbilt's EHR and externally validated the algorithm using clinical notes from the MIMIC-III clinical care database.
RESULTS: For the evaluation using Vanderbilt's EHR data, the performance of our algorithm was excellent; F1-measures were ≥0.98 for both dose intake and daily dose. For the external validation using MIMIC-III, the algorithm achieved F1-measures ≥0.85 for dose intake and ≥0.82 for daily dose.
DISCUSSION: Our algorithm addresses the challenge of building longitudinal medication dose data using information extracted from clinical notes. Overall performance was excellent, but the algorithm can perform poorly when incorrect information is extracted by NLP systems. Although it performed reasonably well when applied to the external data source, its performance was worse due to differences in the way the drug information was written. The algorithm is implemented in the R package, "EHR," and the extracted data from Vanderbilt's EHRs along with the gold standards are provided so that users can reproduce the results and help improve the algorithm.
CONCLUSION: Our algorithm for building longitudinal dose data provides a straightforward way to use EHR data for medication-based studies. The external validation results suggest its potential for applicability to other systems.
PMID: 33338223 [PubMed - as supplied by publisher]
Predictors of fast and ultrafast shunt failure in pediatric hydrocephalus: a Hydrocephalus Clinical Research Network study.
J Neurosurg Pediatr. 2020 Dec 18;:1-10
Authors: Hauptman JS, Kestle J, Riva-Cambrin J, Kulkarni AV, Browd SR, Rozzelle CJ, Whitehead WE, Naftel RP, Pindrik J, Limbrick DD, Drake J, Wellons JC, Tamber MS, Shannon CN, Simon TD, Pollack IF, McDonald PJ, Krieger MD, Chu J, Hankinson TC, Jackson EM, Alvey JS, Reeder RW, Holubkov R, Hydrocephalus Clinical Research Network
Abstract
OBJECTIVE: The primary objective of this study was to use the prospective Hydrocephalus Clinical Research Network (HCRN) registry to determine clinical predictors of fast time to shunt failure (≤ 30 days from last revision) and ultrafast time to failure (≤ 7 days from last revision).
METHODS: Revisions (including those due to infection) to permanent shunt placements that occurred between April 2008 and November 2017 for patients whose entire shunt experience was recorded in the registry were analyzed. All registry data provided at the time of initial shunt placement and subsequent revision were reviewed. Key variables analyzed included etiology of hydrocephalus, age at time of initial shunt placement, presence of slit ventricles on imaging at revision, whether the ventricles were enlarged at the time of revision, and presence of prior fast failure events. Univariable and multivariable analyses were performed to find key predictors of fast and ultrafast failure events.
RESULTS: A cohort of 1030 patients with initial shunt insertions experienced a total of 1995 revisions. Of the 1978 revision events with complete records, 1216 (61.5%) shunts remained functional for more than 1 year, and 762 (38.5%) failed within 1 year of the procedure date. Of those that failed within 1 year, 423 (55.5%) failed slowly (31-365 days) and 339 (44.5%) failed fast (≤ 30 days). Of the fast failures, 131 (38.6%) were ultrafast (≤ 7 days). In the multivariable analysis specified a priori, etiology of hydrocephalus (p = 0.005) and previous failure history (p = 0.011) were independently associated with fast failure. Age at time of procedure (p = 0.042) and etiology of hydrocephalus (p = 0.004) were independently associated with ultrafast failure. These relationships in both a priori models were supported by the data-driven multivariable models as well.
CONCLUSIONS: Neither the presence of slit ventricle syndrome nor ventricular enlargement at the time of shunt failure appears to be a significant predictor of repeated, rapid shunt revisions. Age at the time of procedure, etiology of hydrocephalus, and the history of previous failure events seem to be important predictors of fast and ultrafast shunt failure. Further work is required to understand the mechanisms of these risk factors as well as mitigation strategies.
PMID: 33338993 [PubMed - as supplied by publisher]
Preparing for Life: Plasma Proteome Changes and Immune System Development During the First Week of Human Life.
