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Acylglycerol kinase (AGK) is a mitochondrial lipid kinase that contributes to protein biogenesis as a subunit of the TIM22 complex at the inner mitochondrial membrane. Mutations in AGK cause Sengers syndrome, an autosomal recessive condition characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, and lactic acidosis. We mapped the proteomic changes in Sengers patient fibroblasts and AGKKO cell lines to understand the effects of AGK dysfunction on mitochondria. This uncovered down-regulation of a number of proteins at the inner mitochondrial membrane, including many SLC25 carrier family proteins, which are predicted substrates of the complex. We also observed down-regulation of SFXN proteins, which contain five transmembrane domains, and show that they represent a novel class of TIM22 complex substrate. Perturbed biogenesis of SFXN proteins in cells lacking AGK reduces the proliferative capabilities of these cells in the absence of exogenous serine, suggesting that dysregulation of one-carbon metabolism is a molecular feature in the biology of Sengers syndrome.

Background Cystic echinococcosis (CE) is a zoonotic neglected tropical disease (zNTD) which imposes considerable financial burden to endemic countries. The 2021–2030 World Health Organization’s roadmap on NTDs has proposed that intensified control be achieved in hyperendemic areas of 17 countries by 2030. Successful interventions for disease control, and the scale-up of programmes applying such interventions, rely on understanding the associated costs and relative return for investment. We conducted a scoping review of existing peer-reviewed literature on economic evaluations of CE control strategies focused on Echinococcus granulosus zoonotic hosts. Methodology/Principal findings Database searches of Scopus, PubMed, Web of Science, CABI Direct and JSTOR were conducted and comprehensively reviewed in March 2022, using predefined search criteria with no date, field or language restrictions. A total of 100 papers were initially identified and assessed for eligibility against strict inclusion and exclusion criteria, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Bibliography review of included manuscripts was used to identify additional literature. Full review of the final manuscript selection (n = 9) was performed and cost data for control interventions were extracted. Conclusions/Significance There are very little published data pertaining to the cost and cost effectiveness of CE control interventions targeting its zoonotic hosts. Data given for costs are often incomplete, thus we were unable to perform an economic analysis and cost effectiveness study, highlighting a pressing need for this information. There is much scope for future work in this area. More detailed information and disaggregated costings need to be collected and made available. This would increase the accuracy of any cost-effective analyses to be performed and allow for a greater understanding of the opportunity cost of healthcare decisions and resource allocation by stakeholders and policy makers for effective and cost-effective CE control.

Overall, approximately one‐quarter of patients with genetic eye diseases will receive a molecular diagnosis. Patients with developmental eye disorders face a number of diagnostic challenges including phenotypic heterogeneity with significant asymmetry, coexisting ocular and systemic disease, limited understanding of human eye development and the associated genetic repertoire, and lack of access to next generation sequencing as regarded not to impact on patient outcomes/management with cost implications. Herein, we report our real world experience from a pediatric ocular genetics service over a 12 month period with 72 consecutive patients from 62 families, and that from a cohort of 322 patients undergoing whole genome sequencing (WGS) through the Genomics England 100,000 Genomes Project; encompassing microphthalmia, anophthalmia, ocular coloboma (MAC), anterior segment dysgenesis anomalies (ASDA), primary congenital glaucoma, congenital cataract, infantile nystagmus, and albinism. Overall molecular diagnostic rates reached 24.9% for those recruited to the 100,000 Genomes Project (73/293 families were solved), but up to 33.9% in the clinic setting (20/59 families). WGS was able to improve genetic diagnosis for MAC patients (15.7%), but not for ASDA (15.0%) and congenital cataracts (44.7%). Increased sample sizes and accurate human phenotype ontology (HPO) terms are required to improve diagnostic accuracy. The significant mixed complex ocular phenotypes distort these rates and lead to missed variants if the correct gene panel is not applied. Increased molecular diagnoses will help to explain the genotype–phenotype relationships of these developmental eye disorders. In turn, this will lead to improved integrated care pathways, understanding of disease, and future therapeutic development.

In order to summarize recent research on the prevention of allergies—particularly asthma—and stimulate new activities for future initiatives, a virtual workshop sponsored by the EAACI Clemens von Pirquet foundation and EUFOREA was held in October 2021. The determinants of the “allergic march” as well as the key messages from intervention studies were reviewed by an international faculty of experts. Several unmet needs were identified, and a number of priorities for future studies were proposed.

Here, the feasibility of using nonimaging pulse-echo ultrasound as a method of noninvasively detecting a bolus in the proximal esophagus was demonstrated. To accomplish this, patient swallows were recorded on a clinical ultrasound device with research interface that allowed for collection of the pulse-echo data. These ultrasound data of the proximal esophagus were processed with a series of signal processing techniques in both the temporal and spectral domains, which revealed characteristic signatures that were unique for both liquid and food boluses compared to the normal collapsed esophageal state. Since substantial amounts of laryngopharyngeal reflux are gaseous in nature, future work will revolve around expanding the data set to include boluses of gaseous refluxate, a standardized methodology for capturing bolus events; developing automated detection tools for identifying laryngopharyngeal reflux for an extended duration; and assessing technology limitations due to user error.

Mitochondria are essential organelles which perform complex and varied functions within eukaryotic cells. Maintenance of mitochondrial health and functionality is thus a key cellular priority and relies on the organelle's extensive proteome. The mitochondrial proteome is largely encoded by nuclear genes, and mitochondrial proteins must be sorted to the correct mitochondrial sub-compartment post-translationally. This essential process is carried out by multimeric and dynamic translocation and sorting machineries, which can be found in all four mitochondrial compartments. Interestingly, advances in the diagnosis of genetic disease have revealed that mutations in various components of the human import machinery can cause mitochondrial disease, a heterogenous and often severe collection of disorders associated with energy generation defects and a multisystem presentation often affecting the cardiovascular and nervous systems. Here, we review our current understanding of mitochondrial protein import systems in human cells and the molecular basis of mitochondrial diseases caused by defects in these pathways.

Human Tim8a and Tim8b are members of an intermembrane space chaperone network, known as the small TIM family. Mutations in TIMM8A cause a neurodegenerative disease, Mohr-Tranebjærg syndrome (MTS), which is characterised by sensorineural hearing loss, dystonia and blindness. Nothing is known about the function of hTim8a in neuronal cells or how mutation of this protein leads to a neurodegenerative disease. We show that hTim8a is required for the assembly of Complex IV in neurons, which is mediated through a transient interaction with Complex IV assembly factors, in particular the copper chaperone COX17. Complex IV assembly defects resulting from loss of hTim8a leads to oxidative stress and changes to key apoptotic regulators, including cytochrome c, which primes cells for death. Alleviation of oxidative stress with Vitamin E treatment rescues cells from apoptotic vulnerability. We hypothesise that enhanced sensitivity of neuronal cells to apoptosis is the underlying mechanism of MTS.

