Site directed vascular gene delivery in vivo by ultrasonic destruction of magnetic nanoparticle coated microbubbles

Site specific vascular gene delivery for therapeutic implications is favorable because of reduction of possible side effects. Yet this technology faces numerous hurdles that result in low transfection rates because of suboptimal delivery. Combining ultrasonic microbubble technology with magnetic nanoparticle enhanced gene transfer could make it possible to use the systemic vasculature as the route of application and to magnetically trap these compounds at the target of interest. In this study we show that magnetic nanoparticle-coated microbubbles bind plasmid DNA and successfully deliver it to endothelial cells in vitro and more importantly transport their cargo through the vascular system and specifically deliver it to the vascular wall in vivo at sites where microbubbles are retained by magnetic force and burst by local ultrasound application. This resulted in a significant enhancement in site specific gene delivery compared with the conventional microbubble technique. Thus, this technology may have promising therapeutic potential.From the Clinical EditorThis work focuses on combining ultrasonic microbubble technology with magnetic nanoparticle enhanced gene transfer to enable targeted gene delivery via the systemic vasculature and magnetic trapping of these compounds at the target of interest.     

Post-traumatic headache after mild traumatic brain injury in a one-year follow up study – risk factors and return to work

BackgroundPost-traumatic headache (PTH) is a common symptom following mild traumatic brain injury (mTBI). Patients at risk to develop acute PTH (aPTH) and further persistent PTH (pPTH) need to be recognized.MethodsThis is a one-year follow-up of 127 patients with mTBI, aged 18 to 68, referred to outpatient clinic in the Helsinki University Hospital. Symptoms were assessed at the emergency department (ED), with structured interview at outpatient clinic visit and with Rivermead post-concussion symptom questionnaire at one, three, and 12 months after injury. Psychiatric disorders were assessed with Structured Clinical Interview for DSM-IV Axis I disorders at 3-4 months and return to work (RTW) from patient records.ResultsAt one month, 77/127 patients (61%) had aPTH. According to multiple logistic regression analysis, risk factors for aPTH were headache at the emergency department (ED) (OR 5.43), other pain (OR 3.19), insomnia (OR 3.23), and vertigo (OR 5.98). At three months, 17 patients (22% of aPTH patients) had developed pPTH, and at one year, 4 patients (24% of pPTH patients) still presented with pPTH. Risk factors for pPTH at three months were older age (OR 1.06) and current insomnia (OR 12.3). The frequency of psychiatric disorders did not differ between the groups. pPTH patients performed worse on their RTW.ConclusionsRisk factors for aPTH were insomnia, headache at ED, other pain, and vertigo and for pPTH, insomnia and older age. RTW rate was lower among pPTH patients.     

Upward weight percentile crossing in infancy and early childhood independently predicts fat mass in young adults: the Stockholm Weight Development Study (SWEDES)

BACKGROUND: Rapid early postnatal weight gain predicts increased subsequent obesity and related disease risks. However, the exact timing of adverse rapid postnatal weight gain is unclear. OBJECTIVE: The objective was to examine the associations between rapid weight gain in infancy and in early childhood in relation to body composition at age 17 y. DESIGN: This prospective cohort study was conducted in 248 (103 males) singletons and their mothers. Height and weight were measured at birth, 6 mo, and 3 and 6 y. The rates of weight gain during infancy (0-6 mo) and early childhood (3-6 y) were calculated as changes in sex- and age-adjusted weight SD scores during these time periods. At 17 y, body composition was measured by air-displacement plethysmography. RESULTS: Increasing weight gain during infancy and early childhood were both independently associated with larger body mass index, fat mass, relative fat mass, fat-free mass, and waist circumference at 17 y (P < 0.005 for all; adjusted for sex, birth weight, gestational age, current height, maternal socioeconomic status, and maternal fat mass). Rapid weight gain in infancy, but not in early childhood, also predicted taller height at 17 y (P < 0.001). CONCLUSIONS: Rapid weight gain in both infancy and early childhood is a risk factor for adult adiposity and obesity. Rapid weight gain in infancy also predicted taller adult height. We hypothesize that rapid weight gains in infancy and early childhood are different processes and may allow separate opportunities for early intervention against obesity risk later in life.     

Association of weight gain in infancy and early childhood with metabolic risk in young adults

CONTEXT: Early postnatal life has been suggested as an important window during which risks for long-term health may be influenced. OBJECTIVE: The aim of this study was to examine the independent associations between weight gain during infancy (0-6 months) and early childhood (3-6 yr) with components of the metabolic syndrome in young adults. DESIGN: This was a prospective cohort study (The Stockholm Weight Development Study). SETTING: The study was conducted in a general community. PARTICIPANTS: Subjects included 128 (54 males) singletons, followed from birth to 17 yr. MAIN OUTCOME MEASURE: None of these young adults met the full criteria for the metabolic syndrome. We therefore calculated a continuous clustered metabolic risk score by averaging the standardized values of the following components: waist circumference, blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, glucose, and insulin level. RESULTS: Clustered metabolic risk at age 17 yr was predicted by weight gain during infancy (standardized beta = 0.16; P < 0.0001) but not during early childhood (standardized beta = 0.10; P = 0.23), adjusted for birth weight, gestational age, current height, maternal fat mass, and socioeconomic status at age 17 yr. Further adjustment for current fat mass and weight gain during childhood did not alter the significant association between infancy weight gain with the metabolic risk score (standardized beta = 0.20; P = 0.007). CONCLUSIONS: Rapid weight gain during infancy (0-6 months) but not during early childhood (3-6 yr) predicted clustered metabolic risk at age 17 yr. Early interventions to moderate rapid weight gain even at very young ages may help to reduce adult cardiovascular disease risks.     

Associations between physical activity and fat mass in adolescents: the Stockholm Weight Development Study

BACKGROUND: Obesity is multifactorial. However, the accumulation of fat mass (FM) is proposed to be due to a positive energy balance, which may be caused by reduced physical activity (PA). OBJECTIVE: The objectives of the study were to describe the independent associations between PA and FM in adolescents and to describe the intergenerational association of FM between mothers and their offspring. DESIGN: We conducted a cross-sectional study in 445 (190 M, 255 F) 17-y-old adolescents and their mothers. PA was assessed with a self-reported questionnaire and validated by comparison with accelerometric data in a subsample of the cohort. Body composition was measured by using air-displacement plethysmography. RESULTS: Males were significantly more active than were females (P<0.01). PA was significantly and inversely associated with FM (beta=-3.63, P=0.005) and percentage FM (beta=-3.117, P=0.017) in males but not in females (beta=-0.576, P=0.54; beta=-0.532, P=0.59, respectively) after adjustment for birth weight and maternal FM and education level. However, FM and percentage FM in females were significantly associated with maternal FM (beta=0.159, P<0.0001; beta=0.145, P=0.002, respectively) and education level (beta=-1.048, P<0.005; beta=-1.085, P=0.006, respectively). No such associations were observed in males. CONCLUSIONS: PA was independently associated with FM in males but not in females. The data also showed an intergenerational association of FM between mothers and their daughters but not between mothers and their sons.