EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis.

EMILIN1 (elastin-microfibril-interface-located-protein-1) is a structural component of the elastic fiber network and localizes to the interface between the fibrillin microfibril scaffold and the elastin core. How EMILIN1 contributes to connective tissue integrity is not fully understood. Here, we report bi-allelic EMILIN1 loss-of-function variants causative for an entity combining cutis laxa, arterial tortuosity, aneurysm formation, and bone fragility, resembling autosomal-recessive cutis laxa type 1B, due to EFEMP2 (FBLN4) deficiency. In both humans and mice, absence of EMILIN1 impairs EFEMP2 extracellular matrix deposition and LOX activity resulting in impaired elastogenesis, reduced collagen crosslinking, and aberrant growth factor signaling. Collagen fiber ultrastructure and histopathology in EMILIN1- or EFEMP2-deficient skin and aorta corroborate these findings and murine Emilin1-/- femora show abnormal trabecular bone formation and strength. Altogether, EMILIN1 connects elastic fiber network with collagen fibril formation, relevant for both bone and vascular tissue homeostasis.

Novel heterozygous mutation in the PTEN gene associated with ovarian germ cell tumor complicated by growing teratoma syndrome and overgrowth in a two-year-old female.

Growing teratoma syndrome (GTS) is a condition in which mature teratoma with negative tumor markers arises at the site of a treated malignant germ cell tumor. Pathogenic variants in PTEN have been reported to cause autosomal dominant cancer predisposition syndromes and are associated with germ cell tumors. We report the association of a novel heterozygous pathogenic variant in PTEN and very early onset ovarian germ cell tumor complicated by GTS as well as overgrowth syndrome. This marks the youngest reported patient to have developed GTS following treatment of her primary malignant ovarian germ cell tumor.

Neogenin Recruitment of the WAVE Regulatory Complex to Ependymal and Radial Progenitor Adherens Junctions Prevents Hydrocephalus.

Denudation of the ependyma due to loss of cell adhesion mediated by cadherin-based adherens junctions is a common feature of perinatal hydrocephalus. Junctional stability depends on the interaction between cadherins and the actin cytoskeleton. However, the molecular mechanism responsible for recruiting the actin nucleation machinery to the ependymal junction is unknown. Here, we reveal that loss of the netrin/RGM receptor, Neogenin, leads to severe hydrocephalus. We show that Neogenin plays a critical role in actin nucleation in the ependyma by anchoring the WAVE regulatory complex (WRC) and Arp2/3 to the cadherin complex. Blocking Neogenin binding to the Cyfip1/Abi WRC subunit results in actin depolymerization, junctional collapse, and denudation of the postnatal ventricular zone. In the embryonic cortex, this leads to loss of radial progenitor adhesion, aberrant neuronal migration, and neuronal heterotopias. Therefore, Neogenin-WRC interactions play a fundamental role in ensuring the fidelity of the embryonic ventricular zone and maturing ependyma.

Harnessing molecular motors for nanoscale pulldown in live cells.

Protein-protein interactions (PPIs) regulate assembly of macromolecular complexes, yet remain challenging to study within the native cytoplasm where they normally exert their biological effect. Here we miniaturize the concept of affinity pulldown, a gold-standard in vitro PPI interrogation technique, to perform nanoscale pulldowns (NanoSPDs) within living cells. NanoSPD hijacks the normal process of intracellular trafficking by myosin motors to forcibly pull fluorescently tagged protein complexes along filopodial actin filaments. Using dual-color total internal reflection fluorescence microscopy, we demonstrate complex formation by showing that bait and prey molecules are simultaneously trafficked and actively concentrated into a nanoscopic volume at the tips of filopodia. The resulting molecular traffic jams at filopodial tips amplify fluorescence intensities and allow PPIs to be interrogated using standard epifluorescence microscopy. A rigorous quantification framework and software tool are provided to statistically evaluate NanoSPD data sets. We demonstrate the capabilities of NanoSPD for a range of nuclear and cytoplasmic PPIs implicated in human deafness, in addition to dissecting these interactions using domain mapping and mutagenesis experiments. The NanoSPD methodology is extensible for use with other fluorescent molecules, in addition to proteins, and the platform can be easily scaled for high-throughput applications.

