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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.

BACKGROUND AND OBJECTIVES The literature suggests that the enzyme nitric oxide synthase (NOS) plays an important role in both periodontal disease (PD) and orofacial pain (OP), although few studies associate these two conditions simultaneously. The objective of this study was to evaluate the expression of the NOS enzyme in PD and OP, in comparison to those patients who did not present PD and/or OP. CONTENTS Seven electronic databases (Pubmed, Web of science, Scopus, Cochrane Library, BBO, LILACS, Clinical trial) were used to identify the potentially relevant studies published until April 2021. The research resulted in 1,960 studies, of which 11 were selected to be critically evaluated. Two independent reviewers selected titles and abstracts using the criteria defined in the PECO question (Population, Exposure, Comparison, Outcome). The methodological evaluation of the selected studies was carried out according to the Effective Public Health Practice Project (EPHPP). CONCLUSION: Scientific evidence demonstrated that NOS may play a key role in the pathogenesis of PD and OP, since its expression is increased in patients with these conditions. However, genetic studies on endothelial nitric oxide synthase (eNOS) gene mutations in patients with migraine and cluster headache did not indicate the expected susceptibility to pain. In addition, studies on the association of NOS expression in PD and OP, occurring simultaneously, are scarce. This review may support future research on NOS in two very common correlated diseases such as PD and OP. RESUMO JUSTIFICATIVA E OBJETIVOS A literatura sugere que a enzima óxido nítrico sintase (NOS) desempenha um papel importante tanto na doença periodontal (DP) quanto na dor orofacial (DOF), embora poucos estudos associem estas duas condições simultaneamente. O objetivo deste estudo foi analisar a expressão da NOS em pacientes com DP e DOF em comparação a controles sem estas condições. CONTEÚDO Foram consultadas as bases de dados eletrônicas (Pubmed, Web of Science, Scopus, Cochrane Library, BBO, Lilacs e Clinical Trial) para identificar os estudos potencialmente relevantes publicados até abril de 2021. As pesquisas resultaram em 1.960 estudos, dos quais 11 foram selecionados para serem avaliados criticamente. Os critérios definidos na questão PECO (População, Exposição, Comparação e Desfecho) foram usados para selecionar títulos e resumos por dois revisores independentes. A avaliação metodológica dos estudos selecionados foi realizada de acordo com a ferramenta Effective Public Health Practice Project (EPHPP). CONCLUSÃO As evidências científicas demonstraram que a NOS desempenha um importante papel na patogênese da DP e da DOF, já que sua expressão está aumentada em pacientes com estas condições. Porém, estudos genéticos sobre mutações dos genes do óxido nítrico sintase endotelial (eNOS) em pacientes com migrânea e cefaleia em salvas não evidenciaram a esperada suscetibilidade a dor. Além disso, estudos sobre a associação da expressão da NOS na DP e na DOF, ocorrendo simultaneamente, são escassos. Este estudo pode subsidiar futuras pesquisas sobre NOS na correlação de duas doenças muito frequentes como a DP e a DOF.

In the United Kingdom, significant changes have occurred in the Paralympic media production environment and style of Paralympic broadcasting. Given the generative nature of media texts on cultural representation, the authors explore the circulation of disability narratives in contemporary Paralympic media coverage. Drawing on an integrated data set that brings together textual analysis and audience perceptions, the authors highlight the presence of three disability narratives, termed: extraordinary normalcy, ableist rehabilitation, and sporting ablenationalism. The authors unpack the ways these three narratives differ from the widely and commonly used “supercrip” critique and discuss the implications of these narratives, and the wider cultural discourses and dialogue they generate, in terms of inclusion/exclusion and progressive social change.

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.

