A new polymer-based approach for in vivo transfection in postnatal brain.

BACKGROUND: Gene delivery within the central nervous system at postnatal age is one of the most challenging tasks in neuroscience and currently only a few effective methods are available. COMPARISON WITH EXISTING METHODS: For postnatal central nervous system cells, viral approaches are commonly used for genetic engineering but they face several biosafety requirements for production and use making them less accessible to the community. Conversely, lipid-based methods are widely used in cell culture but face limitation in vivo mainly due to the inflammatory responses they induce. To this aspect, the use of a transgenic mouse line can represent a credible answer to the community working on rat models still requires an effective and successful solution to circumvent these difficulties. NEW METHOD: We describe a new polymer-based gene delivery system allowing persistent and robust in vivo transfection with low DNA amount, reduced inflammation and high diffusion. The expression profile along the brain, the stability, the diffusion of the DNA together with the quantity of cells transfected were evaluated through in vivo approaches. RESULTS: With a single low-volume injection, we targeted different cell types within the rat brain. We measured the diffusion rate ranging from 1 to 5 mm based on the injected volume, in the three-dimensions axis. Finally, we modified brain susceptibility to epileptic seizures using a specific knock-down of the neuronal specific potassium-chloride transporter 2. CONCLUSIONS: This safe and easy system opens perspectives for non viral gene delivery in the rat brain with perspectives to study brain function in vivo.

Bugs for atopy: the Lactobacillus rhamnosus GG strategy for food allergy prevention and treatment in children.

Food allergy (FA) is a major health issue for children living in Western countries. At this time the only proven treatment for FA is elimination of offender antigen from the diet. It is becoming clear that the development of gut microbiota exerts a profound influence on immune system maturation and tolerance acquisition. Increasing evidence suggests that perturbations in gut microbiota composition of infants are implicated in the pathogenesis of FA. These findings have unveiled new strategies to prevent and treat FA using probiotics bacteria or bacterial substance to limit T-helper (Th)/Th2 bias, which changes during the disease course. Selected probiotics administered during infancy may have a role in the prevention and treatment of FA. Lactobacillus rhamnosus GG (LGG) is the most studied probiotic in this field. Administration of LGG in early life have a role in FA prevention. Preliminary evidence shows that LGG accelerates oral tolerance acquisition in cow's milk allergic infants. We are understanding the mechanisms elicited by LGG and metabolites in influencing food allergen sensitization. A deeper definition of these mechanisms is opening the way to new immunotherapeutics for children affected by FA that can efficiently limit the disease burden.

Skateboarding: more dangerous than roller skating or in-line skating.

OBJECTIVE: To describe the circumstances, severity, and outcomes of skating-related injuries among children admitted to trauma centers. DESIGN: A cross-sectional comparison of roller skaters (n = 154), in-line skaters (n = 190), and skateboarders (n = 254) aged 5 to 19 years who were hospitalized with injuries. SETTING: Seventy-nine hospitals and pediatric trauma centers participating in the National Pediatric Trauma Registry between October 1988 and April 1997. RESULTS: Three quarters (75.8%) of the study sample were male, nearly half (47.8%) were injured on roads, and more than one third (37.1%) had head injuries. Among skateboarders, 50.8% had head injuries compared with 33.7% of in-line skaters and 18.8% of roller skaters (P<.001). According to the Injury Severity Score, injuries to skateboarders were 8 times more likely to be severe or critical compared with roller skaters' injuries and more than 2 times as likely to be severe or critical compared with in-line skaters' injuries. Mean hospital length of stay was 6.0 days for skateboarders, 3.4 days for in-line skaters, and 2.4 days for roller skaters (P<.001). Skateboarders were more likely to be male and to be injured on roads than were in-line skaters or roller skaters. CONCLUSIONS: Skateboarding-related injuries are more severe and have more serious consequences than roller skating or in-line skating injuries. Research is needed to identify ergonomic and behavioral factors responsible for higher head injury risk to skateboarders, and interventions are needed to reduce the risk.

Horse-related injuries in pediatric patients.

PURPOSE: The aim of this study was to describe the characteristics, nature, severity and outcome of injuries from horse-related trauma in pediatric patients, aged of 19 years or younger. METHODS: Retrospective analysis was conducted of 315 patients recorded in the National Pediatric Trauma Registry from February 1995 to August 1999. RESULTS: A total of 62% of the 315 patients were girls. The median age of injury was 10 years. Sixty-five percent of the patients were injured while mounted on a horse, and the most common mechanism of injury was falling off the horse. The most frequent reason for hospital admission was skeletal fractures followed by head injuries. The head, neck, and face area was the most commonly injured anatomic site, followed by the upper extremity, the abdomen, and then the lower extremity. The median length of stay in the hospital was 2 days. Forty percent of the patients needed treatment in the intensive care unit with a median length of stay of 2 days. Thirty-nine percent of patients underwent surgical procedures. The Injury Severity Score ranged from moderate to critical in 31.5% of the children. There were 8 deaths, 2.5% of the injured children. The most common cause of mortality was head injuries. Of the 307 survivors, 3% were discharged to a rehabilitation center, and 2% of the children had 1 or more functional impairments lasting longer than 7 months after discharge. CONCLUSIONS: Horse-related trauma is frequent in children and can cause severe injuries resulting in death and long-term disability. Awareness of the nature of injuries is important to avoid underestimation of their severity.

