MR diffusion changes in the perimeter of the lateral ventricles demonstrate periventricular injury in post-hemorrhagic hydrocephalus of prematurity

OBJECTIVES: Injury to the preterm lateral ventricular perimeter (LVP), which contains the neural stem cells responsible for brain development, may contribute to the neurological sequelae of intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus of prematurity (PHH). This study utilizes diffusion MRI (dMRI) to characterize the microstructural effects of IVH/PHH on the LVP and segmented frontal-occipital horn perimeters (FOHP). STUDY DESIGN: Prospective study of 56 full-term infants, 72 very preterm infants without brain injury (VPT), 17 VPT infants with high-grade IVH without hydrocephalus (HG-IVH), and 13 VPT infants with PHH who underwent dMRI at term equivalent. LVP and FOHP dMRI measures and ventricular size-dMRI correlations were assessed. RESULTS: In the LVP, PHH had consistently lower FA and higher MD and RD than FT and VPT (p\u3c.050). However, while PHH FA was lower, and PHH RD was higher than their respective HG-IVH measures (p\u3c.050), the MD and AD values did not differ. In the FOHP, PHH infants had lower FA and higher RD than FT and VPT (p\u3c.010), and a lower FA than the HG-IVH group (p\u3c.001). While the magnitude of AD in both the LVP and FOHP were consistently less in the PHH group on pairwise comparisons to the other groups, the differences were not significant (p\u3e.050). Ventricular size correlated negatively with FA, and positively with MD and RD (p\u3c.001) in both the LVP and FOHP. In the PHH group, FA was lower in the FOHP than in the LVP, which was contrary to the observed findings in the healthy infants (p\u3c.001). Nevertheless, there were no regional differences in AD, MD, and RD in the PHH group. CONCLUSION: HG-IVH and PHH results in aberrant LVP/FOHP microstructure, with prominent abnormalities among the PHH group, most notably in the FOHP. Larger ventricular size was associated with greater magnitude of abnormality. LVP/FOHP dMRI measures may provide valuable biomarkers for future studies directed at improving the management and neurological outcomes of IVH/PHH

Dynamic responses of B acteroides thetaiotaomicron during growth on glycan mixtures

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98163/1/mmi12228-sup-0001-si.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98163/2/mmi12228.pd

Expression Levels of a Kinesin-13 Microtubule Depolymerase Modulates the Effectiveness of Anti-Microtubule Agents

Chemotherapeutic drugs often target the microtubule cytoskeleton as a means to disrupt cancer cell mitosis and proliferation. Anti-microtubule drugs inhibit microtubule dynamics, thereby triggering apoptosis when dividing cells activate the mitotic checkpoint. Microtubule dynamics are regulated by microtubule-associated proteins (MAPs); however, we lack a comprehensive understanding about how anti-microtubule agents functionally interact with MAPs. In this report, we test the hypothesis that the cellular levels of microtubule depolymerases, in this case kinesin-13 s, modulate the effectiveness of the microtubule disrupting drug colchicine.We used a combination of RNA interference (RNAi), high-throughput microscopy, and time-lapse video microscopy in Drosophila S2 cells to identify a specific MAP, kinesin-like protein 10A (KLP10A), that contributes to the efficacy of the anti-microtubule drug colchicine. KLP10A is an essential microtubule depolymerase throughout the cell cycle. We find that depletion of KLP10A in S2 cells confers resistance to colchicine-induced microtubule depolymerization to a much greater extent than depletion of several other destabilizing MAPs. Using image-based assays, we determined that control cells retained 58% (+/-2%SEM) of microtubule polymer when after treatment with 2 microM colchicine for 1 hour, while cells depleted of KLP10A by RNAi retained 74% (+/-1%SEM). Likewise, overexpression of KLP10A-GFP results in increased susceptibility to microtubule depolymerization by colchicine.Our results demonstrate that the efficacy of microtubule destabilization by a pharmacological agent is dependent upon the cellular expression of a microtubule depolymerase. These findings suggest that expression levels of Kif2A, the human kinesin-13 family member, may be an attractive biomarker to assess the effectiveness of anti-microtubule chemotherapies. Knowledge of how MAP expression levels affect the action of anti-microtubule drugs may prove useful for evaluating possible modes of cancer treatment

Functional Modeling Identifies Paralogous Solanesyl-diphosphate Synthases That Assemble the Side Chain of Plastoquinone-9 in Plastids

Background: Plastid isoforms of solanesyl-diphosphate synthase catalyze the elongation of the prenyl side chain of plastoquinone-9. Results: Corresponding mutants display lower levels of plastoquinone-9 and plastochromanol-8 and display intact levels of vitamin E. Conclusion: Plastochromanol-8 originates from a subfraction of non-photoactive plastoquinol-9 and is not essential for seed longevity. Significance: Viable plastoquinone-9 mutants are invaluable tools for understanding plastid metabolism