Summary: Mitochondrial complex I harbors 7 mitochondrial and 38 nuclear-encoded subunits. Its biogenesis requires the assembly and integration of distinct intermediate modules, mediated by numerous assembly factors. The mitochondrial complex I intermediate assembly (MCIA) complex, containing assembly factors NDUFAF1, ECSIT, ACAD9, and TMEM126B, is required for building the intermediate ND2-module. The role of the MCIA complex and the involvement of other proteins in the biogenesis of this module is unclear. Cell knockout studies reveal that while each MCIA component is critical for complex I assembly, a hierarchy of stability exists centered on ACAD9. We also identify TMEM186 and COA1 as bona fide components of the MCIA complex with loss of either resulting in MCIA complex defects and reduced complex I assembly. TMEM186 enriches with newly translated ND3, and COA1 enriches with ND2. Our findings provide new functional insights into the essential nature of the MCIA complex in complex I assembly. : Formosa et al. investigate the function of the MCIA complex in complex I assembly. They demonstrate the requirement of individual components for the formation of complex I intermediates and assembly of the final enzyme. Finally, they characterize the involvement of TMEM186 and COA1 in this process. Keywords: assembly factors, complex I, MCIA complex, mitochondria, NADH-ubiquinone dehydrogenase, oxidative phosphorylation

Spatial Augmented Reality (SAR) systems can be suitably combined with other existing Extended Reality (xR) technologies to support collaboration. In existing strategies, users unencumbered by a viewing technology, such as a tablet interface or a head-mounted display, must rely on the transmission of their collaborators' positioning through interpreting a first-person camera view. This design creates a seam between a user's experience of the augmented physical environment in SAR, and their collaborators' experience inside the virtual environment. To assist in development and evaluation of spatial cues to support spatial awareness in SAR environments, an egocentric spatial-communication taxonomy is presented given two determining dimensions, a cue's attachment (physical/virtual) and animation (local/world). We developed four egocentric cues which characterize the four independent dimensions of the matrix: arrow, path, glow, and radial, and a single exocentric world in miniature visualization. Our study shows that virtual attachment cues are preferred, providing the highest accuracy, highest performance when collaborators are occluded, and produce the least mental effort when used with a single virtual collaborator. For multiple collaborators however, the virtual attached, world animated radial cue produces significant increases in mental load and reductions in preference, demonstrating the impact of visual augmentation clutter. The single exocentric visualization produced higher levels of head movement, and poorer accuracy, however the novelty of the visualization produced positive qualitative results. Refereed/Peer-reviewed

Mitochondria are iconic structures in biochemistry and cell biology, traditionally referred to as the powerhouse of the cell due to a central role in energy production. However, modern-day mitochondria are recognized as key players in eukaryotic cell biology and are known to regulate crucial cellular processes, including calcium signalling, cell metabolism and cell death, to name a few. In this review, we will discuss foundational knowledge in mitochondrial biology and provide snapshots of recent advances that showcase how mitochondrial function regulates other cellular responses.

There is a dearth of information regarding sexual behavior in patients with bipolar illness.A questionnaire regarding sexual and reproductive behavior was administered to all willing attendees of an academic bipolar clinic. Information regarding onset, maintenance, and nature of sexual behaviors, as well as marriage and children, was collected.Patients with bipolar disorder have less children on average (1.6) than the U.S. general population (1.87). Patients were 3 times more likely to have planned children before diagnosis than after; however, the average number of unplanned children remained the same before and after diagnosis. In the U.S., 55.7% of those age 18 and older are married, compared with 32.8% among bipolar patients. The majority of patients, 52.9%, believed that stigma towards bipolar illness had affected relationships, and 32.4% believed that stigma affected finding sexual partners, but measurement of subjective stigma did not correlate with reproductive success.Individuals with bipolar illness have a wide range of sexual experiences. However, reproductive success of people diagnosed with bipolar illness is limited.

When the Deepwater Horizon oil rig blew out in 2010, the immediate threats to productive deep water and estuarial fisheries and the region’s fishing and energy economies were obvious. Less immediately obvious, but equally unsettling, were risks to human health posed by potential damage to the regional food web. This paper describes grassroots and regional efforts by the Gulf Coast Health Alliance: health risks related to the Macondo Spill Fishermen’s Citizen Science Network project. Using a community-based participatory research approach and a citizen science structure, the multiyear project measured exposure to petrogenic polycyclic aromatic hydrocarbons, researched the toxicity of these polycyclic aromatic hydrocarbon compounds, and communicated project findings and seafood consumption guidelines throughout the region (coastal Louisiana, Mississippi, and Alabama). Description/analysis focuses primarily on the process of building a network of working fishermen and developing group environmental health literacy competencies.

Uveitis is a frequently occurring extra-articular manifestation of spondyloarthropathies (SpAs), ankylosing spondylitis (AS), reactive arthritis (ReA), psoriatic arthritis (PsA) and inflammatory bowel disease (IBD), occurring in both adults and children with SpA. Uveitis occurs with varying frequency according to the SpA subtype (33% in AS, 6-9% in PsA, 25% in ReA, 13% in undifferentiated SpA and 2-5% in IBD), the presence of HLA-B27 and with increasing duration of disease. The majority of cases of uveitis in SpA are attributed to acute anterior uveitis but a minority of uveitis cases occur in the posterior segment of the eye. The latter are more frequently complicated by cystoid macular oedema (CMO) and sight loss. The nature of the tissue specificity exhibited by the SpAs is poorly understood. Three current investigational approaches are discussed: high-throughput genomics to identify and confirm uveitis-specific susceptibility alleles; investigation of the role of the intestinal microbiome and its potential role in innate immune signalling in uveitis; and study of a novel IL23R-bearing cell population in several entheseal sites including the eye. The treatment for uveitis in SpAs is predominantly with topical corticosteroids for acute episodes. Among the systemic drugs used for the treatment of SpAs, infliximab, adalimumab and certolizumab are effective in reducing the frequency of uveitis but etanercept is not. Other targets in spondyloarthropathy include cytokines within the IL23/IL17 axis, of which the IL17A inhibitor secukinumab has not been shown to be effective in uveitis. Future therapeutic approaches may include small molecules such as selective and non-selective janus kinase and tyrosine kinase inhibitors.