Front Immunol. 2020;11:578505
Authors: Bennike TB, Fatou B, Angelidou A, Diray-Arce J, Falsafi R, Ford R, Gill EE, van Haren SD, Idoko OT, Lee AH, Ben-Othman R, Pomat WS, Shannon CP, Smolen KK, Tebbutt SJ, Ozonoff A, Richmond PC, van den Biggelaar AHJ, Hancock REW, Kampmann B, Kollmann TR, Levy O, Steen H
Abstract
Neonates have heightened susceptibility to infections. The biological mechanisms are incompletely understood but thought to be related to age-specific adaptations in immunity due to resource constraints during immune system development and growth. We present here an extended analysis of our proteomics study of peripheral blood-plasma from a study of healthy full-term newborns delivered vaginally, collected at the day of birth and on day of life (DOL) 1, 3, or 7, to cover the first week of life. The plasma proteome was characterized by LC-MS using our established 96-well plate format plasma proteomics platform. We found increasing acute phase proteins and a reduction of respective inhibitors on DOL1. Focusing on the complement system, we found increased plasma concentrations of all major components of the classical complement pathway and the membrane attack complex (MAC) from birth onward, except C7 which seems to have near adult levels at birth. In contrast, components of the lectin and alternative complement pathways mainly decreased. A comparison to whole blood messenger RNA (mRNA) levels enabled characterization of mRNA and protein levels in parallel, and for 23 of the 30 monitored complement proteins, the whole blood transcript information by itself was not reflective of the plasma protein levels or dynamics during the first week of life. Analysis of immunoglobulin (Ig) mRNA and protein levels revealed that IgM levels and synthesis increased, while the plasma concentrations of maternally transferred IgG1-4 decreased in accordance with their in vivo half-lives. The neonatal plasma ratio of IgG1 to IgG2-4 was increased compared to adult values, demonstrating a highly efficient IgG1 transplacental transfer process. Partial compensation for maternal IgG degradation was achieved by endogenous synthesis of the IgG1 subtype which increased with DOL. The findings were validated in a geographically distinct cohort, demonstrating a consistent developmental trajectory of the newborn's immune system over the first week of human life across continents. Our findings indicate that the classical complement pathway is central for newborn immunity and our approach to characterize the plasma proteome in parallel with the transcriptome will provide crucial insight in immune ontogeny and inform new approaches to prevent and treat diseases.
PMID: 33329546 [PubMed - in process]
Multi-Omic Data Integration Allows Baseline Immune Signatures to Predict Hepatitis B Vaccine Response in a Small Cohort.
Front Immunol. 2020;11:578801
Authors: Shannon CP, Blimkie TM, Ben-Othman R, Gladish N, Amenyogbe N, Drissler S, Edgar RD, Chan Q, Krajden M, Foster LJ, Kobor MS, Mohn WW, Brinkman RR, Le Cao KA, Scheuermann RH, Tebbutt SJ, Hancock REW, Koff WC, Kollmann TR, Sadarangani M, Lee AH
Abstract
Background: Vaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts.
Methods: We applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres.
Results: Using both an unsupervised molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Biological associations were unravelled, with signalling pathways such as JAK-STAT and interleukin signalling, Toll-like receptor cascades, interferon signalling, and Th17 cell differentiation emerging as important pre-vaccination modulators of response.
Conclusion: This study provides further evidence that baseline cellular and molecular characteristics of an individual's immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets.
PMID: 33329547 [PubMed - in process]
A Bovine Enteric Mycobacterium Infection Model to Analyze Parenteral Vaccine-Induced Mucosal Immunity and Accelerate Vaccine Discovery.