Effects of Age and Working Memory Capacity on Speech Recognition Performance in Noise Among Listeners With Normal Hearing.

OBJECTIVES: This study aimed to determine if younger and older listeners with normal hearing who differ on working memory span perform differently on speech recognition tests in noise. Older adults typically exhibit poorer speech recognition scores in noise than younger adults, which is attributed primarily to poorer hearing sensitivity and more limited working memory capacity in older than younger adults. Previous studies typically tested older listeners with poorer hearing sensitivity and shorter working memory spans than younger listeners, making it difficult to discern the importance of working memory capacity on speech recognition. This investigation controlled for hearing sensitivity and compared speech recognition performance in noise by younger and older listeners who were subdivided into high and low working memory groups. Performance patterns were compared for different speech materials to assess whether or not the effect of working memory capacity varies with the demands of the specific speech test. The authors hypothesized that (1) normal-hearing listeners with low working memory span would exhibit poorer speech recognition performance in noise than those with high working memory span; (2) older listeners with normal hearing would show poorer speech recognition scores than younger listeners with normal hearing, when the two age groups were matched for working memory span; and (3) an interaction between age and working memory would be observed for speech materials that provide contextual cues. DESIGN: Twenty-eight older (61 to 75 years) and 25 younger (18 to 25 years) normal-hearing listeners were assigned to groups based on age and working memory status. Northwestern University Auditory Test No. 6 words and Institute of Electrical and Electronics Engineers sentences were presented in noise using an adaptive procedure to measure the signal-to-noise ratio corresponding to 50% correct performance. Cognitive ability was evaluated with two tests of working memory (Listening Span Test and Reading Span Test) and two tests of processing speed (Paced Auditory Serial Addition Test and The Letter Digit Substitution Test). RESULTS: Significant effects of age and working memory capacity were observed on the speech recognition measures in noise, but these effects were mediated somewhat by the speech signal. Specifically, main effects of age and working memory were revealed for both words and sentences, but the interaction between the two was significant for sentences only. For these materials, effects of age were observed for listeners in the low working memory groups only. Although all cognitive measures were significantly correlated with speech recognition in noise, working memory span was the most important variable accounting for speech recognition performance. CONCLUSIONS: The results indicate that older adults with high working memory capacity are able to capitalize on contextual cues and perform as well as young listeners with high working memory capacity for sentence recognition. The data also suggest that listeners with normal hearing and low working memory capacity are less able to adapt to distortion of speech signals caused by background noise, which requires the allocation of more processing resources to earlier processing stages. These results indicate that both younger and older adults with low working memory capacity and normal hearing are at a disadvantage for recognizing speech in noise.

Vastus lateralis transfer for severe hip abductor deficiency: a salvage procedure.

INTRODUCTION: Abductor muscle deficiency can be a debilitating problem following hip arthroplasty surgery. We report outcomes of a novel method of abductor muscle function reconstruction surgery in patients with chronic, irreparable gluteus medius and minimus defects. PATIENTS AND METHODS: Four consecutive patients who underwent our method of abductor reconstruction surgery were retrospectively reviewed. All patients had severe pain and positive Trendelenberg gait before surgery. TECHNIQUE: the vastus lateralis (VL) muscle was raised on its neurovascular pedicle and transferred 12-14 centimetres by proximal translation. The proximal portion of VL was reattached via bony anchors to the external surface of the iliac wing just below the iliac crest. The distal portion of VL reattached to the lateral femoral shaft, lateral intermuscular septum, and the fascia of vastus intermedius. RESULTS: Average follow-up was 10 months (range 7-15 months). Three of the four patients report dramatic improvement in pain as measured by the visual analogue pain scale. The same three patients report being "extremely satisfied" with the pain relief achieved and "extremely satisfied" with the operation overall. Two patients reported being "extremely satisfied" with improvements in walking. Hip abduction power improved in all patients but to varying degrees. CONCLUSION: The results show that our method of VL transfer may be a viable option for patients with severe abductor deficiency. Modest but clinically relevant early results are seen.

