Reduced toxicity of F-deficient Sendai virus vector in the mouse fetus

Current concerns over insertional mutagenesis by retroviral vectors mitigate investigations into alternative, potentially persistent gene therapy vector systems not dependent on genomic integration, such as Sendai virus vectors (SeVV). Prenatal gene therapy requires efficient gene delivery to several tissues, which may not be achievable by somatic gene transfer to the adult. Initially, to test the potential and tropism of the SeVV for gene delivery to fetal tissues, first-generation (replication- and propagation-competent) recombinant SeVV, expressing beta-galactosidase was introduced into late gestation immunocompetent mice via the amniotic and peritoneal cavities and the yolk sac vessels. At 2 days, this resulted in very high levels of expression particularly in the airway epithelium, mesothelium and vascular endothelium, respectively. However, as expected, substantial vector toxicity was observed. The efficiency of gene transfer and the level of gene expression were then examined using a second-generation SeVV. The second generation was developed to be still capable of cytoplasmic RNA replication and therefore high-level gene expression, but incapable of vector spread due to lack of the gene for viral F-protein. Vector was introduced into the fetal amniotic and peritoneal cavities, intravascularly, intramuscularly and intraspinally; at 2 days, expression was observed in the airway epithelia, peritoneal mesothelia, unidentified cells in the gut wall, locally at the site of muscle injection and in the dorsal root ganglia, respectively. Mortality was dramatically diminished compared with the first-generation vector.     

Psychological trauma in a relief worker--a case report from earthquake-struck areas of north Pakistan

Vicarious traumatization is now a well-known entity and may have negative influences on those that are involved in rescue efforts in any disaster or traumatic events. Healthcare workers work with trauma survivors and witness an immense array of gruesome and ghastly images. This work has the potential to cause those engaged in rescue efforts to become affected subconsciously. Job-related stress may cause psychological symptoms in care providers who provide support and listen to the survivors' account of trauma. A therapist working in disaster situations may become a victim of psychological anguish--undermining their physical and mental well-being as well as their profession, adversely affecting their traumatized patients, and leading to a counter-productive therapist-survivor relationship. This significant theme of secondary trauma must be recognized in relief workers at early stages and must be addressed at an individual as well as organizational level. The key may lie in turning to social supports, adapting positive coping mechanisms, and subsequently seeking mental health consultation. Further research is required in this area to determine the best resolution.     

A photopolymerized antimicrobial hydrogel coating derived from epsilon-poly-L-lysine

Hydrogels made from epsilon-poly-l-lysine-graft-methacrylamide (EPL-MA) have been found to have impressive wide spectrum antimicrobial activity against both bacteria (specifically Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens and Staphylococcus aureus) and fungi (specifically Candida albicans and Fusarium solani). The EPL-MA hydrogel also possesses in vitro biocompatibility and EPL-MA solution is relatively non-hemolytic: the concentration needed for onset of human red blood cell (hRBC) hemolysis is 12,500 μg/mL so that the selectivity for the pathogenic microorganisms over hRBCs is 230-1560. Further, EPL-MA hydrogel can be conveniently ultraviolet-immobilized onto plasma-treated plastic surfaces to form thin highly adherent antimicrobial hydrogel coatings for medical devices and implants.     

Regional determination of oxygen uptake in rodent lungs using hyperpolarized gas and an analytical treatment of intrapulmonary gas redistribution

A method is presented which allows for the accurate extraction of regional functional metrics in rodent lungs using hyperpolarized gas. The technique is based on the combination of measured T(1) decay, an independent measure of specific ventilation and mass balance considerations to extract the regional oxygen levels and uptake. In phantom and animal experiments, it is demonstrated that the redistribution of gas during the measurement is a significant confounding factor, and this effect is addressed analytically. The resulting parameterization of gas flow increases the accuracy of oxygen-sensitive MRI, and may also be used independently to assess air trapping and airway constriction. Limitations of the technique with respect to spatial resolution and robustness are also discussed.     

The brain in children: is contrast enhancement really needed after obtaining normal unenhanced CT results?

PURPOSE: To retrospectively determine and compare the sensitivity and specificity of unenhanced and contrast material-enhanced computed tomography (CT) (reference standard) in the diagnosis of brain abnormalities and to evaluate any change in diagnosis that resulted from the contrast-enhanced study. MATERIALS AND METHODS: This study was approved by the local research ethics board; the requirement for informed consent was waived. The authors reviewed the unenhanced and contrast-enhanced CT scans of the brain obtained in 353 children for indications other than trauma. There were 196 boys and 157 girls aged 0 months to 17.8 years. Scans were read independently by two pediatric neuroradiologists who were blinded to clinical information. The diagnosis for each scan was recorded according to the anatomic section (supratentorial, infratentorial, ventricles, and skull). The final diagnosis was classified as normal, abnormal, or equivocal. kappa Statistics, with 95% confidence intervals, were reported, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Interreader agreement for different anatomic regions varied between good (kappa coefficient, 0.63) and very good (kappa coefficient, 0.88) for unenhanced and contrast-enhanced scans. Sensitivity, specificity, positive predictive value, and negative predictive value for unenhanced scans were 97%, 89%, 87%, and 97%, respectively. The use of contrast material led to a change in the original normal or equivocal diagnosis to an abnormal diagnosis for only five (2.7%) of the 183 normal unenhanced scans. CONCLUSION: Unenhanced CT of developing brains has high sensitivity and specificity in the diagnosis of pathologic findings. The use of intravenous contrast material after unenhanced CT of the brain in children did not change the diagnosis frequently.     