Front Immunol. 2020;11:586659
Authors: Facciuolo A, Lee AH, Trimble MJ, Rawlyk N, Townsend HGG, Bains M, Arsic N, Mutharia LM, Potter A, Gerdts V, Napper S, Hancock REW, Griebel PJ
Abstract
Mycobacterial diseases of cattle are responsible for considerable production losses worldwide. In addition to their importance in animals, these infections offer a nuanced approach to understanding persistent mycobacterial infection in native host species. Mycobacterium avium ssp. paratuberculosis (MAP) is an enteric pathogen that establishes a persistent, asymptomatic infection in the small intestine. Difficulty in reproducing infection in surrogate animal models and limited understanding of mucosal immune responses that control enteric infection in the natural host have been major barriers to MAP vaccine development. We previously developed a reproducible challenge model to establish a consistent MAP infection using surgically isolated intestinal segments prepared in neonatal calves. In the current study, we evaluated whether intestinal segments could be used to screen parenteral vaccines that alter mucosal immune responses to MAP infection. Using Silirum® - a commercial MAP bacterin - we demonstrate that intestinal segments provide a platform for assessing vaccine efficacy within a relatively rapid period of 28 days post-infection. Significant differences between vaccinates and non-vaccinates could be detected using quantitative metrics including bacterial burden in intestinal tissue, MAP shedding into the intestinal lumen, and vaccine-induced mucosal immune responses. Comparing vaccine-induced responses in mucosal leukocytes isolated from the site of enteric infection versus blood leukocytes revealed substantial inconsistences between these immune compartments. Moreover, parenteral vaccination with Silirum did not induce equal levels of protection throughout the small intestine. Significant control of MAP infection was observed in the continuous but not the discrete Peyer's patches. Analysis of these regional mucosal immune responses revealed novel correlates of immune protection associated with reduced infection that included an increased frequency of CD335+ innate lymphoid cells, and increased expression of IL21 and IL27. Thus, intestinal segments provide a novel model to accelerate vaccine screening and discovery by testing vaccines directly in the natural host and provides a unique opportunity to interrogate mucosal immune responses to mycobacterial infections.
PMID: 33329565 [PubMed - in process]
Activation of the Gluteus Maximus During Performance of the Back Squat, Split Squat, and Barbell Hip Thrust and the Relationship With Maximal Sprinting.
J Strength Cond Res. 2021 Jan 01;35(1):16-24
Authors: Williams MJ, Gibson NV, Sorbie GG, Ugbolue UC, Brouner J, Easton C
Abstract
ABSTRACT: Williams, MJ, Gibson, N, Sorbie, GG, Ugbolue, UC, Brouner, J, and Easton, C. Activation of the gluteus maximus during performance of the back squat, split squat, and barbell hip thrust and the relationship with maximal sprinting. J Strength Cond Res 35(1): 16-24, 2021-The purpose of this research was to compare muscle activation of the gluteus maximus and ground reaction force between the barbell hip thrust, back squat, and split squat and to determine the relationship between these outcomes and vertical and horizontal forces during maximal sprinting. Twelve, male, team sport athletes (age, 25.0 ± 4.0 years; stature, 184.1 ± 6.0 cm; body mass, 82.2 ± 7.9 kg) performed separate movements of the 3 strength exercises at a load equivalent to their individual 3 repetition maximum. The ground reaction force was measured using force plates and the electromyography (EMG) activity of the upper and lower gluteus maximus and was recorded in each leg and expressed as percentage of the maximum voluntary isometric contraction (MVIC). Subjects then completed a single sprint on a nonmotorized treadmill for the assessment of maximal velocity and horizontal and vertical forces. Although ground reaction force was lower, peak EMG activity in the gluteus maximus was higher in the hip thrust than in the back squat (p = 0.024; 95% confidence interval [CI] = 4-56% MVIC) and split squat (p = 0.016; 95% CI = 6-58% MVIC). Peak sprint velocity correlated with both anterior-posterior horizontal force (r = 0.72) and peak ground reaction force during the barbell hip thrust (r = 0.69) but no other variables. The increased activation of gluteus maximus during the barbell hip thrust and the relationship with maximal running speed suggests that this movement may be optimal for training this muscle group in comparison to the back squat and split squat.