RGMa regulates cortical interneuron migration and differentiation.

The etiology of neuropsychiatric disorders, including schizophrenia and autism, has been linked to a failure to establish the intricate neural network comprising excitatory pyramidal and inhibitory interneurons during neocortex development. A large proportion of cortical inhibitory interneurons originate in the medial ganglionic eminence (MGE) of the ventral telencephalon and then migrate through the ventral subventricular zone, across the corticostriatal junction, into the embryonic cortex. Successful navigation of newborn interneurons through the complex environment of the ventral telencephalon is governed by spatiotemporally restricted deployment of both chemorepulsive and chemoattractive guidance cues which work in concert to create a migratory corridor. Despite the expanding list of interneuron guidance cues, cues responsible for preventing interneurons from re-entering the ventricular zone of the ganglionic eminences have not been well characterized. Here we provide evidence that the chemorepulsive axon guidance cue, RGMa (Repulsive Guidance Molecule a), may fulfill this function. The ventricular zone restricted expression of RGMa in the ganglionic eminences and the presence of its receptor, Neogenin, in the ventricular zone and on newborn and maturing MGE-derived interneurons implicates RGMa-Neogenin interactions in interneuron differentiation and migration. Using an in vitro approach, we show that RGMa promotes interneuron differentiation by potentiating neurite outgrowth. In addition, using in vitro explant and migration assays, we provide evidence that RGMa is a repulsive guidance cue for newborn interneurons migrating out of the ganglionic eminence ventricular zone. Intriguingly, the alternative Neogenin ligand, Netrin-1, had no effect on migration. However, we observed complete abrogation of RGMa-induced chemorepulsion when newborn interneurons were simultaneously exposed to RGMa and Netrin-1 gradients, suggesting a novel mechanism for the tight regulation of RGMa-guided interneuron migration. We propose that during peak neurogenesis, repulsive RGMa-Neogenin interactions drive interneurons into the migratory corridor and prevent re-entry into the ventricular zone of the ganglionic eminences.

Impact of critical care telemedicine consultations on children in rural emergency departments.

OBJECTIVES: To compare the quality of care delivered to critically ill and injured children receiving telemedicine, telephone, or no consultation in rural emergency departments. DESIGN: Retrospective chart review with concurrent surveys. SETTING AND PARTICIPANTS: Three hundred twenty patients presenting in the highest triage category to five rural emergency departments with access to pediatric critical care consultations from an academic children's hospital. MEASUREMENTS AND MAIN RESULTS: Quality of care was independently rated by two pediatric emergency medicine physicians applying a previously validated 7-point implicit quality review tool to the medical records. Quality was compared using multivariable linear regression adjusting for age, severity of illness, and temporal trend. Referring physicians were surveyed to evaluate consultation-related changes in their care. Parents were also surveyed to evaluate their satisfaction and perceived quality of care. In the multivariable analysis, with the no-consultation cohort as the reference, overall quality was highest among patients who received telemedicine consultations (n=58; ß=0.50 [95% CI, 0.17-0.84]), intermediate among patients receiving telephone consultation (n=63; ß=0.12 [95% CI, -0.14 to 0.39]), and lowest among patients receiving no consultation (n=199). Referring emergency department physicians reported changing their diagnosis (47.8% vs 13.3%; p<0.01) and therapeutic interventions (55.2% vs 7.1%; p<0.01) more frequently when consultations were provided using telemedicine than telephone. Parent satisfaction and perceived quality were significantly higher when telemedicine was used, compared with telephone, for six of the seven measures. CONCLUSIONS: Physician-rated quality of care was higher for patients who received consultations with telemedicine than for patients who received either telephone or no consultation. Telemedicine consultations were associated with more frequent changes in diagnostic and therapeutic interventions, and higher parent satisfaction, than telephone consultations.

Hippocampal volume and cell density changes in a mouse model of human genetic epilepsy.