Causes and outcomes of pediatric injuries occurring at school.

This study examines the causes and outcomes of injuries occurring at school and highlights the need for injury prevention strategies. Descriptive statistics were applied to data from a national pediatric trauma database on 1,558 K-12 graders injured at school severely enough to require hospitalization. Factors analyzed included age, gender, cause, place, time, injured body regions, use of hospital resources, in-hospital fatality rate, and functional limitations. Most injuries were unintentional (89.7%) and occurred mostly to children 10-14 years old. Almost half occurred in recreational areas. Falls and sports were the most frequent causes, but the pattern varied by grade and gender. Most children sustained injuries to the extremities (41.3%) or to the head (39.2%). Two percent sustained spinal cord injuries, mainly from sports. Eight children died, and 43.6% developed one or more functional limitations. Frequent, severe, and costly injuries should be the focus of school safety policies, and a mix of injury prevention strategies should be applied.

Outcomes of pediatric pedestrian injuries by locations of event.

Data from the National Pediatric Trauma Registry October 1995-October 2000, containing medical records of children under 20 years old hospitalized for pedestrian injuries, were examined. Demographics and outcome measures (nature and severity of injury, utilization of resources, deaths, and disability at discharge) were compared by location of occurrence. Pediatric pedestrian injuries resulted in severe outcomes whether the events occurred in driveways, public places, or in the road. Off the road injuries accounted for a significant proportion (13.2%) of all serious pedestrian injuries and disproportionately affected the youngest children. Prevention should consider the child's age and the location of injury occurrence.

Morbidity among pediatric motor vehicle crash victims: the effectiveness of seat belts.

It is well established that seat belts reduce mortality and morbidity among children. Data are presented for 413 children injured severely enough in motor vehicle crashes to require hospitalization. Of the unrestrained children, 4.5% died, compared with 2.4% of the belted children. Unrestrained children had a higher proportion of injuries in four of five anatomical regions, were more severely injured, stayed longer in the hospital, and were 15% more likely than belted children to be discharged with impairments.

Rehabilitation of severely injured children.

Injury is the leading cause of death and disability in childhood. Ideal systems of care integrate comprehensive management of acutely injured children with rehabilitation. We review the nature of childhood injury, its disabling consequences, and the best ways to manage the care of children with serious injuries.

Functional outcome in children with traumatic brain injury. Agreement between clinical judgment and the functional independence measure.

As improvements in the delivery of trauma care have increased survival from injury, it has become essential to assess the resulting morbidity to plan for medical and psychosocial services, particularly for children whose needs may be wide and long term. This paper focuses on the assessment of disability of 598 children, age 8 to 19 yr, hospitalized for traumatic brain injury with or without injury to other body regions, exclusive of spinal cord injury. The disability was measured at discharge from acute care in nine areas of functional activities and a recovery time assigned by a clinician. For the study, children were divided into three groups: those whose recovery was expected in less than 7 months (Group A: n = 463), in 7 to 24 months (Group B: n = 66) and in greater than 2 yr (Group C: n = 69). The clinician's expectation of recovery time significantly (P less than 0.01) reflected the injury severity as measured by the Glasgow Coma Scale and the Injury Severity Score. By the Glasgow Coma Scale, 16.4% were comatose on admission in Group A, 51.5% in Group B and 58% in Group C. The Injury Severity Score was significantly different with 25.5% severely injured in Group A, 68.2% in Group B and 84% in Group C. At discharge, 15% in Group A had four or more areas of impairments, 61% in Group B and 84% in Group C. The Functional Independence Measure confirmed the clinician's assessment of compromise with significantly (P less than 0.01) different average values of 110, 80 and 58 for Groups A, B and C, respectively.

An overview of the injury severity score and the new injury severity score.

OBJECTIVE: The research was undertaken to describe the injury severity score (ISS) and the new injury severity score (NISS) and to illustrate their statistical properties. DESIGN: Descriptive analysis and assessment of the distribution of these scales. METHODS: Three data sources--the National Pediatric Trauma Registry; the Massachusetts Uniform Hospital Discharge Data Set; and a trauma registry from an urban level I trauma center in Massachusetts--were used to describe the distribution of the ISS and NISS among injured patients. RESULTS: The ISS/NISS was found to have a positively skewed distribution and transformation did not improve their skewness. CONCLUSION: The findings suggest that for statistical or analytical purposes the ISS/ NISS should not be considered a continuous variable, particularly if ISS/NISS is treated as a continuous variable for correlation with an outcome measure.

Children with traumatic head injury: morbidity and postacute treatment.

The purpose of this paper was to describe pediatric head trauma and the factors that affect the extent, characteristics, and postacute service needs of functional limitations resulting from head trauma. Data are presented on 4,870 children who survived head injuries and who were enrolled in the National Pediatric Trauma Registry during 1985 to 1988. The sample excluded 349 children who died and 151 children who had impairments before injury. More than 50% of the surviving children sustained extracranial injury in addition to head injury, and this occurrence was related to age and mechanism of injury. Although 78% of the children were discharged from acute care without obvious impairments, 787 had one to three impairments, and 286 had four or more impairments. Discharge to rehabilitation or extended care facilities depended on the number and type of resulting impairments.