PMID: 33332802 [PubMed - as supplied by publisher]
Experimental diffuse brain injury and a model of Alzheimer's disease exhibit disease-specific changes in sleep and incongruous peripheral inflammation.
J Neurosci Res. 2020 Dec 14;:
Authors: Saber M, Murphy SM, Cho Y, Lifshitz J, Rowe RK
Abstract
Elderly populations (≥65 years old) have the highest risk of developing Alzheimer's disease (AD) and/or obtaining a traumatic brain injury (TBI). Using translational mouse models, we investigated sleep disturbances and inflammation associated with normal aging, TBI and aging, and AD. We hypothesized that aging results in marked changes in sleep compared with adult mice, and that TBI and aging would result in sleep and inflammation levels similar to AD mice. We used female 16-month-old wild-type (WT Aged) and 3xTg-AD mice, as well as a 2-month-old reference group (WT Adult), to evaluate sleep changes. WT Aged mice received diffuse TBI by midline fluid percussion, and blood was collected from both WT Aged (pre- and post-TBI) and 3xTg-AD mice to evaluate inflammation. Cognitive behavior was tested, and tissue was collected for histology. Bayesian generalized additive and mixed-effects models were used for analyses. Both normal aging and AD led to increases in sleep compared with adult mice. WT Aged mice with TBI slept substantially more, with fragmented shorter bouts, than they did pre-TBI and compared with AD mice. However, differences between WT Aged and 3xTg-AD mice in immune cell populations and plasma cytokine levels were incongruous, cognitive deficits were similar, and cumulative sleep was not predictive of inflammation or behavior for either group. Our results suggest that in similarly aged individuals, TBI immediately induces more profound sleep alterations than in AD, although both diseases likely include cognitive impairments. Unique pathological sleep pathways may exist in elderly individuals who incur TBI compared with similarly aged individuals who have AD, which may warrant disease-specific treatments in clinical settings.
PMID: 33319441 [PubMed - as supplied by publisher]
Comparison of Rates of Overdose and Hospitalization After Initiation of Medication for Opioid Use Disorder in the Inpatient vs Outpatient Setting.
JAMA Netw Open. 2020 12 01;3(12):e2029676
Authors: Morgan JR, Barocas JA, Murphy SM, Epstein RL, Stein MD, Schackman BR, Walley AY, Linas BP
Abstract
Importance: Whereas outpatient treatment with medication for opioid use disorder (MOUD) is evidence based, there is a large network of inpatient facilities in the US that are reimbursed by commercial insurers and do not typically offer MOUD.
Objective: To compare the rates of opioid-related overdose and all-cause hospitalization after outpatient MOUD treatment vs inpatient care.
Design, Setting, and Participants: This comparative effectiveness research study used deidentified claims of commercially insured individuals in the US from the MarketScan Commercial Claims and Encounters Database from January 1, 2010, to December 31, 2017, to obtain a sample of 37 090 individuals with opioid use disorder who initiated treatment with inpatient care and/or MOUD. Data were analyzed from October 1, 2019, to May 1, 2020. To address nonrandom treatment assignment, individuals with opioid use disorder who initiated MOUD or who entered inpatient care were matched 1:1 based on propensity scores.
Exposures: The independent variable of interest was the type of treatment initiated. Individuals could initiate 1 of 5 potential treatments: (1) outpatient MOUD, (2) short-term inpatient care, (3) short-term inpatient care followed by outpatient MOUD within 30 days, (4) long-term inpatient care, or (5) long-term inpatient care followed by outpatient MOUD within 30 days.
Main Outcomes and Measures: Opioid-related overdose and all-cause hospitalization at any point within the 12 months after treatment of opioid use disorder. The hazard for each outcome was estimated using a time-to-event Cox proportional hazards regression model.