OBJECTIVE: The human γ-aminobutyric acid type A (GABAA)γ2R43Q (R43Q) mutation is associated with genetic epilepsy with febrile seizures. R43Q mice in the C57Bl/6J background do not display spontaneous seizures, but are significantly more susceptible to hyperthermic seizures, providing a model with enhanced seizure susceptibility without the confounding influence of ongoing epileptic activity. Because of GABA's role in brain development, we sought to determine whether the R43Q mutation alters brain structure before the appearance of seizures. METHODS: We used 16.4-tesla, high-field MRI to determine the volumes of hippocampal subregions. Histologic analysis of the same brains allowed stereology-based estimates of neuron counts to be obtained in CA1-3 and the dentate gyrus. RESULTS: Morphologic changes were evident in seizure-naive hippocampi of susceptible mice. Dentate granule cell MRI determined that volume was 5% greater in R43Q mice compared with controls (0.628 mm(3), 95% confidence interval [CI] 0.611-0.645 vs 0.595 mm(3), 95% CI 0.571-0.619). The dentate granule cell density was 30% higher in R43Q compared with control mice (553 × 10(3) cells/mm(3), 95% CI 489-616 vs 427 × 10(3) cells/mm(3), 95% CI 362-491). CONCLUSIONS: In a genetic epilepsy model that is both seizure-naive and carries an allele for febrile seizure susceptibility, we have determined hippocampal structural changes that may be applied as a biomarker for seizure susceptibility.

Rural inpatient telepharmacy consultation demonstration for after-hours medication review.

OBJECTIVE: Medication errors contribute to a significant number of fatal and nonfatal adverse medical events each year. Many actions, from both a policy and innovation standpoint, have been taken to reduce medication errors in the inpatient setting; yet, these actions often target larger urban hospitals. Rural hospitals face many more challenges in implementing these changes due to fewer resources and lower patient volumes. Our article discusses the implementation and results of a telepharmacy demonstration implemented between the University of California Davis Health System and six rural hospitals. MATERIALS AND METHODS: A retrospective chart review obtained baseline medication errors for comparison with the prospective review of medication orders through telepharmacy. Medication orders from rural hospitals were transmitted via fax to the University of California Davis Pharmacy for after-hours review. If a medication required after-hours removal from the pharmacy, it was requested that video verification by a telepharmacist be used to verify that the correct medication was removed from the pharmacy. RESULTS: Baseline findings from the retrospective chart review indicated that 30.0% of patients had one or more medication errors and that these errors occurred in 7.2% of the medication orders. None of these errors were found to have resulted in harm to the patients. During the telepharmacy demonstration, 2,378 medication orders were screened from 504 independent order review requests. In total, 58 (19.2%) patients had one or more medication errors. The errors from the telepharmacy demonstration represented potential errors that were identified through telepharmacy medication review. CONCLUSIONS: Telepharmacy represents a potential alternative to around-the-clock on-site pharmacist medication review for rural hospitals.

WiFi RFID demonstration for resource tracking in a statewide disaster drill.

OBJECTIVE: To investigate the capabilities of Radio Frequency Identification (RFID) tracking of patients and medical equipment during a simulated disaster response scenario. DESIGN: RFID infrastructure was deployed at two small rural hospitals, in one large academic medical center and in two vehicles. Several item types from the mutual aid equipment list were selected for tracking during the demonstration. A central database server was installed at the UC Davis Medical Center (UCDMC) that collected RFID information from all constituent sites. The system was tested during a statewide disaster drill. During the drill, volunteers at UCDMC were selected to locate assets using the traditional method of locating resources and then using the RFID system. RESULTS: This study demonstrated the effectiveness of RFID infrastructure in real-time resource identification and tracking. Volunteers at UCDMC were able to locate assets substantially faster using RFID, demonstrating that real-time geolocation can be substantially more efficient and accurate than traditional manual methods. A mobile, Global Positioning System (GPS)-enabled RFID system was installed in a pediatric ambulance and connected to the central RFID database via secure cellular communication. This system is unique in that it provides for seamless region-wide tracking that adaptively uses and seamlessly integrates both outdoor cellular-based mobile tracking and indoor WiFi-based tracking. CONCLUSIONS: RFID tracking can provide a real-time picture of the medical situation across medical facilities and other critical locations, leading to a more coordinated deployment of resources. The RFID system deployed during this study demonstrated the potential to improve the ability to locate and track victims, healthcare professionals, and medical equipment during a region-wide disaster.