Objectives:While opioids temporarily alleviate pain, the overshoot of balancing pain drivers may increase pain, leading to opioid induced hyperalgesia (OIH). Our goal was to find out what chronic opioid treatment does to pain tolerance as measured by the cold pressor test (CPT), an objective measure of pain tolerance, and to find an alternative effective treatment for chronic pain and FM.Materials and Methods:The setting was an academic addiction medicine service that has an embedded pain service. Patients had routine clinical care starting with an evaluation that included assessment of medical and psychiatric conditions. Participants were 55 patients with OIH and 21 patients with fibromyalgia; all had at least two CPTs. Treatment included a single dose of buprenorphine for detoxification. In this open-label case series, patients were treated with low dose naltrexone (LDN), a pure opioid receptor antagonist that, we hypothesize, treats OIH and FM by restoring endogenous opioid tone.Results:Comparing initial and last CPT times, those with OIH more than quadrupled their pain tolerance, and those with FM doubled theirs. This improved pain tolerance for OIH and FM was statistically significant (p< 0.0001 andp= 0.003, respectively) and had a large effect size (r= 0.82 andr= 0.63, respectively).Discussion:Results suggest that patients on chronic opioid therapy should have pain tolerance measured by CPT with detoxification and LDN provided to correct opioid induced hyperalgesia if found. FM may also be treated with LDN. The main limitation of the findings was lack of a randomized control group treated with placebo.

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.

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.

Standard methods for the detection of carbamate pesticides are expensive, time-consuming, and require highly trained employees. Thus, electroanalytical methods are considered to be rapid, simple and low-cost alternatives. Here, we develop sensitive voltammetric methods for the determination of methomyl (a carbamate pesticide) using a bare boron-doped diamond electrode, square wave voltammetry (SWV), differential pulse voltammetry (DPV) and Britton–Robinson buffer (pH 2.0) as supporting electrolyte. Methomyl has three oxidation processes: meantime process P1 was chosen for the analytical determination due to its higher sensitivity in comparison with other processes. The detection limits and concentration ranges of the SWV and DPV methods were 1.9 × 10− 5 and 1.2 × 10− 6 mol L− 1, and 6.6–42.0 × 10− 5 to 5.0–410.0 × 10− 6 mol L− 1, respectively. The proposed methods were successfully applied in river water, tap water and commercial formulations showcasing > 80% mean recoveries. Comparing the two techniques, DPV was seen as the most sensitive method.

The 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 undertook proteomic profiling of Sengers patient fibroblasts and an AGKKO cell line to map the proteomic changes that ensue upon AGK dysfunction. This uncovered extensive remodelling of mitochondrial one-carbon metabolism enzymes and showed that inner membrane serine transporters, Sideroflexins (SFXNs), are novel substrates of the TIM22 complex. Deletion of SFXN1 recapitulates the remodelling of one-carbon metabolism observed in Sengers patient cells. Proliferation of cells lacking AGK is perturbed in the absence of exogenous serine and rescuable through addition of formate, highlighting the dysregulation of one carbon metabolism as a key molecular feature in the biology of Sengers syndrome.

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.

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.

The Health Education Thames Valley (HETV) Ophthalmology training programme holds compulsory weekly afternoon teaching sessions in Oxford. Traditionally, trainees travelled considerable distances to attend this teaching. Commuting is a known stress factor and car use has environmental, monetary and health costs. To reduce trainee costs, travelling time and improve teaching experience, we introduced an interactive and live video link across HETV. Teaching sessions were broadcast live using free videolink software between 3 sites. New hardware cost £200 per site. Attendees completed weekly feedback questionnaires on the videolink over 9 months. Over this period, the deanery had 22 trainees with 12 working outside Oxford. Projected annual travel savings were calculated. On average 10.8 trainees (49.1%) completed weekly questionnaires: 5.1 (range:3–8) were trainees working outside Oxford and 5.6 trainees (range 3–10) working in Oxford. Attendee responses showed on average: 78.6% learnt as much as attending in person; 91.17% felt interaction through the videolink was adequate; and 94.6% remained keen on telecommuting. Of the trainees in Oxford, 26.5% felt that the videolink interfered with the teaching session. The average videolink quality rating was 3.73 (1:poor; 5:excellent). Annually, the videolink will save each trainee working outside Oxford an average of 2120 kilometres in travel and £594 in expenses. Most attendees felt the videolink was a valuable tool in delivering teaching sessions. It eliminates unnecessary journeys and travel related stress. Within HETV, a £600 initial investment for new hardware would save trainees approximately £7128 annually. There is potential in expanding the role of the videolink to allow guest speakers worldwide to easily contribute to teaching sessions, eliminating unnecessary travel. This model could be adapted to postgraduate training programmes nationally to improve trainee wellbeing by reducing travelling time and costs.

