Pulmonary Sequestration Causing Severe Cardiac Failure Requiring Lobectomy in an Extreme Preterm Infant

We report a case of a large, extralobar pulmonary sequestration in a preterm infant born at 25 weeks gestational age. A computed tomography (CT) angiogram demonstrated that the arterial supply arose from the celiac trunk while an abnormally large, single left pulmonary vein drained the sequestration. This, along with the large patent ductus arteriosus (PDA), created a double left to right shunt, which resulted in severe, high output cardiac failure. Despite aggressive medical management for 3 weeks, he remained critically ill and developed renal failure. Therefore, after multiple, extensive multi-disciplinary discussions with the family, resection was offered as the only possibility for survival. He underwent a left thoracotomy and resection of the extra-lobar sequestration, which was occupying the lower two-thirds of his left hemithorax. To our knowledge, this is the youngest patient in the literature to undergo resection of an extra-lobar sequestration. Management challenges in terms of balancing the cardiac failure against the timing, approach and success of surgical intervention are also discussed along with a review of the literature

Estimation of GFR in Patients With Cystic Fibrosis: A Cross-Sectional Study

Background: Patients with cystic fibrosis (CF) have frequent infectious complications requiring nephrotoxic medications, necessitating monitoring of renal function. Although adult studies have suggested that cystatin C (CysC)-based estimated glomerular filtration rate (eGFR) may be preferable due to reduced muscle mass of patients with CF, pediatric patients remain understudied. Objective: Our objective was to determine which eGFR formula is best for estimating glomerular filtration rate (GFR) in pediatric patients with CF. Methods: A total of 17 patients with CF treated with nephrotoxic antibiotics were recruited from the Children’s Hospital at London Health Sciences Centre, London, Ontario, Canada. 99Tc DTPA GFR (measured GFR [mGFR]) was measured with 4-point measurements starting at 120 minutes using a 2-compartmental model with Brøchner-Mortensen correction, with simultaneous measurement of creatinine, urea, and CysC. The eGFR was calculated using 16 known equations based on creatinine, urea, CysC, or combinations of these. Primary outcome measures were correlation with mGFR, and agreement within 10% for various eGFR equations. Results: Mean mGFR was 136 ± 21 mL/min/1.73 m2. Mean creatinine, CysC, and urea were 38 ± 10 μmol/L, 0.72 ± 0.08 mg/L, and 3.9 ± 1.4 mmol/L, respectively. The 2014 Grubb CysC eGFR had the best correlation coefficient (r = 0.75, P =.0004); however, only 35% were within 10%. The new Schwartz formula with creatinine and urea had the best agreement within 10%, but a relatively low correlation coefficient (r = 0.63, P =.0065, 64% within 10%). Conclusions: Our study suggests that none of the eGFR formulae work well in this small cohort of pediatric patients with CF with preserved body composition, possibly due to inflammation causing false elevations of CysC. Based on the small numbers, we cannot conclude which eGFR formula is best

Cyclic AMP signaling in Dictyostelium promotes the translocation of the copine family of calcium-binding proteins to the plasma membrane

Abstract Background Copines are calcium-dependent phospholipid-binding proteins found in many eukaryotic organisms and are thought to be involved in signaling pathways that regulate a wide variety of cellular processes. Copines are characterized by having two C2 domains at the N-terminus accompanied by an A domain at the C-terminus. Six copine genes have been identified in the Dictyostelium genome, cpnA – cpnF. Results Independent cell lines expressing CpnA, CpnB, CpnC, CpnE, or CpnF tagged with green fluorescent protein (GFP) were created as tools to study copine protein membrane-binding and localization. In general, the GFP-tagged copine proteins appeared to localize to the cytoplasm in live cells. GFP-tagged CpnB, CpnC, and CpnF were also found in the nucleus. When cells were fixed or when live cells were treated with calcium ionophore, the GFP-tagged copine proteins were found associated with the plasma membrane and vesicular organelles. When starved Dictyostelium cells were stimulated with cAMP, which causes a transitory increase in calcium concentration, all of the copines translocated to the plasma membrane, but with varying magnitudes and on and off times, suggesting each of the copines has distinct calcium-sensitivities and/or membrane-binding properties. In vitro membrane binding assays showed that all of the GFP-tagged copines pelleted with cellular membranes in the presence of calcium; yet, each copine displayed distinct calcium-independent membrane-binding in the absence of calcium. A lipid overlay assay with purified GFP-tagged copine proteins was used to screen for specific phospholipid-binding targets. Similar to other proteins that contain C2 domains, GFP-tagged copines bound to a variety of acidic phospholipids. CpnA, CpnB, and CpnE bound strongly to PS, PI(4)P, and PI(4,5)P2, while CpnC and CpnF bound strongly to PI(4)P. Conclusions Our studies show that the Dictyostelium copines are soluble cytoplasmic and nuclear proteins that have the ability to bind intracellular membranes. Moreover, copines display different membrane-binding properties suggesting they play distinct roles in the cell. The transient translocation of copines to the plasma membrane in response to cAMP suggests copines may play a specific role in chemotaxis signaling.https://deepblue.lib.umich.edu/bitstream/2027.42/145158/1/12860_2018_Article_160.pd