Application of biomedical informatics to chronic pediatric diseases: a systematic review

Background  

Chronic diseases affect millions of children worldwide leading to substantial disease burden to the children and their families as well as escalating health care costs. The increasing trend in the prevalence of complex pediatric chronic diseases requires innovative and optimal delivery of care. Biomedical informatics applications play an important role in improving health outcomes while being cost-effective. However, their utility in pediatric chronic diseases has not been studied in a comprehensive and systematic way. The objective of this study was to conduct a systematic review of the effects of biomedical informatics applications in pediatric chronic diseases.     

Sonographic Assessment of Renal Growth in Patients with Beckwith-Wiedemann Syndrome: The Beckwith-Wiedemann Syndrome Renal Nomogram

BACKGROUND:

Beckwith-Wiedemann syndrome is a disorder of somatic overgrowth. Evidence of kidney overgrowth is a diagnostic criterion that may be used to help identify those patients who are at the greatest risk of developing Wilms tumors. In such subjects, kidney size is typically larger than that of age-matched normal controls.

OBJECTIVE:

The purpose of our study was to generate a nomogram that could be used to measure renal dimensions in children with Beckwith-Wiedemann syndrome in a clinical setting.

MATERIALS & METHODS:

All of the Beckwith-Wiedemann syndrome patients followed at our institution from 1996 to 2004 were eligible for inclusion in our study. Renal length was measured with a curvilinear transducer and with the patient supine. Renal lengths were measured for both kidneys using real-time ultrasound for all patients. Their data were compared with those of age-matched controls reported in the 1984 study by Rosenbaum et al.

RESULTS:

Ninety-six children with Beckwith-Wiedemann syndrome were followed from 1996 to 2004. Forty-three of these patients met our criteria for inclusion in the study: 28 girls (65%) and 15 boys (35%). We identified a linear relationship between kidney length and patient age. No statistically significant differences in renal length were found between boys and girls (p=0.2153) or between the kidneys on either side of the body (p=0.9613).

CONCLUSION:

Our study provides a practical, simple renal growth chart that offers a reasonable, sensitive method for evaluating kidney size in children with Beckwith-Wiedemann syndrome.     

Perinatal gene transfer to the liver

The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect. Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first weeks or months of life is inevitable. Some diseases can be managed using conventional medicines whereas others are, as yet, untreatable. In this review we consider the application of early intervention gene therapy in neonatal and fetal preclinical studies. We appraise the tools of this technology, including lentivirus, adenovirus and adeno-associated virus (AAV)-based vectors. We highlight the application of these for a range of diseases including hemophilia, urea cycle disorders such as ornithine transcarbamylase deficiency, organic acidemias, lysosomal storage diseases including mucopolysaccharidoses, glycogen storage diseases and bile metabolism. We conclude by assessing the advantages and disadvantages associated with fetal and neonatal liver gene transfer.     

Family physicians' attitudes toward education in research skills during residency: findings from a national mailed survey

OBJECTIVE

To determine the attitudes of practising Canadian family physicians toward education in research skills during residency, to identify what determines these attitudes, and to investigate the effect of education in research skills on future research activity.

DESIGN

Mailed survey.

SETTING

Primary care.

PARTICIPANTS

Stratified random sample of 247 practising physicians who were members of the College of Family Physicians of Canada.

MAIN OUTCOME MEASURES

Physicians’ attitudes toward education in research skills during residency, their perceptions of the value of research in primary care, and their current involvement in research activities.

RESULTS

Overall response rate was 56%. Nearly all respondents agreed that critical appraisal skills are essential to the practice of modern family medicine. Most agreed that it is very important that the evidence base for primary care medicine be developed by family physicians, yet only one-third agreed that research skills ought to receive more emphasis during residency training, and fewer than one-quarter agreed that practising family physicians should have strong research skills. Fewer than half the respondents agreed that a core goal of family medicine residency training should be to promote and develop an active interest in research. While three-quarters agreed that research projects during residency can be formative learning experiences, only about 40% indicated that research projects should be required, and only about 20% considered their own resident research projects to have been highly influential learning experiences. Respondents whose residency programs had research in the curriculum were significantly more likely to have found their research projects to be highly influential learning experiences (P <.05), and those who had successfully completed research projects were less likely to believe that they lacked the necessary skills and expertise to conduct their own research studies. Those who had successfully completed resident research projects participated in postresidency research activity at a significantly higher rate than those who did not complete projects (P <.01).

CONCLUSION

Despite a conviction that research is important in primary care, only a few practising family physicians in our sample believed that strong research skills are important or that education in research skills should receive more emphasis during residency training. Resident research projects are not invariably influential learning experiences, although some evidence indicates that successful completion of a project makes future participation in research more likely.