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.

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.

Jake Jordan,1 Henry Dowson,2 Heather Gage,3 Daniel Jackson,3 Timothy Rockall4 1Health Economics Research Group, Brunel University, Uxbridge, Middlesex, England; 2Frimley Park Hospital, Surrey, England; 3School of Economics, University of Surrey, Surrey, England; 4Royal Surrey County Hospital, Surrey, England Background: Available evidence that compares outcomes from laparoscopic and open surgery for colorectal cancer shows no difference in disease free or survival time, or in health-related quality of life outcomes, but does not capture the short term benefits of laparoscopic methods in the early postoperative period. Aim: To explore the cost-effectiveness of laparoscopic colorectal surgery, compared to open methods, using quality of life data gathered in the first 6 weeks after surgery. Methods: Participants were recruited in 2006–2007 in a district general hospital in the south of England; those with a diagnosis of cancer or polyps were included in the analysis. Quality of life data were collected using EQ-5D, on alternate days after surgery for 4 weeks. Costs per patient, from a National Health Service perspective (in British pounds, 2006) comprised the sum of operative, hospital, and community costs. Missing data were filled using multiple imputation methods. The difference in mean quality adjusted life years and costs between surgery groups were estimated simultaneously using a multivariate regression model applied to 20 imputed datasets. The probability that laparoscopic surgery is cost-effective compared to open surgery for a given societal willingness-to-pay threshold is illustrated using a cost-effectiveness acceptability curve. Results: The sample comprised 68 laparoscopic and 27 open surgery patients. At 28 days, the incremental cost per quality adjusted life year gained from laparoscopic surgery was £12,375. At a societal willingness-to-pay of £30,000, the probability that laparoscopic surgery is cost-effective, exceeds 65% (at £20,000 ≈60%). In sensitivity analyses, laparoscopic surgery remained cost-effective compared to open surgery, provided it results in a saving ≥£699 in hospital bed days and takes no more than 8 minutes longer to perform. Conclusion: The study provides formal evidence of the cost-effectiveness of laparoscopic approaches and supports current guidelines that promote use of laparoscopy where suitably trained surgeons are available. Keywords: colorectal cancer, laparoscopy, cost-effectiveness, QALYs

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.

Aim Cost has been perceived to be a factor limiting the development of laparoscopic colorectal surgery. This study aimed to compare the costs of laparoscopic and open colorectal surgery. Method Patients undergoing laparoscopic or open elective colorectal surgery were recruited into a prospective study to evaluate the healthcare costs of each operative procedure in a district general hospital in England. All healthcare resources used (operation, hospital and community) were recorded and converted to costs in British pounds, 2006–2007. Costs of laparoscopic and open surgery were compared. Results In all, 201 consecutive patients consented and were recruited (131 laparoscopic, 70 open). Operative costs were greater in the laparoscopic group (£2049 vs£1263, P

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.

