Publications by authors named "T J Wood"

1,889 Publications

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Diffusion Tensor Imaging Changes Do Not Affect Long-Term Neurodevelopment following Early Erythropoietin among Extremely Preterm Infants in the Preterm Erythropoietin Neuroprotection Trial.

Brain Sci 2021 Oct 16;11(10). Epub 2021 Oct 16.

Division of Neonatology, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.

We aimed to evaluate diffusion tensor imaging (DTI) in infants born extremely preterm, to determine the effect of erythropoietin (Epo) on DTI, and to correlate DTI with neurodevelopmental outcomes at 2 years of age for infants in the Preterm Erythropoietin Neuroprotection (PENUT) Trial. Infants who underwent MRI with DTI at 36 weeks postmenstrual age were included. Neurodevelopmental outcomes were evaluated by Bayley Scales of Infant and Toddler Development (BSID-III). Generalized linear models were used to assess the association between DTI parameters and treatment group, and then with neurodevelopmental outcomes. A total of 101 placebo- and 93 Epo-treated infants underwent MRI. DTI white matter mean diffusivity (MD) was lower in placebo- compared to Epo-treated infants in the cingulate and occipital regions, and occipital white matter fractional isotropy (FA) was lower in infants born at 24-25 weeks vs. 26-27 weeks. These values were not associated with lower BSID-III scores. Certain decreases in clustering coefficients tended to have lower BSID-III scores. Consistent with the PENUT Trial findings, there was no effect on long-term neurodevelopment in Epo-treated infants even in the presence of microstructural changes identified by DTI.
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http://dx.doi.org/10.3390/brainsci11101360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533828PMC
October 2021

Escherichia coli cryptic prophages sense nutrients to influence persister cell resuscitation.

Environ Microbiol 2021 Oct 19. Epub 2021 Oct 19.

Department of Chemical Engineering, Pennsylvania State University, University Park, Pennsylvania, 16802-4400, USA.

Cryptic prophages are not genomic junk but instead enable cells to combat myriad stresses as an active stress response. How these phage fossils affect persister cell resuscitation has, however, not been explored. Persister cells form as a result of stresses such as starvation, antibiotics and oxidative conditions, and resuscitation of these persister cells likely causes recurring infections such as those associated with tuberculosis, cystic fibrosis and Lyme disease. Deletion of each of the nine Escherichia coli cryptic prophages has no effect on persister cell formation. Strikingly, elimination of each cryptic prophage results in an increase in persister cell resuscitation with a dramatic increase in resuscitation upon deleting all nine prophages. This increased resuscitation includes eliminating the need for a carbon source and is due to activation of the phosphate import system resulting from inactivating the transcriptional regulator AlpA of the CP4-57 cryptic prophage. Deletion of alpA increases persister resuscitation, and AlpA represses phosphate regulator PhoR. Both phosphate regulators PhoP and PhoB stimulate resuscitation. This suggests a novel cellular stress mechanism controlled by cryptic prophages: regulation of phosphate uptake which controls the exit of the cell from dormancy and prevents premature resuscitation in the absence of nutrients.
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http://dx.doi.org/10.1111/1462-2920.15816DOI Listing
October 2021

3-Methylglutaconic aciduria in carriers of primary carnitine deficiency.

Eur J Med Genet 2021 Oct 9;64(12):104365. Epub 2021 Oct 9.

Greenwood Genetic Center, Greenwood, SC, USA; Divsion of Genetics, Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA.

The etiology of secondary 3-methylglutaconic aciduria (3-MGA-uria) is not well understood although is thought to be a marker of mitochondrial dysfunction. For this reason, suspicion for a secondary 3-MGA-uria often leads to an extensive clinical and laboratory work-up for mitochondrial disease, although in many cases evidence for mitochondrial dysfunction is never found. 3-methylglutaconic aciduria in healthy individuals without known metabolic disease has not been well described. Here, we describe clinical and biochemical features of 23 individuals evaluated at the Greenwood Genetic Center for low plasma free carnitine reported on newborn screening. Of the 23 individuals evaluated, four individuals were diagnosed with primary carnitine deficiency, 16 were identified as carriers for primary carnitine deficiency, and three individuals were determined to be unaffected non-carriers based on molecular and biochemical testing. Elevated 3-MGA (>20 mmol/mol of creatinine) was identified in nine carriers of primary carnitine deficiency, while all unaffected non carriers and all affected individuals with primary carnitine deficiency had a normal 3-MGA level (<20 mmol/mol of creatinine). Average 3-MGA among all carriers was 39.66 mmol/mol of creatinine. Average plasma free carnitine in among all carriers (n = 16) was 13.87 μm/L, and average plasma free carnitine was not significantly different between carriers with and those without elevated 3-MGA (p = 0.66). In summary, we describe elevated 3-MGA as a discriminatory feature in nine healthy carriers of primary carnitine deficiency. Our findings suggest that heterozygosity for pathogenic alterations on SLC22A5 should be considered in the differential for individuals with persistent 3-MGA-uria of unclear etiology.
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http://dx.doi.org/10.1016/j.ejmg.2021.104365DOI Listing
October 2021