Results: The cohort included 37 090 individuals matched 1:1 between inpatient and outpatient treatment (20 723 [56%] were younger than 30 years; 23 250 [63%] were male). After propensity score matching, compared with the inpatient treatments, initiation of outpatient MOUD alone was followed by the lowest 1-year overdose rate (2.2 [95% CI, 2.0-2.5] per 100 person-years vs 3.5 [95% CI, 2.7-4.4] to 7.0 [95% CI, 4.6-10.7] per 100 person-years) and hospitalization rate (39 [95% CI, 38-40] per 100 person-years vs 57 [95% CI, 54-61] to 74 [95% CI, 73-76] per 100 person-years). Outpatient MOUD was also associated with the lowest hazard of these events compared with inpatient care, which had hazard ratios ranging from 1.71 (95% CI, 1.35-2.17) to 2.67 (95% CI, 1.68-4.23) for overdose and 1.33 (95% CI, 1.23-1.44) to 1.90 (95% CI, 1.83-1.97) for hospitalizations.
Conclusions and Relevance: The results of this comparative effectiveness research study suggest that lower rates of subsequent overdose and hospitalization are associated with outpatient MOUD compared with short- or long-term inpatient care. When patients and clinicians have a choice of treatment, outpatient MOUD treatment may be associated with lower overdose and hospitalization on balance. Future research should assess which patients benefit most from inpatient care and how best to leverage existing inpatient treatment infrastructure.
PMID: 33320266 [PubMed - indexed for MEDLINE]
The Western United States has Greater Antibiotic Resistance Among Salmonella Recovered from Intestinal Cecal Samples of Food Animals.
J Food Prot. 2020 Dec 15;:
Authors: Nyirabahizi E, Tyson GH, Tate H, Williams MS, Saini GS, Strain E
Abstract
As part of the National Antimicrobial Resistance Monitoring System (NARMS) activities, the United States Department of Agriculture (USDA) Food Safety Inspection Service (FSIS) collected cecal samples from food animal slaughter facilities throughout the country between 2014 and 2018. Of the 26,780 cecal samples from cattle, swine, chicken and turkey , 6,350 (23.71%) tested positive for Salmonella . NARMS tested Salmonella for susceptibility to aminoglycosides, folate pathway inhibitors, macrolides, phenicols, quinolones, beta lactams, and tetracyclines. Using the regional subdivisions defined in the USDA Office of Investigation, we used chi-square test to assess potential association between the region from which the samples were collected and both Salmonella prevalence and susceptibility. The results show a significant association between region and Salmonella prevalence, when accounting for source and establishment size, with the southeast region having the highest probability of finding Salmonella . However, the western region had the highest resistance probability across all antimicrobial classes except for macrolides, which showed no regional association. This association between region and resistance was strongest among isolates from cattle. Analysis of whole-genome sequencing data indicated that a significantly higher prevalence of Salmonella Newport in cattle in the western region (accounting for 9.52% of cattle isolates, compared to 3.44% in other regions) may account for the greater resistance to multiple drug classes. Approximately 90% of Salmonella Newport in the west exhibited the MDR-AmpC phenotype encoded by aph(3'')-Ib/aph(6)-Id , bla CMY-2 , floR , sul2 , and tetA. . Thus, differences in resistance across regions may be due to geographical differences in the prevalence of specific Salmonella serotypes and their accompanying resistance genes.
PMID: 33320944 [PubMed - as supplied by publisher]
Syndemic of Lifetime Mental Illness, Substance Use Disorders, and Trauma and Their Association With Adverse Perinatal Outcomes.