Fragestellung: Ziel dieser Studie war, ein systematisches Review und eine Metaanalyse der Kurz- und Langzeitergebnisse der Staplerhamorrhoidopexie durchzufuhren. Patienten und Methodik: Mit einer Literatursuche wurden randomisierte, kontrollierte Studien zum Vergleich von Staplerhamorrhoidopexie und Milligan-Morgan-/ Ferguson-Hamorrhoidektomie abgefragt. Die Daten wurden fur jede Studie einzeln entnommen und die Unterschiede mit Fixed- und Random-Effects-Modellen analysiert. Ergebnisse: Es wurden 34 randomisierte Studien und zwei systematische Reviews gefunden; hiervon wurden 29 Studien eingeschlossen. Die Staplerhamorrhoidopexie erwies sich in Bezug auf den Klinikaufenthalt (p < 0,001) als statistisch signifikant uberlegen und hinsichtlich der postoperativen Schmerzen (perioperativ und fruh-postoperativ), der Operationsdauer sowie der Blutungen (postoperativ und spat-postoperativ) als numerisch uberlegen. Nach der Staplerhamorrhoidopexie waren Prolapsrezidive und wiederholte Eingriffe aufgrund von Rezidiven haufiger. Bei den Komplikationsraten wurden keine Unterschiede beobachtet. Schlussfolgerung: Die Staplerhamorrhoidopexie reduziert die Dauer des Krankenhausaufenthalts und konnte einen Vorteil im Sinne einer kurzeren Operationsdauer, weniger postoperativer Schmerzen und geringerer Blutungen bieten, ist jedoch mit einer erhohten Rate von Prolapsrezidiven assoziiert.

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.

Background The authors conducted two pilot studies that investigated the roles of hypnotizability, absorption (defined as the ability to maintain focused attention on a task or stimulus) and state versus trait anxiety as predictors of dental anxiety. One of the studies also examined the effectiveness of hypnosis in managing dental anxiety. Methods Participants in study 1 completed measures of hypnotizability and anxiety, viewed a video of a dental procedure either under hypnosis or not, and completed dental anxiety questionnaires. Participants in study 2 were told either that the video showed major dental work or a routine polishing. All subjects watched the video and then completed measures assessing their perceptions of the video and their anxiety. Results The authors found a positive relationship between hypnotizability and scores on the Dental Anxiety Scale (DAS) ( F 1,290 = 3.45, P = .06), as well as an interaction between hypnotizability and hypnosis ( F 1,290 = 6.55, P = .01). An analysis of covariance found a relationship between trait and dental anxiety ( F 1,290 = 11.50; P = .001). A two-way analysis of variance found a main effect for hypnosis ( F 1,290 = 3.20, P = .07). The authors found an effect for group on the DAS ( F 1,228 = 3.67, P = .057), such that subjects in the negative-cognition group scored higher on the DAS. The authors found an interaction between absorption and cognition in perceptions of pain experienced by the patient in the video ( F 1,228 = 3.70, P = .05) and in ratings of one's own pain level if in the same situation ( F 1,228 = 4.38, P Conclusions Hypnotizability or absorption, pre-existing anxiety and cognitions about dental procedures predict dental anxiety, and hypnosis may be helpful for some, but not all, patients. Clinical Implications Characteristics such as hypnotizability, trait anxiety and negative cognitions predict which people develop dental anxiety and who will be more responsive to hypnosis. The authors provide suggestions for dentists treating anxious 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.

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.

A 7 year old boy injured his right eye while riding a bicycle. The handlebar was presumed to have impacted the globe resulting in gouging contusion injury. He presented with extensive soft tissue damage to the eye and orbit. The eye was proptosed with marked restriction of …

One active area of research in smart grid security focuses on applying game-theoretic frameworks to analyze interactions between a system and an attacker and formulate effective defense strategies. In previous work, a Nash equilibrium (NE) solution is chosen as the optimal defense strategy, which [7, 9] implies that the attacker has complete knowledge of the system and would also employ the corresponding NE strategy. In practice, however, the attacker may have limited knowledge and resources, and thus employ an attack which is less than optimal, allowing the defender to devise more efficient strategies. We propose a novel approach called an adaptive Markov Strategy (AMS) for defending a system against attackers with unknown, dynamic behaviors. The algorithm for computing an AMS is theoretically guaranteed to converge to a best response strategy against any stationary attacker, and also converge to a Nash equilibrium if the attacker is sufficiently intelligent to employ the AMS to launch the attack. To evaluate the effectiveness of an AMS in smart grid systems, we study a class of data integrity attacks that involve injecting false voltage information into a substation, with the goal of causing load shedding (and potentially a blackout). Our preliminary results show that the amount of load shedding costs can be significantly reduced by employing an AMS over a NE strategy.