Are Functional Outcomes of a Total Hip Arthroplasty Predictive of a Contralateral Total Hip Arthroplasty: A Retrospective Cohort Study.

J Arthroplasty 2021 Oct 8. Epub 2021 Oct 8.

Division of Orthopaedic Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada.

Background: Current literature suggests that 8%-35% of patients undergoing total hip arthroplasty (THA) undergo a subsequent contralateral THA. This study aims to determine if functional outcomes after primary THA predict outcomes in the subsequent primary THA of the contralateral side.

Methods: A retrospective cohort of patients undergoing staged bilateral primary THA was reviewed. The Oxford Hip Score (OHS) was utilized as the functional outcome measurement tool and was assessed preoperatively and at one year postoperatively. The minimal clinically important difference (MCID) was assessed. Based on the first-side THA one-year outcomes, the odds of maintaining an MCID, or not, for the second-side THA were determined.

Results: The study cohort consisted of 551 patients and 1102 primary THAs. The average postoperative OHSs were similar after the first and second THA. Patients achieving the MCID with the first-side surgery were 2.6 times (95% confidence interval 1.0 to 6.64, P = .04) more likely to achieve the MCID for the second-side surgery than patients failing to reach the MCID for their first-side surgery. After the first THA, 29 (5.3%) patients failed to reach the predefined MCID for the OHS compared with 54 (9.8%) patients undergoing their second THA (odds ratio: 1.96 [95% confidence interval: 1.23 to 3.1], χ = 8.14, P = .005).

Conclusions: Functional outcomes after the first THA are predictive of functional outcomes of the second THA. Patients are more likely to achieve a clinically significant improvement after their first THA related to higher preoperative OHSs before the second THA.
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http://dx.doi.org/10.1016/j.arth.2021.09.024DOI Listing
October 2021

Early Biomarkers of Hypoxia and Inflammation and Two-Year Neurodevelopmental Outcomes in the Preterm Erythropoietin Neuroprotection (PENUT) Trial.

EBioMedicine 2021 Oct 4;72:103605. Epub 2021 Oct 4.

Division of Neonatology, Department of Pediatrics, University of Washington, Seattle, WA. Electronic address:

Background: In the Preterm Erythropoietin (Epo) NeUroproTection (PENUT) Trial, potential biomarkers of neurological injury were measured to determine their association with outcomes at two years of age and whether Epo treatment decreased markers of inflammation in extremely preterm (<28 weeks' gestation) infants.

Methods: Plasma Epo was measured (n=391 Epo, n=384 placebo) within 24h after birth (baseline), 30min after study drug administration (day 7), 30min before study drug (day 9), and on day 14. A subset of infants (n=113 Epo, n=107 placebo) had interferon-gamma (IFN-γ), Interleukin (IL)-6, IL-8, IL-10, Tau, and tumour necrosis factor-α (TNF-α) levels evaluated at baseline, day 7 and 14. Infants were then evaluated at 2 years using the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III).

Findings: Elevated baseline Epo was associated with increased risk of death or severe disability (BSID-III Motor and Cognitive subscales <70 or severe cerebral palsy). No difference in other biomarkers were seen between treatment groups at any time, though Epo appeared to mitigate the association between elevated baseline IL-6 and lower BSID-III scores in survivors. Elevated baseline, day 7 and 14 Tau concentrations were associated with worse BSID-III Cognitive, Motor, and Language skills at two years.

Interpretation: Elevated Epo at baseline and elevated Tau in the first two weeks after birth predict poor outcomes in infants born extremely preterm. However, no clear prognostic cut-off values are apparent, and further work is required before these biomarkers can be widely implemented in clinical practice.

Funding: PENUT was funded by the National Institute of Neurological Disorders and Stroke (U01NS077955 and U01NS077953).
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http://dx.doi.org/10.1016/j.ebiom.2021.103605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498235PMC
October 2021
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