J Interpers Violence. 2020 01;35(1-2):476-495
Authors: McDonald LR, Antoine DG, Liao C, Lee A, Wahab M, Coleman JS
Abstract
Adverse perinatal outcomes are a significant contributor to neonatal and infant deaths. Mental illness, substance use disorders, and interpersonal trauma are often prevalent within obstetrical populations. Previous literature has documented the individual associations between these psychosocial factors and adverse perinatal outcomes. The co-occurrence of these three psychosocial factors might represent a syndemic among pregnant women, although they have not been described as such in the literature. Analysis of the interrelatedness and aggregate effect of these factors may allow for a more effective screening process that may reduce adverse perinatal outcomes. The objective of this article is to examine whether psychosocial factors (mental illness, substance use disorders, and interpersonal trauma) were independently and synergistically associated with adverse perinatal outcomes. This is a retrospective cohort study of 1,656 pregnant women at a single institution. Perinatal outcome and psychosocial data were abstracted from each participant's electronic medical record. Univariate and bivariate analyses, and multiple logistic regression were performed. Mean age was 27.5 (SD = 6.2) years. The majority was Black (60.6%) and single (58%). Psychosocial factors were reported in 35% of women. The incidence of adverse perinatal outcomes increased with greater number of psychosocial factors: 21.2% if no psychosocial factor, 27.0% if one psychosocial factor, 27.4% if two, and 35.3% if all three (for trend, p = .01). Women who reported all three psychosocial factors had twice the odds of adverse perinatal outcomes (adjusted odds ratio = 2.04, 95% confidence interval = [1.09, 3.81], p = .03) compared with those who reported none. Our data suggest there is a synergistic relationship between the psychosocial factors that is associated with increased adverse perinatal outcomes. A validated screening tool is needed to stratify patient's risk of adverse perinatal outcomes based on psychosocial factors. Such screening could lead to tailored interventions that could decrease adverse perinatal outcomes.
PMID: 29294630 [PubMed - indexed for MEDLINE]
Development and validation of language and visuospatial composite scores in ADNI.
Alzheimers Dement (N Y). 2020;6(1):e12072
Authors: Choi SE, Mukherjee S, Gibbons LE, Sanders RE, Jones RN, Tommet D, Mez J, Trittschuh EH, Saykin A, Lamar M, Rabin L, Foldi NS, Sikkes S, Jutten RJ, Grandoit E, Mac Donald C, Risacher S, Groot C, Ossenkoppele R, Alzheimer's Disease Neuroimaging Initiative, Crane PK
Abstract
Introduction: Composite scores may be useful to summarize overall language or visuospatial functioning in studies of older adults.
Methods: We used item response theory to derive composite measures for language (ADNI-Lan) and visuospatial functioning (ADNI-VS) from the cognitive battery administered in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We evaluated the scores among groups of people with normal cognition, mild cognitive impairment (MCI), and Alzheimer's disease (AD) in terms of responsiveness to change, association with imaging findings, and ability to differentiate between MCI participants who progressed to AD dementia and those who did not progress.
Results: ADNI-Lan and ADNI-VS were able to detect change over time and predict conversion from MCI to AD. They were associated with most of the pre-specified magnetic resonance imaging measures. ADNI-Lan had strong associations with a cerebrospinal fluid biomarker pattern.
Discussion: ADNI-Lan and ADNI-VS may be useful composites for language and visuospatial functioning in ADNI.
PMID: 33313380 [PubMed]
Occipital-Cervical Fusion and Ventral Decompression in the Surgical Management of Chiari-1 Malformation and Syringomyelia: Analysis of Data From the Park-Reeves Syringomyelia Research Consortium.
Neurosurgery. 2020 Dec 11;:
Authors: CreveCoeur TS, Yahanda AT, Maher CO, Johnson GW, Ackerman LL, Adelson PD, Ahmed R, Albert GW, Aldana PR, Alden TD, Anderson RCE, Baird L, Bauer DF, Bierbrauer KS, Brockmeyer DL, Chern JJ, Couture DE, Daniels DJ, Dauser RC, Durham SR, Ellenbogen RG, Eskandari R, Fuchs HE, George TM, Grant GA, Graupman PC, Greene S, Greenfield JP, Gross NL, Guillaume DJ, Haller G, Hankinson TC, Heuer GG, Iantosca M, Iskandar BJ, Jackson EM, Jea AH, Johnston JM, Keating RF, Kelly MP, Khan N, Krieger MD, Leonard JR, Mangano FT, Mapstone TB, McComb JG, Menezes AH, Muhlbauer M, Oakes WJ, Olavarria G, O'Neill BR, Park TS, Ragheb J, Selden NR, Shah MN, Shannon C, Shimony JS, Smith J, Smyth MD, Stone SSD, Strahle JM, Tamber MS, Torner JC, Tuite GF, Wait SD, Wellons JC, Whitehead WE, Limbrick DD
Abstract
BACKGROUND: Occipital-cervical fusion (OCF) and ventral decompression (VD) may be used in the treatment of pediatric Chiari-1 malformation (CM-1) with syringomyelia (SM) as adjuncts to posterior fossa decompression (PFD) for complex craniovertebral junction pathology.
