Hyaluronic Acid/Chitosan-g-Poly(ethylene glycol) Nanoparticles for Gene Therapy: An Application for pDNA and siRNA Delivery

Purpose  

To design hyaluronic acid (HA) and chitosan-g-poly(ethylene glycol) (CS-g-PEG) nanoparticles intended for a broad range of gene delivery applications.     

Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder

CONTEXT: Limbic structures are implicated in the genesis of attention-deficit/hyperactivity disorder (ADHD) by the presence of mood and cognitive disturbances in affected individuals and by elevated rates of mood disorders in family members of probands with ADHD. OBJECTIVE: To study the morphology of the hippocampus and amygdala in children with ADHD. DESIGN: A cross-sectional case-control study of the hippocampus and amygdala using anatomical magnetic resonance imaging. SETTINGS: University research institute. PATIENTS: One hundred fourteen individuals aged 6 to 18 years, 51 with combined-type ADHD and 63 healthy controls. MAIN OUTCOME MEASURES: Volumes and measures of surface morphology for the hippocampus and amygdala. RESULTS: The hippocampus was larger bilaterally in the ADHD group than in the control group (t = 3.35; P < .002). Detailed surface analyses of the hippocampus further localized these differences to an enlarged head of the hippocampus in the ADHD group. Although conventional measures did not detect significant differences in amygdalar volumes, surface analyses indicated the presence of reduced size bilaterally over the area of the basolateral complex. Correlations with prefrontal measures suggested abnormal connectivity between the amygdala and prefrontal cortex in the ADHD group. Enlarged subregions of the hippocampus tended to accompany fewer symptoms. CONCLUSIONS: The enlarged hippocampus in children and adolescents with ADHD may represent a compensatory response to the presence of disturbances in the perception of time, temporal processing (eg, delay aversion), and stimulus seeking associated with ADHD. Disrupted connections between the amygdala and orbitofrontal cortex may contribute to behavioral disinhibition. Our findings suggest involvement of the limbic system in the pathophysiology of ADHD.     

Cognitive impairment but preservation of sexual dimorphism in cognitive abilities in chronic schizophrenia

Neurocognitive impairment in schizophrenia is well established, though sex differences on cognitive tasks have produced equivocal findings. The present study was designed to examine performance of schizophrenia patients on a sexually dimorphic cognitive battery. The cognitive battery comprising tests of spatial (mental rotation, computerized version of the Benton Judgment of Line Orientation) and verbal abilities (phonological and semantic fluency) was administered to men (n = 22) and women (n = 21) with schizophrenia and healthy controls (n = 21 men and 21 women). A series of multivariate analyses showed that the patient group performed worse than controls on all the cognitive tasks. Cognitive sexual dimorphism on all spatial tasks favoring men and verbal tasks favoring women remained. Within the patient sample, correlational data demonstrated that earlier age at onset of illness related to poorer spatial performance. It is concluded that normal sexual dimorphism is undisturbed on both spatial and verbal tasks by the schizophrenia disease process.     

Sociocultural development and validation of lexicon for Asian-Indian individuals who use augmentative and alternative communication

Purpose. Individuals who temporarily or permanently are not able to communicate through use of gestures/signs, speech, and/or written communication mode benefit from the use of augmentative and alternative communication (AAC) systems. Effective communication skills for individuals who use an AAC system depend on appropriate lexicon. This study was designed to develop and validate a socially and culturally appropriate lexicon for Asian-Indians who use AAC.

Method. To this end, 120 individuals from India participated in this study. A composite list of lexical items was identified, using a structured social validation technique involving non-categorical and categorical nominations, and a rating of lexical items from a Picture Communication Symbols (PCS) lexicon.

Results. Data analysis indicated that 88 lexical items from the nomination task were not represented in the PCS lexicon and 247 items were rated as having no value for the Asian-Indian culture.

Conclusions. Findings suggest that while a lexicon from symbol sets developed for one culture might have considerable overlap across cultures, these lexicons may not be appropriate as a source of selecting a lexicon for an AAC user from a culturally and linguistically diverse background. Implications of these findings are discussed for speech-language pathologists and other rehabilitation professionals.     

The Tei index: a new prognostic index for patients with symptomatic heart failure.

BACKGROUND: The Tei index (TI) is a new echocardiographic/Doppler index of combined systolic and diastolic function, calculated as isovolumic relaxation time plus isovolumic contraction time divided by ejection time. This purpose of this study was to explore the prognostic value of TI in patients with heart failure from left ventricular (LV) systolic dysfunction. METHODS: Of 105 randomly selected participants with LV ejection fraction less than 30% and at least 1 hospitalization for heart failure, we included 60 patients in whom assessment of the TI was technically feasible. Using the patients' medical records, we collected information on several clinical and echocardiographic variables. We monitored patients for a mean duration of 24 +/- 19 months from the time of the echocardiogram. The study outcome was the composite of death from any cause or emergency heart transplant. RESULTS: The median value (interquartile range) of TI was 0.79 (0.54, 1.14). Of 57 patients (95%) with complete follow-up, 28 (49%) died, and 2 (3.5%) underwent emergency heart transplant at a mean duration of 17 +/- 14 months. Kaplan-Meier survival curves showed a higher cumulative incidence of the study end point among patients in the highest quartile of TI, compared with the other 3 quartiles (log rank P =.002). After adjustment for potential clinical confounders, TI in the highest quartile (TI > 1.14) was a significant independent predictor of the composite end point (odds ratio 5.3, 95% confidence interval 1.9 to 14.9, P =.0018). CONCLUSION: Prolonged TI (>1.14) is a powerful and independent predictor of poor clinical outcome in patients with symptomatic heart failure and severe LV systolic dysfunction.     

Liposomes as targeted drug delivery systems in the treatment of breast cancer

Solid tumors such as breast cancer have historically provided many challenges to anti-cancer therapy. Therapeutic hurdles to drug penetration in solid tumors include heterogeneous vascular supply and high interstitial pressures within tumor tissue, particularly in necrotic zones, lower pH and presence of leaky vasculature leading to reduced therapeutic response. Liposome based drug delivery systems offer the potential to enhance the therapeutic index of anti-cancer agents, either by increasing the drug concentration in tumor cells and/or by decreasing the exposure in normal tissues exploiting enhanced permeability and retention effect phenomenon and by utilizing targeting strategies. This review discusses recent trends in liposome-based drug delivery system both for diagnosis and treatment of breast cancer.     

Design and synthesis of positional isomers of 1-alkyl-2-trifluoromethyl-5 or 6-substituted benzimidazoles and their antimicrobial activity

A series of novel positional isomers of 1-alkyl-2-trifluoromethyl benzimidazole derivatives 3a–j and 4a–j have been synthesized and screened for antibacterial activity against gram positive bacteria viz, Bacillus subtilis, Staphylococcus aureus and gram negative bacteria viz., Escherichia coli, Pseudomonas aeruginosa and antifungal activity against Candida albicans, Aspergillus niger, Rhizopus oryzae and Saccharomyces cerevisiae. Results indicate that compounds 3b, 4b were having promising antibacterial and antifungal activity.