This study appraises the effectiveness and cost-effectiveness of consumption of plant sterol-enriched margarine-type spreads for the prevention of cardiovascular disease (CVD) in people with hypercholesterolemia in England, compared to a normal diet. A nested Markov model was employed using the perspective of the British National Health Service (NHS). Effectiveness outcomes were the 10-year CVD risk of individuals with mild (4–6 mmol/l) and high (above 6 mmol/l) cholesterol by gender and age groups (45–54, 55–64, 65–74, 75–85 years); CVD events avoided and QALY gains over 20 years. This study found that daily consumption of enriched spread reduces CVD risks more for men and older age groups. Assuming 50% compliance, 69 CVD events per 10,000 men and 40 CVD events per 10,000 women would be saved over 20 years. If the NHS pays the excess cost of enriched spreads, for the high-cholesterol group, the probability of enriched spreads being cost-effective is 100% for men aged over 64 years and women over 74, at £20,000/QALY threshold. Probabilities of cost-effectiveness are lower at younger ages, with mildly elevated cholesterol and over a 10-year time horizon. If consumers bear the full cost of enriched spreads, NHS savings arise from reduced CVD events.

The Deepwater Horizon (DWH) explosion in 2010 is the largest oil spill (Macondo) in U.S. history. We focused on gaining an understanding of the physical health and mental health effects attributable to the Macondo oil spill. This is a report of a cross-sectional cohort study (wave 1) to establish ‘baseline’ findings and meant to provide descriptive information to be used for a multi-wave, longitudinal study. Gulf Coast Health Alliance: health Risks related to the Macondo Spill (GC-HARMS) uses a Community-Based Participatory Research approach, thus including multi-disciplinary, multi-institutional academic partners and representatives of three communities impacted by the spill. Three research sites were selected for human sampling along the Gulf of Mexico coast including two from Mississippi and one from Louisiana, with Galveston, Texas, serving as a comparison site, given that it was not directly impacted by the spill. One hundred participants were selected from each community, representing adults, seniors and children, with approximately equal numbers of males and females in each group. Participants completed initial assessments including completion of a ‘baseline’ survey and, rigorous physical assessments. Results from wave 1 data collection reported herein reveal changes in self-reported physical health and mental health status following the oil spill, disparities in access to healthcare, and associations between mental health and emotional conditions related to displacement/unemployment. Few environmental health studies have been conducted in communities impacted by significant oil spills. Results imply potential prolonged effects on mental health and community vulnerability.

Pediatric patients who are receiving parenteral nutrition (PN) unsupplemented with trace minerals can become deficient. Due to shortages in trace mineral products and the 2004 American Society for Parenteral and Enteral Nutrition report stating that individualized trace element supplementation may be warranted, a review was conducted concerning the trace minerals selenium (Se), manganese (Mn), and iodine (I).A retrospective review of pediatric patients receiving PN that contained Se and Mn was conducted to determine if a difference existed between them and patients receiving PN without Se and Mn. Statistical analysis was done to assess a difference between trace mineral levels and the time to deficiency between supplemented and unsupplemented patients. Unsupplemented I patients had urine I levels assessed to determine deficiencies in patients receiving PN.Plasma Se levels were measured at a mean of 20 days for supplemented patients (n = 131) and 19 days for nonsupplemented patients (n = 57) with no difference between groups ( P = .2973). Plasma Mn levels were measured at a mean of 28 days, showing no statistical difference ( P = .721). Of the 177 nonsupplemented I patients, 74% demonstrated I deficiencies without supplementation.Time to the development of a Se, Mn, or I deficiency is important to guide supplementation of exclusive PN in children when trace mineral products are short in supply. Our retrospective experience supports assessment of the trace minerals Se at 21 days and Mn at 30 days. It also suggests that some pediatric patients receiving PN are deficient in I.

A consumer study was conducted to evaluate preferences in Vidalia onions, and define consumer acceptability thresholds for commonly analyzed flavor compounds associated with pungency. Two varieties of Vidalia onions (Plethora and Sapelo Sweet) were grown at 3 fertilizer application rates (37.5 and 0; 134.5 and 59.4; and 190 and 118.8 kg/ha of nitrogen and sulfur, respectively), creating 6 treatments with various flavor attributes to use in the study. Bulb soluble solids, sugars, pyruvic acid, lachrymatory factor (LF; propanethial S-oxide), and methyl thiosulfinate (MT) content were determined and compared to sensory responses for overall liking, intensity of the sharp/pungent/burning sensation (SPB), and intent to buy provided by 142 consumers. Onion pyruvate, LF, MT, and sugar content increased as fertilization rate increased, regardless of onion variety. Consumer responses showed participants preferred onions with low SPB, which correlated positively to lower pyruvate, LF and MT concentrations, but showed no relationship to total sugars in the onion bulb. Regression analyses revealed that the majority of consumers (≥55%) found the flavor of Vidalia onions acceptable when the concentrations of LF, pyruvic acid, and MT within the bulbs were below 2.21, 4.83, and 0.43 nmol/mL, respectively. These values will support future studies aimed at identifying the optimal cultivation practices for production of sweet Vidalia onions, and can serve as an industry benchmark for quality control, thus ensuring the flavor of Vidalia onions will be acceptable to the majority of consumers.This study identified the relationship between consumer preferences and commonly analyzed flavor compounds in Vidalia onions, and established thresholds for these compounds at concentrations which the majority of consumers will find desirable. These relationships and thresholds will support future research investigating how cultural practices impact onion quality, and can be used to assist growers in variety selection decisions. In addition, this information will provide a benchmark to Vidalia onion producers for quality control of the sweet onions produced, ensuring that the onions are consistently of a desired quality, thereby increasing consumer's reliability in the Vidalia onion brand.

Copper is a trace mineral essential for numerous physiological processes. The purpose of this article is to provide data on copper levels in pediatric patients receiving parenteral nutrition (PN) that are useful to guide supplementation in PN formulation.This is a retrospective review of hospitalized pediatric patients receiving PN supplemented and not supplemented with copper. In total, 751 supplemented pediatric patients and 90 pediatric patients not supplemented had serum copper levels measured. We assessed patient demographics, days on PN before copper level was drawn, serum copper levels, conjugated bilirubin levels, and C-reactive protein (CRP).The mean serum copper level was 80 mcg/dL at 20 days for supplemented patients and 64 mcg/dL at 14 days for the 90 nonsupplemented patients (P = .0002). In the supplemented patients, 50% of the levels were low and 45% were within the normal range. The remaining 5% of patients had high levels. In nonsupplemented patients, 71% were low and 29% within the normal range. There was no correlation between copper levels and conjugated bilirubin2 mg/dL and2 mg/dL (P = .3421). Copper levels correlated with CRP for CRP4 mg/dL (P = .03).Pediatric patients receiving PN should be supplemented with copper to prevent deficiency. Serum copper levels should be assessed at 14 days. Assessment of copper status should not be determined by conjugated bilirubin levels. Serum copper levels may be elevated in patients with acute inflammation and may be falsely elevated when CRP is4 mg/dL.