Cyclic AMP signaling in Dictyostelium promotes the translocation of the copine family of calcium-binding proteins to the plasma membrane

Abstract Background Copines are calcium-dependent phospholipid-binding proteins found in many eukaryotic organisms and are thought to be involved in signaling pathways that regulate a wide variety of cellular processes. Copines are characterized by having two C2 domains at the N-terminus accompanied by an A domain at the C-terminus. Six copine genes have been identified in the Dictyostelium genome, cpnA – cpnF. Results Independent cell lines expressing CpnA, CpnB, CpnC, CpnE, or CpnF tagged with green fluorescent protein (GFP) were created as tools to study copine protein membrane-binding and localization. In general, the GFP-tagged copine proteins appeared to localize to the cytoplasm in live cells. GFP-tagged CpnB, CpnC, and CpnF were also found in the nucleus. When cells were fixed or when live cells were treated with calcium ionophore, the GFP-tagged copine proteins were found associated with the plasma membrane and vesicular organelles. When starved Dictyostelium cells were stimulated with cAMP, which causes a transitory increase in calcium concentration, all of the copines translocated to the plasma membrane, but with varying magnitudes and on and off times, suggesting each of the copines has distinct calcium-sensitivities and/or membrane-binding properties. In vitro membrane binding assays showed that all of the GFP-tagged copines pelleted with cellular membranes in the presence of calcium; yet, each copine displayed distinct calcium-independent membrane-binding in the absence of calcium. A lipid overlay assay with purified GFP-tagged copine proteins was used to screen for specific phospholipid-binding targets. Similar to other proteins that contain C2 domains, GFP-tagged copines bound to a variety of acidic phospholipids. CpnA, CpnB, and CpnE bound strongly to PS, PI(4)P, and PI(4,5)P2, while CpnC and CpnF bound strongly to PI(4)P. Conclusions Our studies show that the Dictyostelium copines are soluble cytoplasmic and nuclear proteins that have the ability to bind intracellular membranes. Moreover, copines display different membrane-binding properties suggesting they play distinct roles in the cell. The transient translocation of copines to the plasma membrane in response to cAMP suggests copines may play a specific role in chemotaxis signaling.https://deepblue.lib.umich.edu/bitstream/2027.42/145158/1/12860_2018_Article_160.pd

Beyond the Bandwagon: Curating Cultural Memory at Milner Library

Archival and manuscript materials record human experience; they document how people have lived, worked, interacted, and thought about the world. These unique or rare materials make visible the experience and impact of individuals and organizations within their respective cultural, geographical, historical, local, and educational milieu. By exploring such documents and objects, patrons can see and investigate these relationships firsthand. Primary sources form the bedrock of humanistic research, personal inquiry, and engaged teaching. With this volume, we invite you to explore the unique and rare materials housed in Milner Library’s Special Collections and Dr. Jo Ann Rayfield University Archives as well as the services that bring them to life for readers worldwide. Contributed essays from scholars and collection stewards highlight how a small sample of these rich collections facilitate teaching and learning within the Illinois State University community and beyond.https://ir.library.illinoisstate.edu/mlp/1032/thumbnail.jp

Pediatric home mechanical ventilation: A Canadian Thoracic Society clinical practice guideline executive summary

Over the last 30 to 40 years, improvements in technology, as well as changing clinical practice regarding the appropriateness of long-term ventilation in patients with “non-curable” disorders, have resulted in increasing numbers of children surviving what were previously considered fatal conditions. This has come but at the expense of requiring ongoing, long-term prolonged mechanical ventilation (both invasive and noninvasive). Although there are many publications pertaining to specific aspects of home mechanical ventilation (HMV) in children, there are few comprehensive guidelines that bring together all of the current literature. In 2011 the Canadian Thoracic Society HMV Guideline Committee published a review of the available English literature on topics related to HMV in adults, and completed a detailed guideline that will help standardize and improve the assessment and management of individuals requiring noninvasive or invasive HMV. This current document is intended to be a companion to the 2011 guidelines, concentrating on the issues that are either unique to children on HMV (individuals under 18 years of age), or where common pediatric practice diverges significantly from that employed in adults on long-term home ventilation. As with the adult guidelines,1 this document provides a disease-specific review of illnesses associated with the necessity for long-term ventilation in children, including children with chronic lung disease, spinal muscle atrophy, muscular dystrophies, kyphoscoliosis, obesity hypoventilation syndrome, and central hypoventilation syndromes. It also covers important common themes such as airway clearance, the ethics of initiation of long-term ventilation in individuals unable to give consent, the process of transition to home and to adult centers, and the impact, both financial, as well as social, that this may have on the child\u27s families and caregivers. The guidelines have been extensively reviewed by international experts, allied health professionals and target audiences. They will be updated on a regular basis to incorporate any new information