Weight status of children and adolescents in a telepsychiatry clinic.

The prevalence of overweight and obesity is approximately 32% among children and adolescents in the United States. Comorbid conditions associated with pediatric overweight and obesity include psychiatric conditions. The purpose of this study was to determine the prevalence of overweight and obesity among children and adolescents presenting for consultation from rural communities to the UC Davis Telemedicine Program (UCDTP), as well as to collect preliminary data to design an integrated disease management program for children and adolescents with obesity and mental illness. Patients aged 21 and under seen for psychiatric consultation at the UCDTP between 2004 and 2006 were included. Retrospective medical record review was conducted to determine the major psychiatric diagnoses, height, weight, body-mass index, and weight status (underweight/at risk for underweight, normal weight, overweight, or obese) for each patient. Of the 230 patients referred, a total of 121 patients had both height and weight values documented. Three patients were underweight; 51 were normal weight; 28 were overweight; 39 were obese. The most common psychiatric diagnoses in the 121 patients were attention deficit/hyperactivity disorder (ADHD; n = 40), bipolar disorder (n = 36), and depression (n = 31). The most common psychiatric diagnoses in patients with available weight and height data who were overweight and obese were bipolar disorder (n = 20), depression (n = 18), and ADHD (n = 17). Approximately 55% of child and adolescent patients seen for telepsychiatry consultation whose charts documented height and weight measurements were overweight or obese. Psychiatric diagnoses in overweight youngsters need to be researched further to determine whether the weight change is primary or secondary to mood and/or to treatments, such as medication. At such a high rate of comorbidity, monitoring the weight status of young psychiatric patients in this population is indicated.

Netrin-1: diversity in development.

In 1990, the discovery of three Caenorhabditis elegans genes (unc5, unc6, unc40) involved in pioneer axon guidance and cell migration marked a significant advancement in neuroscience research [Hedgecock EM, Culotti JG, Hall DH. The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. Neuron 1990;4:61-85]. The importance of this molecular guidance system was exemplified in 1994, when the vertebrate orthologue of Unc6, Netrin-1, was discovered to be a key guidance cue for commissural axons projecting toward the ventral midline in the rodent embryonic spinal cord [Serafini T, Kennedy TE, Galko MJ, Mirzayan C, Jessell TM, Tessier-Lavigne M. The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6. Cell 1994;78:409-424]. Since then, Netrin-1 has been found to be a critical component of embryonic development with functions in axon guidance, cell migration, morphogenesis and angiogenesis. Netrin-1 also plays a role in the adult brain, suggesting that manipulating netrin signals may have novel therapeutic applications.

Quality of care of children in the emergency department: association with hospital setting and physician training.

OBJECTIVE: To investigate differences in the quality of emergency care for children related to differences in hospital setting, physician training, and demographic factors. STUDY DESIGN: This was a retrospective cohort study of a consecutive sample of children presenting with high-acuity illnesses or injuries at 4 rural non-children's hospitals (RNCHs) and 1 academic urban children's hospital (UCH). Two of 4 study physicians independently rated quality of care using a validated implicit review instrument. Hierarchical modeling was used to estimate quality of care (scored from 5 to 35) across hospital settings and by physician training. RESULTS: A total of 304 patients presenting to the RNCHs and the UCH were studied. Quality was lower (difference = -3.23; 95% confidence interval [CI] = -4.48 to -1.98) at the RNCHs compared with the UCH. Pediatric emergency medicine (PEM) physicians provided better care than family medicine (FM) physicians and those in the "other" category (difference = -3.34, 95% CI = -5.40 to -1.27 and -3.12, 95% CI = -5.25 to -0.99, respectively). Quality of care did not differ significantly between PEM and general emergency medicine (GEM) physicians in general, or between GEM and PEM physicians at the UCH; however, GEM physicians at the RNCHs provided care of lesser quality than PEM physicians at the UCH (difference = -2.75; 95% CI = -5.40 to -0.05). Older children received better care. CONCLUSIONS: The quality of care provided to children is associated with age, hospital setting, and physician training.