BACKGROUND: Recurrent preschool wheezing is a heterogeneous disorder with significant morbidity, yet little is known about phenotypic determinants and their impact on clinical outcomes. OBJECTIVE: Latent class analysis (LCA) was used to identify latent classes of recurrent preschool wheeze and their association with future exacerbations and inhaled corticosteroid (ICS) treatment response. METHODS: Data from five clinical trials of 1,708 children age 12–71 months with recurrent wheezing were merged. LCA was performed on 10 demographic, exposure and sensitization variables to determine the optimal number of latent classes. The primary outcome was the annualized rate of wheezing exacerbations requiring systemic corticosteroids during the study intervention period; the secondary outcome was the time to first exacerbation. Exploratory analyses examined the effect of daily ICS treatment on exacerbation outcomes. RESULTS: Four latent classes of recurrent wheezing were identified; these were not distinguished by current symptoms or historical exacerbations but differed with regard to allergen sensitization and/or exposures. Annualized exacerbation rates (mean ± SEM/year) were 0.65 ± 0.06 for class 1 (“minimal sensitization”), 0.93 ± 0.10 for class 2 (“sensitization with indoor pet exposure”), 0.60 ± 0.07 for class 3 (“sensitization with tobacco smoke exposure”), and 0.81 ± 0.10 for class 4 (“multiple sensitization and eczema”) (p < 0.001). In a research setting of high adherence, daily ICS treatment improved exacerbation rates in classes 2 and 4 but not the other groups. CONCLUSION: Sensitization and exposure assessments are useful in the prediction of future exacerbation and may identify children most likely to respond favorably to daily ICS treatment.

Purpose We performed a pilot trial to compare reduced dose versus standard soybean lipid emulsion in neonates at risk for parenteral nutrition-associated liver disease. Methods A prospective randomized controlled trial was performed (2009–2011) enrolling surgical patients ≥26weeks' gestation anticipated to require >50% of daily caloric intake from parenteral nutrition (PN) for at least 4weeks. Randomization occurred into either reduced (1.0g/kg/day) or standard (3 g/kg/day) groups. Co-primary outcomes for interpretation of the results were conjugated bilirubin and total bile acids. Additional outcomes included ALT, AST, GGT, alkaline phosphatase, growth, and essential fatty acid levels. Outcomes were compared between treatment groups using Wilcoxon rank sums tests. Results Twenty-eight patients (47% enrollment rate) were included in the study with an average treatment duration of 5.4weeks. Groups had similar PN calories and protein intake throughout the study. Total increase from baseline was smaller in the reduced vs. standard group for conjugated bilirubin ( p =0.04) and total bile acids ( p =0.02). Weight z-score increased more in the standard group, and no patient experienced essential fatty acid deficiency. Conclusion Markers of cholestasis rose at a slower rate using reduced lipid doses. This pilot study demonstrates feasibility and need for a larger study evaluating the effects of reduced lipids in patients at risk for developing parenteral nutrition-associated liver disease.

Objectives: Evidence of how health-related quality of life (HRQOL) changes following laparoscopic and open colorectal surgery in the first 6 weeks of postoperative recovery is needed to inform cost-effectiveness evaluations. Methods: Pragmatic prospective cohort study design. Consecutive patients requiring elective colorectal surgery were allocated to either laparoscopic or open surgery by administrative staff in a district general hospital in England, 2006-2007. Patients completed two validated, generic measures of HRQOL at baseline (preoperatively) and on multiple occasions in the first 6 weeks postsurgery using diaries (EuroQol five-dimensional [EQ-5D] questionnaire: 16 times; short-form 36 health survey [SF-36]: 4 times; HRQOL was compared between groups at each time point, and overall using repeated-measures analysis. Results: Of 201 consecutive patients recruited, 32 (15.1%) were unable to complete diaries. Of the remaining 169 patients, 120 (71%) returned completed diaries at 28 days and 105 (62.1%) at 42 days. There was no difference in preoperative HRQOL scores between surgical groups, but the postoperative EQ-5D questionnaire and SF-36 scores were significantly higher in the laparoscopic group (EQ-5D questionnaire P = 0.005, SF-36 P = 0.007). Subgroup analysis showed that patients with a stoma have worse HRQOL than those without. HRQOL did not differ between the laparoscopic and open stoma patients. Conclusions: This study presents unique prospective data demonstrating that laparoscopic surgery confers HRQOL benefits for patients in the early recovery period following colorectal surgery, compared with open surgery. Consideration of these data in the context of a cost-effectiveness analysis will be reported separately. © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR).

Acinar cells represent the primary target in necroinflammatory diseases of the pancreas, including pancreatitis. The signaling pathways guiding acinar cell repair and regeneration following injury remain poorly understood. The purpose of this study was to determine the importance of Hepatocyte Growth Factor Receptor/MET signaling as an intrinsic repair mechanism for acinar cells following acute damage and chronic alcohol-associated injury. Here, we generated mice with targeted deletion of MET in adult acinar cells (MET-/-). Acute and repetitive pancreatic injury was induced in MET-/- and control mice with cerulein, and chronic injury by feeding mice Lieber-DeCarli diets containing alcohol with or without enhancement of repetitive pancreatic injury. We examined the exocrine pancreas of these mice histologically for acinar death, edema, inflammation and collagen deposition and changes in the transcriptional program. We show that MET expression is relatively low in normal adult pancreas. However, MET levels were elevated in ductal and acinar cells in human pancreatitis specimens, consistent with a role for MET in an adaptive repair mechanism. We report that genetic deletion of MET in adult murine acinar cells was linked to increased acinar cell death, chronic inflammation and delayed recovery (regeneration) of pancreatic exocrine tissue. Notably, increased pancreatic collagen deposition was detected in MET knockout mice following repetitive injury as well alcohol-associated injury. Finally, we identified specific alterations of the pancreatic transcriptome associated with MET signaling during injury, involved in tissue repair, inflammation and endoplasmic reticulum stress. Together, these data demonstrate the importance of MET signaling for acinar repair and regeneration, a novel finding that could attenuate the symptomology of pancreatic injury.

