Dose-dependent delivery of genes to the cerebral cortex via the nasal route.

The use of nucleic acids to treat various brain diseases could offer new therapeutic modalities, providing the nucleic acids may be effectively delivered to areas of the brain using non-toxic vectors. In this study, we present evidence that genes may be successfully delivered in a dose-dependent manner via the nose, primarily to the cerebral cortex using a 6-O-glycolchitosan (GC) formulation of plasmid DNA. Positively charged (zeta potential = +13 - + 25 mV) GC-DNA nanoparticles of 100-500 nm in diameter with favourable cell biocompatibility were shown to deliver the reporter Green Fluorescent Protein (GFP) plasmid to the U87MG cell line and the resulting protein expression was not significantly different from that obtained with Lipofectamine 2000.

Gene Targeting to the Cerebral Cortex Following Intranasal Administration of Polyplexes.

Gene delivery to the cerebral cortex is challenging due to the blood brain barrier and the labile and macromolecular nature of DNA. Here we report gene delivery to the cortex using a glycol chitosan-DNA polyplex (GCP). In vitro, GCPs carrying a reporter plasmid DNA showed approximately 60% of the transfection efficiency shown by Lipofectamine lipoplexes (LX) in the U87 glioma cell line.

The Route to Autism Spectrum Diagnosis in Pediatric Practice in Bulgaria.

Unlabelled: Diagnosis of autism spectrum disorder (ASD) before the age of three years is a challenge. Analyzing the present practice may help reaching that goal.

Aim: To investigate developmental abnormalities and diagnostic pathway of ASD patients in pediatric practice.

Hyaluronidase Coated Molecular Envelope Technology Nanoparticles Enhance Drug Absorption via the Subcutaneous Route.

Parenteral chemotherapy is usually administered intravenously, although patient preference and health economics suggest the subcutaneous (sc) route could be an attractive alternative. However, due to the low aqueous solubility of hydrophobic drugs and injection volume limitations, the total amount of drug that can be administered in a single sc injection is frequently insufficient. We have developed hyaluronidase coated nanoparticles (NPs) that efficiently encapsulate such drugs, thus addressing both issues and allowing sufficient amounts of hydrophobic drug to be administered and absorbed effectively.

An Individualized Approach to Neuroplasticity After Early Unilateral Brain Damage.

Reorganization after early lesions in the developing brain has been an object of extensive scientific work, but even growing data from translational neuroscience studies in the last 20 years does not provide unified factors for prediction of type of reorganization and rehabilitation potential of patients with unilateral cerebral palsy (UCP) due to pre/perinatal insult. To analyze the type of motor, language, and sensory brain reorganization in patients with right-sided cerebral palsy due to pre/perinatal isolated left-sided brain lesions taking into consideration the type (cortico-subcortical or periventricular) and extent (gray and white matter damage) of the lesion, etiology, comorbidity, and other postnatal factors that could have played a role in the complex process of brain plasticity. Eight patients with unilateral right cerebral palsy were included in the study.

Epilepsy in Children with Autistic Spectrum Disorder.

The comorbidity of autistic spectrum disorder (ASD) and epilepsy has been widely discussed but many questions still remain unanswered. The aim of this study was to establish the occurrence of epilepsy among children with ASD to define the type of epileptic seizures and syndromes, the age of onset of epilepsy, EEG abnormalities, the used antiepileptic drugs and the therapeutic responses for seizures and autistic behavior, as well as to find some correlations between epilepsy and gender, etiology and intellectual disability (ID). A retrospective study of medical files of 59 patients (aged 1⁻18 years) with ASD during a 5-year period was performed.

An Optical Assay for Synaptic Vesicle Recycling in Cultured Neurons Overexpressing Presynaptic Proteins.

At active presynaptic nerve terminals, synaptic vesicles undergo cycles of exo- and endocytosis. During recycling, the luminal domains of SV transmembrane proteins become exposed at the cell surface. One of these proteins is Synaptotagmin-1 (Syt1).

[Complex technology for water and wastewater disinfection and its industrial realization in prototype unit].

Usage of complex automated electrolysis unit for drinking water disinfection and wastewater oxidation and coagulation is scoped, its ecological and energy efficiency is shown. Properties of technological process of anolyte production using membrane electrolysis of brine for water disinfection in municipal pipelines and potassium ferrate production using electrochemical dissolution of iron anode in NaOH solution for usage in purification plants are listed. Construction of modules of industrial prototype for anolyte and ferrate production and applied aspects of automation of complex electrolysis unit are proved.

Spontaneous Spondylodiscitis - Epidemiology, Clinical Features, Diagnosis and Treatment.