Clinical management and patient outcomes among children and adolescents receiving telemedicine consultations for obesity.

Rural residents report lower likelihood of exercising, and higher rates of obesity, heart disease, and diabetes compared to their urban counterparts. Our goals were to (1) investigate the outcomes of telemedicine consultations for pediatric obesity on changes/additions to diagnoses, diagnostic evaluation or treatment, and (2) determine whether changes in diagnostic and management recommendations made by the consultant were associated with improvements in patient nutrition, activity level, and weight. We conducted a retrospective medical record review of patients referred to a University-affiliated Children's Hospital Pediatric Telemedicine Weight Management Clinic for a diagnosis of obesity. Of the 139 children and adolescents who received pediatric weight management consultations during the study period, 99 patients met inclusion criteria. Weight management consultations resulted in changes/additions to diagnoses in 77.8% of patients and changes/additions to diagnostic evaluation in 79.8% of patients. Of patients seen more than once, 80.7% showed improvement in clinical outcomes. Of patients seen more than once, 80.6% improved their diet, 69.4% increased activity levels, 21.0% showed slowing of weight gain or weight maintenance, and 22.6% showed weight reduction. Improvements in clinical outcomes were not associated with changes/additions to diagnoses (Odds Ratio [OR] = 0.98; 95% Confidence Interval [CI] = 0.25-3.98) and were weakly associated with changes/additions to diagnostic evaluations (OR = 2.23; 95% CI = 0.58-8.73). However, changes/additions to treatment were associated with improvement in weight status (OR = 9.0; 95% CI = 1.34-76.21). Obesity consultations were associated with changes/additions to diagnoses, diagnostic evaluation, and treatment. Treatment changes were associated with improvement in weight status. Telemedicine weight management consultations have the potential to result in modifications in patient care plans and outcomes.

A new implicit review instrument for measuring quality of care delivered to pediatric patients in the emergency department.

BACKGROUND: There are few outcomes experienced by children receiving care in the Emergency Department (ED) that are amenable to measuring for the purposes of assessing of quality of care. The purpose of this study was to develop, test, and validate a new implicit review instrument that measures quality of care delivered to children in EDs. METHODS: We developed a 7-point structured implicit review instrument that encompasses four aspects of care, including the physician's initial data gathering, integration of information and development of appropriate diagnoses; initial treatment plan and orders; and plan for disposition and follow-up. Two pediatric emergency medicine physicians applied the 5-item instrument to children presenting in the highest triage category to four rural EDs, and we assessed the reliability of the average summary scores (possible range of 5-35) across the two reviewers using standard measures. We also validated the instrument by comparing this mean summary score between those with and without medication errors (ascertained independently by two pharmacists) using a two-sample t-test. RESULTS: We reviewed the medical records of 178 pediatric patients for the study. The mean and median summary score for this cohort of patients were 27.4 and 28.5, respectively. Internal consistency was high (Cronbach's alpha of 0.92 and 0.89). All items showed a significant (p < 0.005) positive correlation between reviewers using the Spearman rank correlation (range 0.24 to 0.39). Exact agreement on individual items between reviewers ranged from 70.2% to 85.4%. The Intra-class Correlation Coefficient for the mean of the total summary score across the two reviewers was 0.65. The validity of the instrument was supported by the finding of a higher score for children without medication errors compared to those with medication errors which trended toward significance (mean score = 28.5 vs. 26.0, p = 0.076). CONCLUSION: The instrument we developed to measure quality of care provided to children in the ED has high internal consistency, fair to good inter-rater reliability and inter-rater correlation, and high content validity. The validity of the instrument is supported by the fact that the instrument's average summary score was lower in the presence of medication errors, which trended towards statistical significance.