Eligibility for thrombolysis as an acute stroke treatment is determined through the use of unenhanced noncontrast computed tomography (CT), time since stroke onset, and patient history. Assessing penumbral patterns, which can be examined only through the use of diagnostic technologies such as magnetic resonance imaging (MRI) and perfusion CT (CTP), may be able to better select patients for thrombolysis. However, trade-offs in terms of administration time and cost may affect the value of using these diagnostic studies.We examined the trade-offs among patient selection via usual care with CT, usual care plus MRI using diffusion-weighted and perfusion imaging, and usual care plus CTP for their effect on costs and outcomes when diagnosing stroke and selecting candidates for thrombolysis in the United Kingdom.A decision-analytic model was developed. Efficacy and utilities were obtained from published studies. Costs were obtained from standard UK costing sources and were supplemented with data from the published literature. Outcomes included a favorable outcome (modified Rankin Scale score2), costs, life-years, quality-adjusted life-years, and incremental cost-effectiveness ratios.Compared with usual care selection, adding CTP or MRI to better select patients for thrombolysis reduced the number of patients receiving thrombolysis by 9 and 14.6 per 1000 patients treated, respectively, while improving favorable outcome (19.2 and 17.6 per 1000 patients treated, respectively). In both scenarios, costs were decreased slightly. Both CTP and MRI selection were cost saving (more efficacious and less costly) compared with unenhanced CT selection; CTP selection was found to dominate MRI selection.Adding diagnostic tests such as CTP and MRI to select UK patients for thrombolysis may be a good value for the money and may improve patient outcomes. If a preferred diagnostic test had to be chosen based on economic value, CTP might be the best compromise between unenhanced CT selection and MRI selection.

OBJECTIVE: To evaluate for adverse outcomes associated with gastroesophageal reflux disease (GERD) following an apparent life-threatening event (ALTE) and potential risk factors of these outcomes. STUDY DESIGN: Retrospective cohort study of well-appearing infants (

Transient ischemic attack (TIA) is a serious condition which should be considered on the same spectrum as other conditions involving brain ischemia. Efficient management of these patients is therefore critical. The aim of this research was to gain insights into 'real-world' global trends of the current management approaches for patients with suspected and diagnosed TIA, and highlight the unmet need and areas of improvement to ensure effective management of this patient group.Tele-interviews were conducted with 120 physicians and five operational managers across France, Germany, Italy, Spain, UK, and the US including stakeholders from primary care group practice, those with hospital responsibilities (ER physician and Neurologists), or from home health agencies. Information from the interviewees regarding the management of patients with TIA (including entrance into the clinical pathway, diagnosis, and treatment) were obtained and analyzed qualitatively.The majority of patients with suspected TIA were reported to enter the clinical pathway via the GP or ER, irrespective of country. Once initially seen, the neurologist then plays a central role in the diagnosis, treatment and follow-up of the patients. Although a number of tests are routinely employed, interviewees reported that streamlining and simplification of diagnosis, faster initiation of treatment, improved efficacy and fewer side-effects with treatment were needed for patients with suspected TIA. The study is designed to provide a directional indication of the current situation rather than strong, quantitative conclusions, given limitations of the small sample size and subjective nature of the data.The importance of correct management of patients with TIA is becoming increasingly recognized by physicians. Improved education for patients regarding symptom recognition and severity is required along with a standardized diagnostic process. These would enable correct and fast diagnosis and initiation of treatment thereby reducing the risk of further events.

Background: Clinical variables may identify a subset of patients with pediatric-onset ulcerative colitis (UC) (≤18 years at diagnosis) at risk for adverse outcomes. We postulated that routinely measured clinical variables measured at diagnosis would predict colectomy in patients with pediatric-onset UC. Methods: We conducted a chart review of patients with pediatric-onset UC at a single center over a 10-year period. We compared patients with and without colectomy across several variables, used proportional hazards regression to adjust for potential confounders, and assessed the ability of a UC risk score to predict colectomy. Results: Among 470 patients with inflammatory bowel disease ICD9-coded encounters, 155 patients had UC and 135 were eligible for analysis. The 1- and 3-year colectomy rates were 16.7% (95% confidence interval [CI]: 11.0%–24.8%) and 35.6% (26.7%–45.4%). White blood cell (WBC) count and hematocrit measured at diagnosis were associated with colectomy at 3 years, even after correcting for potential confounding variables. A UC Risk Score derived from the WBC count and hematocrit was strongly associated with colectomy risk, with a high negative predictive value (NPV) for colectomy at 1 and 3 years (NPV = 0.95 and 0.89, respectively), but low positive predictive value (PPV = 0.22 and 0.38, respectively). Conclusions: A risk score calculated from WBC and hematocrit measured at diagnosis was associated with, but incompletely predictive of, colectomy in pediatric-onset UC. These data suggest 1) routinely measured clinical variables may have a prognostic role in risk stratification, and 2) multicenter prospective studies are needed to optimize risk stratification in pediatric UC. Our findings have impact on the design of such studies. (Inflamm Bowel Dis 2011;)

To determine if participation in a learning collaborative (LC) would improve care processes for prevention, early recognition, and treatment of childhood obesity by primary care physicians (PCP), the authors conducted pre-post evaluations of the use of obesity related care processes by 18 primary care practices following participation in a 9-month LC based on the Model for Improvement. Prior to the LC, chart audits revealed that 55% of patients had a BMI recorded; this rose to 97% of patients at its conclusion. Following the LC, 11 practices had implemented systematic prevention advice to parents of infants compared with 3 prior to the LC. All practices developed plans for evaluation and management of children with an elevated BMI. Participation in an LC increased the number of primary care practices that provided anticipatory guidance regarding obesity prevention and that identified and treated overweight or obese children.

Parenteral nutrition-associated liver disease (PNALD) is a potentially fatal complication for children with intestinal failure. Fish oil-based lipid emulsions have shown promise for the treatment of PNALD but are not readily available. Six cases are presented in which cholestasis resolved after soybean lipid emulsion (SLE) was removed from parenteral nutrition (PN) and enteral fish oil was given.A retrospective review at a tertiary children's hospital (July 2003 to August 2008) identified 6 infants with intestinal failure requiring PN for6 months who developed severe hepatic dysfunction that was managed by eliminating SLE and providing enteral fish oil.Twenty-three infants with short bowel syndrome requiring prolonged PN developed cholestasis. SLE was removed in 6 of these patients, and 4 of the 6 received enteral fish oil. Standard PN included 2-3 g/kg/d SLE with total PN calories ranging from 57 to 81 kcal/kg/d at the time of SLE removal. Hyperbilirubinemia resolved after elimination of SLE within 1.8-5.4 months. Total PN calories required to maintain growth generally did not change.Temporary elimination of SLE and supplementation with enteral fish oil improved cholestasis in PN-dependent infants. Further trials are needed to evaluate this management strategy.