Spontaneous spondylodiscitis is a rare but serious infectious disease which is a combination of an inflammatory process, involving one or more adjacent vertebral bodies (spondylitis), the intervertebral discs (discitis) and finally - the neighboring neural structures. In most cases the condition is due to a hematogenous infection and can affect all regions of the spinal cord, but it is usually localized in the lumbar area. The most common clinical symptom is a pronounced, constant and increasing nocturnal paravertebral pain, while consequently different degrees of residual neurological symptoms from nerve roots and/or spinal cord may appear.

Preschool Fantasy-Reality Discrimination: Influences of Trait and Primed Fearfulness.

Distinguishing between fantasy and reality is an important developmental milestone, achieved in the preschool years, that has been linked to children's cognitive capabilities and emotional knowledge. The authors examined the influence of both trait and prime fearfulness on preschoolers' ability to differentiate between fantastic and real situations. Forty 3-5-year-old preschoolers were administered a fearfulness assessment, a standard theory-of-mind task, and a fantasy-reality discrimination task (with or without a fear prime).

Use of Peptide Libraries for Identification and Optimization of Novel Antimicrobial Peptides.

The increasing rates of resistance among bacteria and to a lesser extent fungi have resulted in an urgent need to find new molecules that hold therapeutic promise against multidrug-resistant strains. Antimicrobial peptides have proven very effective against a variety of multidrug-resistant bacteria. Additionally, the low levels of resistance reported towards these molecules are an attractive feature for antimicrobial drug development.

Cellular origins of cold-induced brown adipocytes in adult mice.

This work investigated how cold stress induces the appearance of brown adipocytes (BAs) in brown and white adipose tissues (WATs) of adult mice. In interscapular brown adipose tissue (iBAT), cold exposure increased proliferation of endothelial cells and interstitial cells expressing platelet-derived growth factor receptor, α polypeptide (PDGFRα) by 3- to 4-fold. Surprisingly, brown adipogenesis and angiogenesis were largely restricted to the dorsal edge of iBAT.

A single dose of whole inactivated H7N9 influenza vaccine confers protection from severe disease but not infection in ferrets.

The H7N9 influenza virus caused significant mortality and morbidity in infected humans during an outbreak in China in 2013 stimulating vaccine development efforts. As previous H7-based vaccines have been poorly immunogenic in humans we sought to determine the immunogenic and protective properties of an inactivated whole virus vaccine derived from a 2013 H7N9 virus in ferrets. As whole virus vaccine preparations have been shown to be more immunogenic in humans, but less likely to be used, than split or surface antigen formulations, we vaccinated ferrets with a single dose of 15, 30, or 50 μg of the vaccine and subsequently challenged with wild-type A/Anhui/1/2013 (H7N9) either by direct instillation or by contact with infected animals.

Cationic antimicrobial peptides as potential new therapeutic agents in neonates and children: a review.

Purpose Of Review: Antimicrobial resistance towards conventional antibiotics is a serious problem for modern medicine and for our society. Multidrug-resistant bacteria are very difficult to treat and treatment options have begun to run out. Here, we summarize the newest studies of drug development using cationic antimicrobial peptides as lead molecules for novel antimicrobial drugs.

Identification of an adipogenic niche for adipose tissue remodeling and restoration.

The regulatory events guiding progenitor activation and differentiation in adult white adipose tissue are largely unknown. We report that induction of brown adipogenesis by β3-adrenergic receptor (ADRB3) activation involves the death of white adipocytes and their removal by M2-polarized macrophages. Recruited macrophages express high levels of osteopontin (OPN), which attracts a subpopulation of PDGFRα+ progenitors expressing CD44, a receptor for OPN.

In vivo identification of bipotential adipocyte progenitors recruited by β3-adrenoceptor activation and high-fat feeding.

Nutritional and pharmacological stimuli can dramatically alter the cellular phenotypes in white adipose tissue (WAT). Utilizing genetic lineage tracing techniques, we demonstrate that brown adipocytes (BA) that are induced by β3-adrenergic receptor activation in abdominal WAT arise from the proliferation and differentiation of cells expressing platelet-derived growth factor receptor alpha (PDGFRα), CD34, and Sca-1 (PDGFRα(+) cells). PDGFRα(+) cells have a unique morphology in which extended processes contact multiple cells in the tissue microenvironment.

Avian influenza viruses isolated from mallards in Bulgaria.

Bulgaria has a unique geographic position in Europe, with two migratory wild bird routes, Via Pontica and Via Aristotelis, passing through the country. Via Pontica is the second-largest migration route in Europe, with hundreds of thousands of birds, representing more than 110 species, wintering in lakes by the Black Sea and the wetlands near the Danube River. Via Aristotelis is situated in West Bulgaria along the Strouma and Mesta river valleys, and it is of regional importance for the Balkan Peninsula.