Occult Pneumothoraces in Children With Blunt Torso Trauma

Objectives Plain chest x‐ray (CXR) is often the initial screening test to identify pneumothoraces in trauma patients. Computed tomography (CT) scans can identify pneumothoraces not seen on CXR (“occult pneumothoraces”), but the clinical importance of these radiographically occult pneumothoraces in children is not well understood. The objectives of this study were to determine the proportion of occult pneumothoraces in injured children and the rate of treatment with tube thoracostomy among these children. Methods This was a planned substudy from a large prospective multicenter observational cohort study of children younger than 18 years old evaluated in emergency departments (EDs) in the Pediatric Emergency Care Applied Research Network (PECARN) for blunt torso trauma from May 2007 to January 2010. Children with CXRs as part of their trauma evaluations were included for analysis. The faculty radiologist interpretations of the CXRs and any subsequent imaging studies, including CT scans, were reviewed for the absence or presence of pneumothoraces. An “occult pneumothorax” was defined as a pneumothorax that was not identified on CXR, but was subsequently demonstrated on cervical, chest, or abdominal CT scan. Rates of pneumothoraces and placement of tube thoracostomies and rate differences with 95% confidence intervals (CIs) were calculated. Results Of 12,044 enrolled in the parent study, 8,020 (67%) children (median age = 11.3 years, interquartile range [IQR] = 5.3 to 15.2 years) underwent CXRs in the ED, and these children make up the study population. Among these children, 4,276 had abdominal CT scans performed within 24 hours. A total of 372 of 8,020 children (4.6%; 95% CI = 4.2% to 5.1%) had pneumothoraces identified by CXR and/or CT. The CXRs visualized pneumothoraces in 148 patients (1.8%; 95% CI = 1.6% to 2.2%), including one false‐positive pneumothorax, which was identified on CXR, but was not demonstrated on CT. Occult pneumothoraces were present in 224 of 372 (60.2%; 95% CI = 55.0% to 65.2%) children with pneumothoraces. Tube thoracostomies were performed in 85 of 148 (57.4%; 95% CI = 49.0% to 65.5%) children with pneumothoraces on CXR and in 35 of 224 (15.6%; 95% CI = 11.1% to 21.1%) children with occult pneumothoraces (rate difference = –41.8%; 95% CI = –50.8 to –32.3%). Conclusions In pediatric patients with blunt torso trauma, pneumothoraces are uncommon, and most are not identified on the ED CXR. Nearly half of pneumothoraces, and most occult pneumothoraces, are managed without tube thoracostomy. Observation, including in children requiring endotracheal intubation, should be strongly considered during the initial management of children with occult pneumothoraces. Resumen Objetivos La radiografía de tórax simple (RXT) es a menudo la prueba de despistaje inicial para identificar los neumotórax en los pacientes con traumatismo. La tomografía computarizada (TC) puede identificar neumotórax no vistos en la RXT (“neumotórax ocultos”), aunque la importancia clínica de estos neumotórax radiográficamente ocultos en los niños no está muy estudiada. Los objetivos de este estudio fueron determinar la proporción de neumotórax ocultos en los niños accidentados y el porcentaje de tratamiento con tubo de toracostomía en estos niños. Metodología Subestudio diseñado a partir de un gran estudio observacional de cohorte prospectivo multicéntrico de niños menores de 18 años atendidos en los servicios de urgencias (SU) de la Pediatric Emergency Care Applied Research Network (PECARN) que habían sido evaluados por traumatismo torácico cerrado de mayo de 2007 a enero de 2010. Se incluyeron en el análisis los niños en los que la RXT fue parte de la evaluación inicial del traumatismo. Las interpretaciones del radiólogo de las RXT y de cualquier estudio de imagen posterior, incluyendo a TC, se revisaron para la ausencia o presencia de neumotórax. Se definió “neumotórax oculto” como un neumotórax que no fue identificado en la RXT pero que fue posteriormente visualizado en la TC abdominal, torócica o cervical. Se calcularon los porcentajes de neumotórax e inserción de tubo de toracostomía y las diferencias de sus porcentajes con los intervalos de confianza (IC) al 95%. Resultados De los 12.044 incluidos en el estudio principal, se llevo a cabo una RXT en el SU en 8.020 (67%) niños (mediana de edad 11,3 años, rango intercuartílico 5,3 a 15,2), que constituyeron la población de estudio. De estos niños, 4.276 tuvieron una TC realizada en las primeras 24 horas. En 372 de los 8.020 niños (4,6%; IC 95% = 4,2% a 5,1%) se identificó un neumotórax en la RXT y/o la TC. La RXT mostró neumotórax en 148 pacientes (1,8%; IC 95% = 1,6% a 2,2%), incluyendo un falso positivo de neumotórax, que fue identificado en la RXT pero que no fue demostrado en la TC. Los neumotórax ocultos estuvieron presentes en 224 de los 372 niños con neumotórax (60,2%; IC 95% = 55,0% a 65,2%). Se insertaron tubos de toracostomía en 85 de los 148 niños con neumotórax en la RXT (57,4%; IC 95% = 49,0% a 65,5%), y en 35 de los 224 niños con neumotórax oculto (15,6%; IC 95% = 11,1% a 21,1%; diferencia de porcentajes ‐41,8%; IC 95% = ‐50,8 a ‐32,3%). Conclusiones En los pacientes pediátricos con traumatismo torácico cerrado, los neumotórax son poco frecuentes, y la mayoría no son identificados en la RXT en el SU. Casi la mitad de los neumotórax, y la mayoría de los neumotórax ocultos son manejados sin tubo de toracostomía. La observación, incluyendo en los niños que requieren intubación endotraqueal, debería ser especialmente considerada durante el manejo inicial de los niños con neumotórax ocultos.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106913/1/acem12344.pd