To estimate the clinical outcomes and costs associated with reconfiguring the management of TIA in the UK to offer patients rapid access to outpatient clinics for specialist assessment and treatment.An economic deterministic model was run comparing two pathways--one arm representing current clinical care based on national guidelines and clinical practice and patient referral to a weekly outpatient clinic, and a revised care pathway replicating phase 2 of the EXPRESS study with patient referral to a daily outpatient clinic. The outcomes of the model were measured in terms of recurrent strokes avoided and net budget impact to secondary care.Reconfiguring TIA care pathways in the UK could result in the avoidance of 8,164 recurrent stroke events. The model predicts savings of £25,573,279 for the UK healthcare system over 12 months. Annual net savings are predicted in England (£24,916,011), Scotland (£80,554) and Northern Ireland (£1,041,817). In Wales, increased costs of £450,435 are estimated.Using the data published from the EXPRESS study, it is not possible to model a stepwise approach to implementing the revised TIA care pathway. It is therefore assumed that it would be possible to implement the revised TIA care pathway as detailed in the EXPRESS study across the UK and achieve the reduction in recurrent stroke risk that was reported.The model suggests that the reconfiguration of TIA care pathways in the UK to offer rapid access to treatment and assessment could prevent TIA-related future stroke events and potentially result in cost savings to the healthcare system.

Many institutions reduce or eliminate copper (Cu) and manganese (Mn) in parenteral nutrition (PN) solutions when cholestasis develops. Little data exist to support this practice. Fifty-four subjects with known serum Cu, whole-blood Mn, and serum-conjugated bilirubin levels were evaluated in this prospective, observational study. Subjects ranged in weight from 760 g to 65.2 kg. Subjects weighing25 kg received a daily parenteral dose of 20 microg/kg Cu and 5 microg/kg Mn. Subjects weighingor =25 kg received a dose of 500 microg/d Cu and 150 microg/d Mn. Cholestasis was defined as a conjugated bilirubin levelor =2 mg/dL. Of the 54 subjects, 20 had cholestasis. Fifteen patients had elevated Cu levels, and 21 had high Mn levels. Seven of the subjects had both high Cu and high Mn levels. The regression model comparing cholestasis as a predictor of high, low, or normal Cu level was not significant (P = .9588). Cholestasis was not a significant predictor of high, low, or normal Mn levels (P = .6533). No correlation between Cu and Mn levels was found. The authors found no significant relationship between conjugated serum bilirubin levelsor =2.0 mg/dL, serum Cu, and whole-blood Mn levels. They found insufficient evidence to support the practice of dosing Mn from a Cu level or vice versa. They recommend obtaining Cu and Mn levels on all pediatric patients who develop cholestasis prior to adjusting parenteral doses and at regular intervals for all long-term PN patients.

IgA antibodies against tissue transglutaminase (TTGA) and endomysium (EMA) are sensitive and specific markers for celiac disease (CD). Data correlating TTGA and EMA levels with degree of villous atrophy are limited. We compared duodenal histopathology in pediatric CD patients with TTGA and EMA serologies, symptoms, height, and weight.We identified 117 pediatric patients retrospectively who had serologic testing for IgA TTGA and IgA EMA and duodenal biopsies graded by modified Marsh criteria as 0-3c. Data were analyzed with Spearman rank correlation and multinomial logistic regression.IgA TTGA (r = .704, P.001) and IgA EMA (r = 0.740, P.001) correlated with intestinal villous atrophy in pediatric CD patients by Spearman rank correlation. Similar correlations were found in a subset of 23 patients younger than 3 years of age. Multinomial logistic regression revealed increased probability of Marsh 3a or greater changes with increasing TTGA or EMA levels. Strongly positive antibody levels (TTGA100 units or EMA titer1:1280) were highly specific (98%) for Marsh 3a or greater lesions. Among symptoms, abdominal distention and diarrhea were associated with abnormal histology.IgA TTGA and EMA levels correlate with duodenal villous atrophy in pediatric CD patients. IgA TTGA100 or EMA1:1280 were nearly always associated with CD histopathology. With further validation of this observation, strongly positive titers might be considered sufficient for diagnosis of pediatric patients at risk for CD. Symptoms, height, and weight are not reliable predictors of CD.

Objective Follicular tracheitis (also known as tracheal cobblestoning) is an entity that is poorly described and of unclear significance. The objective of this study was to better define follicular tracheitis and determine the association between the clinical finding of follicular tracheitis on bronchoscopy and objective evidence of gastroesophageal reflux disease. Methods Retrospective chart review of children with recurrent croup having undergone a rigid bronchoscopy and an investigation for gastroesophageal reflux between 2001 and 2013. Results 117 children with recurrent croup children age 6–144 months were included in the study. Follicular tracheitis was noted on 41% of all bronchoscopies. Fifty-nine percent of all children who underwent bronchoscopy were diagnosed with gastroesophageal reflux on at least one investigation. Forty-nine of 117 children underwent a pH probe study, and 51% were found to have evidence of reflux on this study. Nine children were diagnosed with eosinophilic esophagitis. Three patients underwent a biopsy of the follicular tracheitis lesions, which revealed chronic inflammation. There was no evidence of an association between findings of follicular tracheitis and a positive test for gastroesophageal reflux ( p = 0.52) or a positive pH probe study ( p = 0.64). There was no association between follicular tracheitis and subglottic stenosis ( p = 0.33) or an history of asthma and/or atopy ( p = 0.19). Conclusion In children with recurrent croup, follicular tracheitis remains an unspecific finding associated with an inflammatory disorder of unknown etiology.

Objectives Alkaptonuria is a rare autosomal recessive condition resulting from inability to breakdown homogentisic acid (HGA); an intermediate in tyrosine degradation. The condition has a triad of clinical features, the most damaging of which is ochronotic osteoarthropathy. HGA is elevated from birth but pigmentation takes many years. We hypothesise that interleukins play a role in initiation and progression of ochronotic osteoarthropathy. Methods C20/A4 cells were cultured and maintained in 9cm petri dishes containing either HGA at 0.33mM, a single interleukin (IL-1β, IL-6 or IL-10) at 1ng/ml or a combination of HGA and a single interleukin. Statistical analysis of pigment deposits and cell viability was performed using analysis of variance with Newman-Keuls post-test. Results All cultures containing HGA showed a significant increase in pigment deposition compared to control and IL cultures alone. The cultures containing HGA and IL-6 showed a significant increase in pigment deposits compared to HGA alone. The cell viability counts across all cultures on day 10 demonstrated a significant decrease in cultures containing HGA compared to those which did not. There was no significant difference between cultures containing just HGA or those combined with an interleukin. Conclusions This work demonstrates a role for cytokines present in the joint(s) in the pigmentation process, particularly IL-6 and that the presence of HGA in joint tissues appears more detrimental to chondrocytes than the presence of any of the interleukins found in response to joint injury, trauma and OA. This further supports the evidence that the arthropathy in alkaptonuria is much more severe and rapidly progressing.