Meta-barcoded evaluation of the ISO standard 11063 DNA extraction procedure to characterize soil bacterial and fungal community diversity and composition

This study was designed to assess the influence of three soil DNA extraction procedures, namely the International Organization for Standardization (ISO-11063, GnS-GII and modified ISO procedure (ISOm), on the taxonomic diversity and composition of soil bacterial and fungal communities. The efficacy of each soil DNA extraction method was assessed on five soils, differing in their physico-chemical characteristics and land use. A meta-barcoded pyrosequencing approach targeting 16S and 18S rRNA genes was applied to characterize soil microbial communities. We first observed that the GnS-GII introduced some heterogeneity in bacterial composition between replicates. Then, although no major difference was observed between extraction procedures for soil bacterial diversity, we saw that the number of fungal genera could be underestimated by the ISO-11063. In particular, this procedure underestimated the detection in several soils of the genera Cryptococcus, Pseudallescheria, Hypocrea and Plectosphaerella, which are of ecological interest. Based on these results, we recommend using the ISOm method for studies focusing on both the bacterial and fungal communities. Indeed, the ISOm procedure provides a better evaluation of bacterial and fungal communities and is limited to the modification of the mechanical lysis step of the existing ISO-11063 standard

Psychosocial Response to Uncertain Newborn Screening Results for Cystic Fibrosis

Objective To explore the psychosocial implications of diagnostic uncertainty that result from inconclusive results generated by newborn bloodspot screening (NBS) for cystic fibrosis (CF). Study design Using a mixed methods prospective cohort study of children who received NBS for CF, we compared psychosocial outcomes of parents whose children who received persistently inconclusive results with those whose children received true positive or screen-negative results. Results Mothers of infants who received inconclusive results (n = 17), diagnoses of CF (n = 15), and screen-negative results (n = 411) were surveyed; 23 parent interviews were completed. Compared with mothers of infants with true positive/screen-negative results, mothers of infants with inconclusive results reported greater perceived uncertainty (P .05). Qualitatively, parents valued being connected to experts but struggled with the meaning of an uncertain diagnosis, worried about their infant's health-related vulnerability, and had mixed views about surveillance. Conclusion Inconclusive CF NBS results were not associated with anxiety or vulnerability but led to health-related uncertainty and qualitative concerns. Findings should be considered alongside efforts to optimize protocols for CF screening and surveillance. Educational and psychosocial supports are warranted for these families.Peer reviewe

Immunoreactive trypsinogen levels in newborn screened infants with an inconclusive diagnosis of cystic fibrosis.

BACKGROUND: Newborn screening (NBS) for cystic fibrosis (CF) not only identifies infants with a diagnosis of CF, but also those with an uncertain diagnosis of cystic fibrosis (CF), i.e. CF transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS) or CF screen positive inconclusive diagnosis (CFSPID). These infants have an uncertain long-term outcome and it is currently unclear around time of diagnosis, which infants are at higher risk of later fulfilling a CF diagnosis. In this study, we hypothesised that immunoreactive trypsinogen (IRT) levels, used in NBS as a marker of pancreatic disease and function, may reflect the degree of CFTR dysfunction in each individual and therefore would help to identify those with CRMS/CSPID who are later at risk for meeting the criteria of CF. METHODS: In this longitudinal, prospective study, infants with CRMS/CFSPID and CF were recruited and followed in 9 CF clinics (Canada and Italy). We compared NBS IRT levels between CF and CRMS/CFSPID, and between children with CRMS/CFSPID→CF and CRMS/CFSPID→CRMS/CFSPID during the period of June 2007 to April 2016. RESULTS: Ninety eight CRMS/CFSPID and 120 CF subjects were enrolled. During the study period, 14 (14.3%) CRMS/CFSPID subjects fulfilled the diagnostic criteria for CF (CRMS/CFSPID→CF), while the diagnosis remained uncertain (CRMS/CFSPID→ CRMS/CFSPID) in 84 (85.7%) subjects. Significantly higher NBS IRT concentrations (ng/ml) were present in CF than CRMS/CFPSID (median (interquartile range): 143.8 (99.8-206.2) vs. 75.0 (61.0-105.9); P \u3c 0.0001). Infants with CRMS/CFSPID→CF (n = 14) had significantly higher NBS IRT concentrations (ng/ml) than CRMS/CFSPID→ CRMS/CFSPID (n = 83) (median (interquartile range): 108.9 (72.3-126.8) vs. 73.7(60.0-96.0); P = 0.02). CONCLUSIONS: Amongst infants who tested positive on NBS for CF, there is a gradation of elevated NBS IRT concentrations. Infants with CF have higher NBS IRT levels than CRMS/CFPSID, and higher NBS IRT concentrations were present in infants with CRMS/CFSPID→CF than CRMS/CFSPID→ CRMS/CFSPID. NBS IRT concentrations, in concert with other factors, may have the potential to predict the likelihood of CF amongst infants with CRMS/CFSPID