Purpose Carnitine is a carrier molecule transporting long-chain fatty acids (LCFAs) into the mitochondria for fatty acid β-oxidation. The purpose of this study is to evaluate the role of carnitine supplementation in parenteral nutrition (PN) within the pediatric population. Our goal was to determine a weight range for which empiric carnitine supplementation is justified and to determine a weight range at which a carnitine level should first be drawn to confirm a deficiency prior to supplementation. Secondarily, we tried to determine a relationship among carnitine deficiency, hypoglycemia, and hypertriglyceridemia. Methods This was a retrospective observational study to evaluate 2 groups of pediatric patients (weighing 0.68 kg to 60 kg) who were NPO and receiving PN. The first group of patients ( n = 454) received carnitine supplementation (15 mg/kg/day) upon initiation of PN. The second group ( n = 299) did not receive carnitine supplementation until they were determined to have a carnitine deficiency. Results The data indicated that 82% of the patients weighing less than 5 kg were deficient. Patients weighing more than 5 kg had serum carnitine levels within the normal range. Therefore, patients receiving PN and weighing less than 5 kg should be supplemented with carnitine. Comparison of triglyceride, glucose, and carnitine showed no statistically significant difference ( P = .1936). Conclusion Patients weighing more than 5 kg should have serum carnitine levels drawn within 7 days to determine whether supplementation is needed. There is no statistical correlation among carnitine deficiency, hypoglycemia, and hypertriglyceridemia.

Ordering parenteral nutrition (PN) that is nutritionally appropriate, pharmacy acceptable, and physically compatible can be complex and time consuming. The Nutrition Support Service at Primary Children's Medical Center has developed a user-friendly, single-screen computer program for prescribing individualized PN orders for pediatric patients based on weight and nutrient requirements. Educational windows define dosage guidelines and unacceptable parameters. An internal surveillance process identifies incompatibilities resulting from calcium and phosphate concentrations, fluid restrictions, dosages, and cation and anion imbalances. An incompatible solution is prevented and corrected before it is compounded. The completed PN order generates a medical order, pharmacy order documentation sheet, compounding document, and label. The stored PN order interfaces directly with an automated system for compounding without physical manipulation. The computerized worksheet enhances efficient ordering of individualized ...

Previous studies in hepatocyte-derived cell lines and the whole liver established that the aryl hydrocarbon receptor (AhR) can disrupt G1-phase cell cycle progression following exposure to persistent AhR agonists, such as TCDD (dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin). Growth arrest was attributed to inhibition of G1-phase cyclin-dependent kinase 2 (CDK2) activity. The present study examined the effect of TCDD exposure on liver regeneration following 70% partial hepatectomy in mice lacking the Cip/Kip inhibitors p21(Cip1) or p27(Kip1) responsible for regulating CDK2 activity. Assessment of the regenerative process in wild-type, p21(Cip1) knockout, and p27(Kip1) knockout mice confirmed that TCDD-induced inhibition of liver regeneration is entirely dependent on p21(Cip1) expression. Compared with wild-type mice, the absence of p21(Cip1) expression completely abrogated the TCDD inhibition, and accelerated hepatocyte progression through G1 phase during the regenerative process. Analysis of the transcriptional response determined that increased p21(Cip1) expression during liver regeneration involved an AhR-dependent mechanism. Chromatin immunoprecipitation studies revealed that p21(Cip1) induction required AhR binding to the newly characterized nonconsensus xenobiotic response element, in conjunction with the tumor suppressor protein Kruppel-like factor 6 functioning as an AhR binding partner. The evidence also suggests that AhR functionality following partial hepatectomy is dependent on a p21(Cip1)-regulated signaling process, intimately linking AhR biology to the G1-phase cell cycle program.

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.]