To evaluate fetal epicardial fat thickness (EFT) in diabetic and control pregnancies.A retrospective cross-sectional study was performed in which fetal EFT was measured in the second trimester in 28 diabetics and 28 non-diabetic patients. Maternal BMI, estimated fetal weight, birth weight, fetal abdominal circumference, and subcutaneous fat thickness were also collected. Statistical analysis was carried out by means of chi-square, Wilcoxon rank-sum test, Student's T test, and linear regression as appropriate.EFT was significantly higher in diabetic (1.43 mm) vs. control fetuses (1.16 mm), P = 0.02. This relationship remained significant when controlling for covariates.EFT was higher in fetuses of diabetic mothers vs. fetuses from controls. If confirmed in prospective studies, this may represent a novel marker for altered fetal metabolism due to maternal diabetes.

Esophageal foreign body is a frequent pediatric presentation, and eosinophilic esophagitis (EoE) is an important underlying disease. To determine characteristics common in the presentation of esophageal foreign body indicative of underlying EoE and reach a recommendation for the appropriate scenario in which to obtain esophageal mucosal biopsy, 312 pediatric esophageal foreign bodies requiring operative removal were reviewed. Patients older than 18 years or with a known history of esophageal surgery or pathology were excluded. Eligibility criteria were met in 271 cases. Twenty-seven patients were biopsied, and 18 were diagnosed with EoE. The following factors were identified in the EoE population: food impaction (89%), older age (average 12.2 years), male sex (78%), atopic disease (61%), previous esophageal foreign body or frequent dysphagia (83%), and endoscopic abnormalities (100%). These factors are all associated with an underlying diagnosis of EoE, and patients meeting these criteria should be strongly considered for intraoperative esophageal mucosal biopsy.

Gastrointestinal polyps and certain extraintestinal lesions in children may herald a hereditary polyposis syndrome, with an increased risk of neoplasia and other health problems for both children and their relatives. The availability of molecular/genetic screening tests has increased early diagnosis of younger members of known polyposis families. This article reviews the gross and microscopic features of polyposis syndromes of childhood and summarizes the molecular/genetic advances in this field. Clinical management is also briefly discussed.

The present paper proposes an analytical method for fast near-infrared (NIR) determination of dipyrone in injectable formulations with a nominal content of 50.0% m v−1 without violation of the ampoule. For this purpose, two multivariate calibration methods are evaluated, namely Partial-Least-Squares (PLS) and Multiple Linear Regression (MLR) with variable selection by the Successive Projections Algorithm (SPA). The resulting models comprised four latent variables (PLS) and five spectral variables (MLR-SPA). Appropriate predictions were obtained in both cases, with RMSEP values of 0.39 (PLS) and 0.35% m v−1 (MLR-SPA) and correlation coefficients of 0.9970 (PLS) and 0.9975 (MLR-SPA) for a calibration range of 40–60% m v−1. No systematic error was observed and no significant differences were found between the predicted and reference values, according to a paired t-test at 95% confidence level.

PURPOSE: To investigate patients’ willingness to pay for advanced technology intraocular lenses and surgeons’ willingness to recommend them. METHODS: In this study, 370 cataract surgeons and 700 patients undergoing cataract surgery from seven countries underwent online interviews in which they were shown unbranded profiles of three advanced technology intraocular lenses (ie, biconvex toric aspheric optic, symmetric biconvex diffractive optic, and biconvex diffractive aspheric toric) and asked to indicate their willingness to accept (for patients) or suggest (for surgeons) each lens. Acceptance was assessed assuming there was either no co-payment or co-payments of €500 to €1,500 +15%. RESULTS: All three lenses were widely accepted by patients, with 68% to 99% indicating acceptance when there was no co-payment. In contrast, surgeons’ willingness to suggest them was markedly lower (20% to 43%). Both patients’ acceptance of the lenses and surgeons’ willingness to suggest them decreased with increasing co-payment levels to 19% to 74% (patients) and 5% to 31% (surgeons) at the highest co-payment levels. CONCLUSIONS: There is a marked discrepancy between patients’ acceptance of the three lenses and surgeons’ willingness to suggest them. Although patients’ acceptance is high, it decreases with increasing out-of-pocket expenditure. Manufacturers should communicate the relative benefits and costs of their lenses to both surgeons and patients. [ J Refract Surg. 2014;30(4):278–281.]

The objective of the present study was to determine the effect of gastrojejunal tube (GJT) feedings in children with neurologic impairment (NI) on gastroesophageal reflux disease (GERD)- and/or dysfunctional swallowing-related visits and their associated costs.The present study is a retrospective cohort study of children with NI and GERD who underwent GJT placement at the study hospital from December 1999 to October 2006. Visits (emergency department, radiology, and hospitalizations) were reviewed from the time of birth until 1 year following GJT placement and classified as either not GERD and/or dysfunctional swallowing related or GERD and/or dysfunctional swallowing related (eg, pneumonias). Incident rate ratios (IRRs) were calculated by dividing the post-GJT visit rate by the pre-GJT visit rate. Other outcomes included associated costs, fundoplications, and deaths.Thirty-three patients met inclusion criteria. The IRR for total visits was 1.78 (95% confidence interval [CI] 1.12-2.81) and for GERD- and/or dysfunctional swallowing-related visits 2.88 (95% CI 1.68-4.94). Feeding tube-related visits (IRR 5.36, 95% CI 2.73-10.51) accounted for the majority. GERD- and/or dysfunctional swallowing-related costs per child per year were low overall, with no difference from pre-GJT versus post-GJT placement ($1851 vs $4601, P = 0.89). Seven (21%) children underwent Nissen fundoplication and 4 (12%) died within 1 year of GJT placement. Two deaths involved jejunal perforation.Children with NI and GERD who are treated with GJT feedings have significantly more GERD- and/or dysfunctional swallowing-related visits in the following year. The majority of these visits are because of the procedural complications, which are inexpensive. There is, however, mortality associated with the GJT and some children proceed to a fundoplication.

A recent systematic review and meta-analysis of the incidence and prevalence of schizophrenia and other psychoses in England investigated the variation in the rates of psychotic disorders. However, some of the questions of interest, and the data collected to answer these, could not be adequately addressed using established meta-analysis techniques. We developed a novel statistical method, which makes combined use of fractional polynomials and meta-regression. This was used to quantify the evidence of gender differences and a secondary peak onset in women, where the outcome of interest is the incidence of schizophrenia. Statistically significant and epidemiologically important effects were obtained using our methods. Our analysis is based on data from four studies that provide 50 incidence rates, stratified by age and gender. We describe several variations of our method, in particular those that might be used where more data is available, and provide guidance for assessing the model fit. Copyright © 2013 John Wiley & Sons, Ltd.