Mask wearing in community settings reduces SARS-CoV-2 transmission

The effectiveness of mask wearing at controlling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been unclear. While masks are known to substantially reduce disease transmission in healthcare settings [D. K. Chu et al., Lancet 395, 1973–1987 (2020); J. Howard et al., Proc. Natl. Acad. Sci. U.S.A. 118, e2014564118 (2021); Y. Cheng et al., Science eabg6296 (2021)], studies in community settings report inconsistent results [H. M. Ollila et al., medRxiv (2020); J. Brainard et al., Eurosurveillance 25, 2000725 (2020); T. Jefferson et al., Cochrane Database Syst. Rev. 11, CD006207 (2020)]. Most such studies focus on how masks impact transmission, by analyzing how effective government mask mandates are. However, we find that widespread voluntary mask wearing, and other data limitations, make mandate effectiveness a poor proxy for mask-wearing effectiveness. We directly analyze the effect of mask wearing on SARS-CoV-2 transmission, drawing on several datasets covering 92 regions on six continents, including the largest survey of wearing behavior ([Formula: see text] 20 million) [F. Kreuter et al., https://gisumd.github.io/COVID-19-API-Documentation (2020)]. Using a Bayesian hierarchical model, we estimate the effect of mask wearing on transmission, by linking reported wearing levels to reported cases in each region, while adjusting for mobility and nonpharmaceutical interventions (NPIs), such as bans on large gatherings. Our estimates imply that the mean observed level of mask wearing corresponds to a 19% decrease in the reproduction number R. We also assess the robustness of our results in 60 tests spanning 20 sensitivity analyses. In light of these results, policy makers can effectively reduce transmission by intervening to increase mask wearing

Radiation-free CMR diagnostic heart catheterization in children.

BACKGROUND: Children with heart disease may require repeated X-Ray cardiac catheterization procedures, are more radiosensitive, and more likely to survive to experience oncologic risks of medical radiation. Cardiovascular magnetic resonance (CMR) is radiation-free and offers information about structure, function, and perfusion but not hemodynamics. We intend to perform complete radiation-free diagnostic right heart catheterization entirely using CMR fluoroscopy guidance in an unselected cohort of pediatric patients; we report the feasibility and safety. METHODS: We performed 50 CMR fluoroscopy guided comprehensive transfemoral right heart catheterizations in 39 pediatric (12.7 ± 4.7 years) subjects referred for clinically indicated cardiac catheterization. CMR guided catheterizations were assessed by completion (success/failure), procedure time, and safety events (catheterization, anesthesia). Pre and post CMR body temperature was recorded. Concurrent invasive hemodynamic and diagnostic CMR data were collected. RESULTS: During a twenty-two month period (3/2015 - 12/2016), enrolled subjects had the following clinical indications: post-heart transplant 33%, shunt 28%, pulmonary hypertension 18%, cardiomyopathy 15%, valvular heart disease 3%, and other 3%. Radiation-free CMR guided right heart catheterization attempts were all successful using passive catheters. In two subjects with septal defects, right and left heart catheterization were performed. There were no complications. One subject had six such procedures. Most subjects (51%) had undergone multiple (5.5 ± 5) previous X-Ray cardiac catheterizations. Retained thoracic surgical or transcatheter implants (36%) did not preclude successful CMR fluoroscopy heart catheterization. During the procedure, two subjects were receiving vasopressor infusions at baseline because of poor cardiac function, and in ten procedures, multiple hemodynamic conditions were tested. CONCLUSIONS: Comprehensive CMR fluoroscopy guided right heart catheterization was feasible and safe in this small cohort of pediatric subjects. This includes subjects with previous metallic implants, those requiring continuous vasopressor medication infusions, and those requiring pharmacologic provocation. Children requiring multiple, serial X-Ray cardiac catheterizations may benefit most from radiation sparing. This is a step toward wholly CMR guided diagnostic (right and left heart) cardiac catheterization and future CMR guided cardiac intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT02739087 registered February 17, 2016