OBJECTIVE: To examine factors influencing the use of OCF and OCF/VD in a multicenter cohort of pediatric CM-1 and SM subjects treated with PFD.
METHODS: The Park-Reeves Syringomyelia Research Consortium registry was used to examine 637 subjects with cerebellar tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and at least 1 yr of follow-up after their index PFD. Comparisons were made between subjects who received PFD alone and those with PFD + OCF or PFD + OCF/VD.
RESULTS: All 637 patients underwent PFD, 505 (79.2%) with and 132 (20.8%) without duraplasty. A total of 12 subjects went on to have OCF at some point in their management (PFD + OCF), whereas 4 had OCF and VD (PFD + OCF/VD). Of those with complete data, a history of platybasia (3/10, P = .011), Klippel-Feil (2/10, P = .015), and basilar invagination (3/12, P < .001) were increased within the OCF group, whereas only basilar invagination (1/4, P < .001) was increased in the OCF/VD group. Clivo-axial angle (CXA) was significantly lower for both OCF (128.8 ± 15.3°, P = .008) and OCF/VD (115.0 ± 11.6°, P = .025) groups when compared to PFD-only group (145.3 ± 12.7°). pB-C2 did not differ among groups.
CONCLUSION: Although PFD alone is adequate for treating the vast majority of CM-1/SM patients, OCF or OCF/VD may be occasionally utilized. Cranial base and spine pathologies and CXA may provide insight into the need for OCF and/or OCF/VD.
PMID: 33313928 [PubMed - as supplied by publisher]
Mitochondrial dysfunction in neurological disorders: Exploring mitochondrial transplantation.
NPJ Regen Med. 2020 Nov 23;5(1):22
Authors: Norat P, Soldozy S, Sokolowski JD, Gorick CM, Kumar JS, Chae Y, Yağmurlu K, Prada F, Walker M, Levitt MR, Price RJ, Tvrdik P, Kalani MYS
Abstract
Mitochondria are fundamental for metabolic homeostasis in all multicellular eukaryotes. In the nervous system, mitochondria-generated adenosine triphosphate (ATP) is required to establish appropriate electrochemical gradients and reliable synaptic transmission. Notably, several mitochondrial defects have been identified in central nervous system disorders. Membrane leakage and electrolyte imbalances, pro-apoptotic pathway activation, and mitophagy are among the mechanisms implicated in the pathogenesis of neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's disease, as well as ischemic stroke. In this review, we summarize mitochondrial pathways that contribute to disease progression. Further, we discuss pathological states that damaged mitochondria impose on normal nervous system processes and explore new therapeutic approaches to mitochondrial diseases.
PMID: 33298971 [PubMed]
Whole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects.