Background The purpose of this study was to determine precipitation limits and construct curves for calcium and phosphorus in parenteral nutrition solutions compounded with specialty amino acid solutions. Methods The effect of temperature, concentration of amino acids, and pH on the solubility of calcium and phosphate was studied for two specialized amino acid solutions: NephrAmine and HepatAmine. Ten amino acid solutions were manufactured with NephrAmine and 12 with HepatAmine at amino acid concentrations of 0.8%, 1.5%, and 2%. The final dextrose concentration was 10%. Some of the solutions were tested with the additive cysteine hydrochloride, 40 mg cysteine/g of protein, and some were buffered with sodium bicarbonate or hydrochloric acid to model the pH of a combined fat emulsion and total parenteral nutrient (TPN) solution. Calcium gluconate and potassium phosphate were added to test samples of each TPN solution. A range of calcium concentrations of 2.5 to 40 mEq/L and phosphate concentrations of 2.5 to 40 mmol/L were tested. After storage at room temperature (25 degrees C) for 18 hours, solutions were inspected for precipitation. At the end of the 18-hour period, the solutions were held in a water bath at 37 degrees C for 30 minutes and inspected for precipitation and microcrystallization. Results Solubility curves were plotted to represent Ca-PO4 solubility limits before visual or microscopic precipitation. These curves depend on the variables of time, temperature, concentration, and pH. Conclusions These data and graphs will help the clinical pharmacist estimate Ca-PO4 solubility limits and prevent precipitation of TPN solutions formulated with NephrAmine or Hepatamine.

PURPOSE: To evaluate uncorrected distance visual acuity (UDVA) as well as uncorrected near visual acuity (UNVA) as outcomes in treating presbyopic cataract patients to assist clinicians and ophthalmologists in their decision-making process regarding available interventions. METHODS: Medline, Embase, and Evidence Based Medicine Reviews were systematically reviewed to identify studies reporting changes in UDVA and UNVA after cataract surgery in presbyopic patients. Strict inclusion/exclusion criteria were used to exclude any studies not reporting uncorrected visual acuity in a presbyopic population with cataracts implanted with multifocal intraocular lenses (IOLs). Relevant outcomes (UDVA and UNVA) were identified from the studies retrieved through the systematic review process. RESULTS: Twenty-nine studies were identified that reported uncorrected visual acuities, including one study that reported uncorrected intermediate visual acuity. Nine brands of multifocal IOLs were identified in the search. All studies identified in the literature search reported improvements in UDVA and UNVA following multifocal IOL implantation. The largest improvements in visual acuity were reported using the Rayner M-Flex lens (Rayner Intraocular Lenses Ltd) (UDVA, binocular: 1.05 logMAR, monocular: 0.92 logMAR; UNVA, binocular and monocular: 0.83 logMAR) and the smallest improvements were reported using the Acri.LISA lens (Carl Zeiss Meditec) (UDVA, 0.21 decimal; UNVA, 0.51 decimal). CONCLUSIONS: The results of this systematic review show the aggregate of studies reporting a beneficial increase in UDVA and UNVA with the use of multifocal IOLs in cataract patients with presbyopia, hence providing evidence to support the hypothesis that multifocal IOLs increase UDVA and UNVA in cataract patients.

BACKGROUND AND PURPOSE: Improved selection of patients with stroke for IV tPA treatment may enhance clinical outcomes. Given the limited availability of MR imaging in hospitals, we examined the cost-effectiveness of adding CTP to the usual CT-based methods for selecting patients on the basis of the presence and extent of penumbra. MATERIALS AND METHODS: A decision-analytic model estimated the costs and outcomes associated with penumbra-based CTP selection in a patient population similar to that enrolled in the IV tPA clinical trials. Model inputs were obtained from published literature, clinical trial data, standard US costing sources, and expert opinion. Cost per life-year saved and cost per QALY gained were estimated from a hospital perspective. RESULTS: Addition of penumbra-based CTP to standard unenhanced CT improved favorable outcome (mRS, ≤1) by 0.59% and reduced cost by $42 compared with selection based on unenhanced CT alone. Life-years and QALYs improved. Multivariate sensitivity analysis predicted cost-effectiveness (≤$50,000 per QALY) in 89.2% of simulation runs. CONCLUSIONS: Using penumbra-based CTP after routine CT to select patients with ischemic stroke for IV tPA is cost-effective compared with the usual CT-based methods for hospitals. With the ease of access of CTP, penumbra-based selection methods may be readily available to hospitals. Thus, this economic analysis may lend further support to the consideration of a paradigm shift in acute stroke evaluation. CI : confidence interval CTP : perfusion CT DWI : diffusion-weighted imaging ECASS : European Cooperative Acute Stroke Study ED : emergency department FDA : US Food and Drug Administration Hrs : hours ICD-9 : international classification of diseases, 9th revision ICH : intracranial hemorrhage IV : intravenous IV tPA : intervenous tissue plasminogen activator mRS : modified Rankin Scale PWI : perfusion-weighted imaging QALY : quality-adjusted life-year SAH : subarachnoid hemorrhage SICH : symptomatic intracerebral hemorrhage

CME EDUCATIONAL OBJECTIVES 1. Discuss the common signs and symptoms of dysphagia and gastroesophageal reflux disease (GERD) in children with neurological impairment. 2. Formulate initial management options for dysphagia and GERD in children with neurological impairment. 3. Describe the serious sequelae associated with dysphagia and GERD in children with neurological impairment.

Current literature supports iron dextran as the only iron preparation compatible with parenteral nutrition (PN). Iron sucrose has been used for iron replacement therapy because of its lower rate of adverse events. The purpose of this study is to determine the physical and chemical stability of iron sucrose in PN.Physical and chemical stability of iron sucrose in nonlipid PN solutions (PN 1 for neonates and PN 2 for patients weighing20 kg) is tested over time in triplicate. Physical stability is determined by visually inspecting each PN solution for particulate matter and by filtering and analyzing each aliquot quantitatively for crystal precipitates. Chemical stability is confirmed if the iron concentrations by mass spectrometry remain within United States Pharmacopeia (USP) standards.Visual clarity is maintained in all PN solutions at hours 0 through 4. PN solution 1 remains clear for hours 8 through 24, whereas PN solution 2 shows an increase in particulate matter by 8 hours. All PN solutions 2 are considered visually incompatible by hour 24. Physical stability of iron sucrose for PN solutions 1 and 2 from hours 0 to 4 is within the USP guidelines for crystalline particulate matter. At hour 24, only solution 1 remains within USP guidelines. Chemical stability data indicate that iron concentrations are maintained throughout the 24-hour time period.The physical stability of iron sucrose in PN is time and concentration dependent. Concentrations0.25 mg/dL showed increasing particulate and should not be added to PN. However, iron sucrose is chemically stable in PN solutions.