An Achilles' heel in an amyloidogenic protein and its repair: insulin fibrillation and therapeutic design.

Insulin fibrillation provides a model for a broad class of amyloidogenic diseases. Conformational distortion of the native monomer leads to aggregation-coupled misfolding. Whereas beta-cells are protected from proteotoxicity by hexamer assembly, fibrillation limits the storage and use of insulin at elevated temperatures.

Expression of heparin-binding EGF-like growth factor in term chorionic villous explants and its role in trophoblast survival.

Heparin-binding EGF-like growth factor (HBEGF) induces trophoblast extravillous differentiation and prevents apoptosis. These functions are compromised in preeclampsia. Because HBEGF is downregulated in placentas delivered by women with preeclampsia, we have examined its expression and cytoprotective activity in term villous explants.

Diminished survival of human cytotrophoblast cells exposed to hypoxia/reoxygenation injury and associated reduction of heparin-binding epidermal growth factor-like growth factor.

Objective: The antiapoptotic action of heparin-binding epidermal growth factor (HBEGF)-like growth factor and its regulation by O(2) constitutes a key factor for trophoblast survival. The hypothesis that cytotrophoblast survival is compromised by exposure to hypoxia-reoxygenation (H/R) injury, which may contribute to preeclampsia and some missed abortions, prompted us to investigate HBEGF regulation and its role as a survival factor during H/R in cytotrophoblast cells.

Study Design: A transformed human first-trimester cytotrophoblast cell line HTR-8/SVneo was exposed to H/R (2% O(2) followed by 20% O(2)) and assessed for HBEGF expression and cell death.

Polymorphic fibril formation by residues 10-40 of the Alzheimer's beta-amyloid peptide.

We report investigations of the morphology and molecular structure of amyloid fibrils comprised of residues 10-40 of the Alzheimer's beta-amyloid peptide (Abeta(10-40)), prepared under various solution conditions and degrees of agitation. Omission of residues 1-9 from the full-length Alzheimer's beta-amyloid peptide (Abeta(1-40)) did not prevent the peptide from forming amyloid fibrils or eliminate fibril polymorphism. These results are consistent with residues 1-9 being disordered in Abeta(1-40) fibrils, and show that fibril polymorphism is not a consequence of disorder in residues 1-9.

The effect of dystocia and previous cesarean uterine scar on the tensile properties of the lower uterine segment.

Objective: The remodeling of uterine connective tissue during labor can lead to the reorganization of the extracellular matrix that, in turn, may influence the biomechanical properties of the myometrial wall. We hypothesized that the stretching of the lower uterine segment in laboring women with dystocia changes the viscoelastic properties of the uterine wall.

Study Design: We tested the tensile strength of lower uterine segment myometrium in 68 pregnant women at term.

Human trophoblast survival at low oxygen concentrations requires metalloproteinase-mediated shedding of heparin-binding EGF-like growth factor.

Heparin-binding EGF-like growth factor (HBEGF), which is expressed in the placenta during normal pregnancy, is down regulated in pre-eclampsia, a human pregnancy disorder associated with poor trophoblast differentiation and survival. This growth factor protects against apoptosis during stress, suggesting a role in trophoblast survival in the relatively low O(2) ( approximately 2%) environment of the first trimester conceptus. Using a well-characterized human first trimester cytotrophoblast cell line, we found that a 4-hour exposure to 2% O(2) upregulates HBEGF synthesis and secretion independently of an increase in its mRNA.

Experimental constraints on quaternary structure in Alzheimer's beta-amyloid fibrils.

We describe solid-state nuclear magnetic resonance (NMR) measurements on fibrils formed by the 40-residue beta-amyloid peptide associated with Alzheimer's disease (Abeta(1-40)) that place constraints on the identity and symmetry of contacts between in-register, parallel beta-sheets in the fibrils. We refer to these contacts as internal and external quaternary contacts, depending on whether they are within a single molecular layer or between molecular layers. The data include (1) two-dimensional 13C-13C NMR spectra that indicate internal quaternary contacts between side chains of L17 and F19 and side chains of I32, L34, and V36, as well as external quaternary contacts between side chains of I31 and G37; (2) two-dimensional 15N-13C NMR spectra that indicate external quaternary contacts between the side chain of M35 and the peptide backbone at G33; (3) measurements of magnetic dipole-dipole couplings between the side chain carboxylate group of D23 and the side chain amine group of K28 that indicate salt bridge interactions.