Hepatitis C videoconferencing: the impact on continuing medical education for rural healthcare providers.

This study compared the impact of multipoint videoconferencing (VC) versus standard lecturing (ST) on primary care providers' (MDs, NPs/PAs, and RNs) education regarding hepatitis C virus (HCV). The hypothesis was that the educational impact of teaching through telemedicine is comparable to the traditional method. The aim was to provide participants clinically relevant information and knowledge about the natural history, diagnosis, and management of HCV. Improved knowledge was scored from a 10-item quiz administered before and after the educational intervention. Comparison of the pretest knowledge scores within provider groups showed no statistically significant difference in baseline knowledge for the ST versus VC method. However, for all practitioners combined, the VC group scored significantly lower on the pretest than the ST group (p < 0.05). All three types of learners improved their knowledge scores following intervention. On average, MDs and NP/PAs correctly answered two to 3.5 more questions in the posttest. RNs showed the greatest improvements, correctly answering an average of four to five more questions following intervention. Improvement in knowledge scores between the two methods was statistically significant in favor of VC for the MDs (VC = 3.56 +/- 1.92 vs. ST = 2.13 +/- 1.89, p < 0.001) and all groups combined (VC 4.37 +/- 1.92 vs ST 3.06 +/- 1.89, p < 0.001). The results of this study indicate that VC is equivalent, if not better, than standard continuing medical education (CME). VC can potentially improve clinician education regarding the history, diagnosis, and management of HCV, thereby making a substantial impact on the clinical course of patients with this condition. In addition, VC has the potential to eliminate the financial and geographic barriers to professional education for rural practitioners.

Medication errors among acutely ill and injured children treated in rural emergency departments.

STUDY OBJECTIVE: We identify the incidence, nature, and consequences of medication errors among acutely ill and injured children receiving care in a sample of rural emergency departments (EDs). METHODS: Two pediatric pharmacists applied a medication error data collection instrument to the medical records of all critically ill children (highest triage category) treated in 4 northern California rural EDs between January 2000 and June 2003. Physician-related medication errors were defined as those involving wrong dose, wrong or inappropriate medication for condition, wrong route, or wrong dosage form. Wrong dose was determined by preset criteria, with doses above or below 10% to 25% of correct dose considered errors, depending on class of medication. Medication errors were classified into categories A through I under 3 broader categories, including errors having the potential to cause harm (A), errors that cause no harm (B to D), and errors that cause harm to the patient (E to I). RESULTS: Complete data were available from 177 (97.3%) of the 182 patients identified as having been triaged in the highest category during the study period. A total of 84 medication errors were identified among 69 patients, resulting in a medication error incidence of 39.0%. Twenty-four physician-related medication errors were identified among 21 patients, resulting in a physician-related medication error incidence of 11.9%. Among the 69 patients with medication errors, 11 had errors categorized as having the potential to cause harm (15.9%), and 58 had errors categorized as causing no harm (85.5%). CONCLUSION: We found a high incidence of medication errors and physician-related medication errors among the acutely ill and injured children presenting to rural EDs in northern California. None of the medication errors identified caused harm to the patients included in this study.

Neogenin: A multi-functional receptor regulating diverse developmental processes.

Neogenin, a close relative of the axon guidance receptor Deleted in Colorectal Cancer (DCC), has been shown to be a receptor for members of the Netrin and Repulsive Guidance Molecule (RGM) families. While Netrin-1-Neogenin interactions result in a chemoattractive axon guidance response, the interaction between Neogenin and RGMa induces a chemorepulsive response. Evidence is now accumulating that Neogenin is a multi-functional receptor regulating many diverse developmental processes, including neural tube and mammary gland formation, myogenesis and angiogenesis. Little is known of the function of Neogenin in the adult, however, a novel role in the regulation of iron homeostasis is now emerging. While the signal transduction pathways activated by Neogenin are poorly understood, it is clear that the functional outcome of Neogenin activation, at least in the embryo, depends on both the developmental context as well as the nature of the ligand.