Preferential liver gene expression with polypropylenimine dendrimers.

Previously, the lower generation (DAB 8-generation 2 and DAB 16-generation 3) polypropylenimine dendrimers have been shown to be effective gene delivery systems in vitro. In the current work, we sought to: (a) test the effect of the strength of the carrier, DNA electrostatic interaction on gene transfer and (b) to study the in vivo gene transfer activity of these low molecular weight (<1687 Da) non-amphiphilic plain and quaternary ammonium gene carriers. Towards this aim, methyl quaternary ammonium derivatives of DAB 4 (generation 1), DAB 8, DAB 16 and DAB 32 (generation 4) were synthesised to give Q4, Q8, Q16 and Q32, respectively. Quaternisation of DAB 8 proved to be critical in improving DNA binding, as evidenced by data from the ethidium bromide exclusion assay and dendrimer-DNA colloidal stability data. This improved colloidal stability had a major effect on vector tolerability, as Q8-DNA formulations were well tolerated on intravenous injection while a similar DAB 8-DNA dose was lethally toxic by the same route. Quaternisation also improved the in vitro cell biocompatibility of DAB 16-DNA and DAB 32-DNA dendrimer complexes by about 4-fold but not that of the lower generation DAB 4-DNA and DAB 8-DNA formulations. In contrast to previous reports with non-viral gene delivery systems, the intravenous administration of DAB 16-DNA and Q8-DNA formulations resulted in liver targeted gene expression as opposed to the lung targeted gene expression obtained with the control polymer-Exgen 500 [linear poly(ethylenimine)] and a lung avoidance hypothesis is postulated. We conclude that the polypropylenimine dendrimers are promising gene delivery systems which may be used to target the liver and avoid the lung and also that molecular modifications conferring colloidal stability on gene delivery formulations have a profound effect on their tolerability on intravenous administration.     

Profiles of Neurological Outcome Prediction Among Intensivists

Background  

Advances in intensive care medicine have increased survival rates of patients with critical neurological conditions. The focus of prognostication for such patients is therefore shifting from predicting chances of survival to meaningful neurological recovery. This study assessed the variability in long-term outcome predictions among physicians and aimed to identify factors that may account for this variability.     

Age determines memory for face identity and expression

Background: The recognition of facial expressions is an important component of emotion processing which contributes to interactional behavior. One of the factors highly associated with potential decline of ability in behavioral tasks is age. Methods: We have investigated age‐related changes in facial identity and expression memory of healthy subjects in three age groups: young adults (20–40 years), elderly adults (60–80 years) and, for the first time in the literature, very old adults (over 80 years of age). Using a picture test, photographs of faces with happy or angry expressions were presented to study participants during the encoding task, and the memory for identity and emotional facial expression was investigated in a subsequent recognition task showing emotionally neutral faces. Half of the faces presented in the recognition task were initially shown in the encoding task. Results: Age interacted with the memory process: the ability to recognize both facial identity and emotional expression declined with advanced age. Happy facial expressions were better recognized in all age groups. Although there was a continuous overall decrease in recognition of both happy and angry expressions with advanced age, the effect favoring happy facial expressions was stable also in very old adults. Other factors such as gender or educational level did not affect the memory process for facial expressions. Conclusions: Our findings suggest that age is a significant determinant of memory for facial identity and emotional expression, and that, similar to younger adults, the recognition process of the elderly favors happy emotional facial expressions.     

Immunohistological identification of cell subsets in human gingival after local treatment for gingivitis or periodontitis

The cellular infiltrate present in human diseased gingiva was analyzed in biopsies from 12 patients with gingivitis or periodontitis. The samples studied had been obtained in the course of surgery at inflammatory sites remaining after institution of periodontal treatment. Histological and immunological techniques were used to identify macrophages, B-cells, plasma-cells, T-cells and T cell subsets, as well as cells expressing class II HLA membrane antigens. T-cells appeared as the predominant population, but plasma-cells were also visualized in nearly all samples. Both OKT4+ and OKT8+ cells were seen in all cases, the latter being more numerous in periodontitis patients. Interdigitating-like cells were observed, positively labelled for class II antigens, as well as macrophages which were more numerous in periodontitis patients. These results suggest the participation of all components of the immune response in gingival disease, in a way resembling chronic recurrent inflammatory diseases.     

Mother's understanding of allergen induced asthma

Forty-nine children with asthma and their mothers were interviewed regarding their knowledge of asthma, factors that precipitated attacks, and how they attempted to reduce the probability of an attack. Many mothers and children were well aware of factors that precipitated attacks, but took little positive action to reduce attacks. The data suggest that much ill-health in asthmatic children could be reduced by improving education available to mothers and children.     

The influence of in-season injury prevention training on lower-extremity kinematics during landing in female soccer players.

OBJECTIVE: To examine the influence of in-season injury prevention training on hip and knee kinematics during a landing task. DESIGN: Longitudinal pre-post intervention study. SETTING: Testing sessions were conducted in a biomechanics research laboratory. PARTICIPANTS: Eighteen female soccer players between the ages of 14 and 17 participated in this study. All subjects were healthy with no current complaints of lower extremity injury. INTERVENTIONS: Testing sessions were conducted prior to and following a season of soccer practice combined with injury prevention training. MAIN OUTCOME MEASUREMENTS: During each testing session three-dimensional kinematics were collected while each subject performed a drop landing task. Peak hip and knee joint angles were measured during the early deceleration phase of landing and compared between pre- and post-training using paired t-tests. RESULTS: Following a season of soccer practice combined with injury prevention training, females demonstrated significantly less hip internal rotation (7.1 degrees vs. 1.9 degrees; P = 0.01) and significantly greater hip abduction (-4.9 degrees vs. -7.7 degrees; P = 0.02). No differences in knee valgus or knee flexion angles were found post-season. CONCLUSIONS: Female soccer players exhibited significant changes in hip kinematics during a landing task following in-season injury prevention training. Our results support the premise that a season of soccer practice combined with injury prevention training is effective in altering lower extremity motions that may play a role in predisposing females to ACL injury.