Sci Rep. 2020 Dec 09;10(1):21584
Authors: Williams MT, Sugimoto C, Regan SL, Pitzer EM, Fritz AL, Mascia AE, Sertorio M, Vatner RE, Perentesis JP, Vorhees CV
Abstract
Proton radiotherapy causes less off-target effects than X-rays but is not without effect. To reduce adverse effects of proton radiotherapy, a model of cognitive deficits from conventional proton exposure is needed. We developed a model emphasizing multiple cognitive outcomes. Adult male rats (10/group) received a single dose of 0, 11, 14, 17, or 20 Gy irradiation (the 20 Gy group was not used because 50% died). Rats were tested once/week for 5 weeks post-irradiation for activity, coordination, and startle. Cognitive assessment began 6-weeks post-irradiation with novel object recognition (NOR), egocentric learning, allocentric learning, reference memory, and proximal cue learning. Proton exposure had the largest effect on activity and prepulse inhibition of startle 1-week post-irradiation that dissipated each week. 6-weeks post-irradiation, there were no effects on NOR, however proton exposure impaired egocentric (Cincinnati water maze) and allocentric learning and caused reference memory deficits (Morris water maze), but did not affect proximal cue learning or swimming performance. Proton groups also had reduced striatal levels of the dopamine transporter, tyrosine hydroxylase, and the dopamine receptor D1, effects consistent with egocentric learning deficits. This new model will facilitate investigations of different proton dose rates and drugs to ameliorate the cognitive sequelae of proton radiotherapy.
PMID: 33299021 [PubMed - in process]
Quantifying neurologic disease using biosensor measurements in-clinic and in free-living settings in multiple sclerosis.
NPJ Digit Med. 2019 Dec 11;2(1):123
Authors: Chitnis T, Glanz BI, Gonzalez C, Healy BC, Saraceno TJ, Sattarnezhad N, Diaz-Cruz C, Polgar-Turcsanyi M, Tummala S, Bakshi R, Bajaj VS, Ben-Shimol D, Bikhchandani N, Blocker AW, Burkart J, Cendrillon R, Cusack MP, Demiralp E, Jooste SK, Kharbouch A, Lee AA, Lehár J, Liu M, Mahadevan S, Murphy M, Norton LC, Parlikar TA, Pathak A, Shoeb A, Soderberg E, Stephens P, Stoertz AH, Thng F, Tumkur K, Wang H, Rhodes J, Rudick RA, Ransohoff RM, Phillips GA, Bruzik E, Marks WJ, Weiner HL, Snyder TM
Abstract
Technological advances in passive digital phenotyping present the opportunity to quantify neurological diseases using new approaches that may complement clinical assessments. Here, we studied multiple sclerosis (MS) as a model neurological disease for investigating physiometric and environmental signals. The objective of this study was to assess the feasibility and correlation of wearable biosensors with traditional clinical measures of disability both in clinic and in free-living in MS patients. This is a single site observational cohort study conducted at an academic neurological center specializing in MS. A cohort of 25 MS patients with varying disability scores were recruited. Patients were monitored in clinic while wearing biosensors at nine body locations at three separate visits. Biosensor-derived features including aspects of gait (stance time, turn angle, mean turn velocity) and balance were collected, along with standardized disability scores assessed by a neurologist. Participants also wore up to three sensors on the wrist, ankle, and sternum for 8 weeks as they went about their daily lives. The primary outcomes were feasibility, adherence, as well as correlation of biosensor-derived metrics with traditional neurologist-assessed clinical measures of disability. We used machine-learning algorithms to extract multiple features of motion and dexterity and correlated these measures with more traditional measures of neurological disability, including the expanded disability status scale (EDSS) and the MS functional composite-4 (MSFC-4). In free-living, sleep measures were additionally collected. Twenty-three subjects completed the first two of three in-clinic study visits and the 8-week free-living biosensor period. Several biosensor-derived features significantly correlated with EDSS and MSFC-4 scores derived at visit two, including mobility stance time with MSFC-4 z-score (Spearman correlation -0.546; p = 0.0070), several aspects of turning including turn angle (0.437; p = 0.0372), and maximum angular velocity (0.653; p = 0.0007). Similar correlations were observed at subsequent clinic visits, and in the free-living setting. We also found other passively collected signals, including measures of sleep, that correlated with disease severity. These findings demonstrate the feasibility of applying passive biosensor measurement techniques to monitor disability in MS patients both in clinic and in the free-living setting.
PMID: 33299125 [PubMed]
