Obesity is associated with decreased μ-opioid but unaltered dopamine D2 receptor availability in the brain.

Neurochemical pathways involved in pathological overeating and obesity are poorly understood. Although previous studies have shown increased μ-opioid receptor (MOR) and decreased dopamine D2 receptor (D2R) availability in addictive disorders, the role that these systems play in human obesity still remains unclear. We studied 13 morbidly obese women [mean body mass index (BMI), 42 kg/m(2)] and 14 nonobese age-matched women, and measured brain MOR and D2R availability using PET with selective radioligands [(11)C]carfentanil and [(11)C]raclopride, respectively.

Phase and amplitude correlations in resting-state activity in human stereotactical EEG recordings.

Inter-areal interactions of neuronal oscillations may be a key mechanism in the coordination of anatomically distributed neuronal processing. In humans, invasive stereo-electroencephalography (SEEG) is emerging as a reference method for electrophysiological recordings because of its excellent spatial and temporal resolution. It could thus be also considered an optimal method for mapping neuronal inter-areal interactions.

Multifunctional porous silicon nanoparticles for cancer theranostics.

Nanomaterials provide a unique platform for the development of theranostic systems that combine diagnostic imaging modalities with a therapeutic payload in a single probe. In this work, dual-labeled iRGD-modified multifunctional porous silicon nanoparticles (PSi NPs) were prepared from dibenzocyclooctyl (DBCO) modified PSi NPs by strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry. Hydrophobic antiangiogenic drug, sorafenib, was loaded into the modified PSi NPs to enhance the drug dissolution rate and improve cancer therapy.

Neural circuits for cognitive appetite control in healthy and obese individuals: an fMRI study.

The mere sight of foods may activate the brain's reward circuitry, and humans often experience difficulties in inhibiting urges to eat upon encountering visual food signals. Imbalance between the reward circuit and those supporting inhibitory control may underlie obesity, yet brain circuits supporting volitional control of appetite and their possible dysfunction that can lead to obesity remain poorly specified. Here we delineated the brain basis of volitional appetite control in healthy and obese individuals with functional magnetic resonance imaging (fMRI).

Dual-drug delivery by porous silicon nanoparticles for improved cellular uptake, sustained release, and combination therapy.

Dual-drug delivery of antiangiogenic and chemotherapeutic drugs can enhance the therapeutic effect for cancer therapy. Conjugation of methotrexate (MTX) to porous silicon (PSi) nanoparticles (MTX-PSi) with positively charged surface can improve the cellular uptake of MTX and inhibit the proliferation of cancer cells. Herein, MTX-PSi conjugates sustained the release of MTX up to 96 h, and the released fragments including MTX were confirmed by mass spectrometry.

Comparison of BD Max Cdiff and GenomEra C. difficile molecular assays for detection of toxigenic Clostridium difficile from stools in conventional sample containers and in FecalSwabs.

In this study, the usability and performance of GenomEra™ C. difficile and BD Max™ Cdiff nucleic acid amplification tests (NAATs) for the detection of toxigenic Clostridium difficile were investigated in comparison with toxigenic culture and C. difficile toxin A- and toxin B-detecting immunochromatographic antigen (IA) test, the Tox A/B QuikChek®.

Functionalization of alkyne-terminated thermally hydrocarbonized porous silicon nanoparticles with targeting peptides and antifouling polymers: effect on the human plasma protein adsorption.

Porous silicon (PSi) nanomaterials combine a high drug loading capacity and tunable surface chemistry with various surface modifications to meet the requirements for biomedical applications. In this work, alkyne-terminated thermally hydrocarbonized porous silicon (THCPSi) nanoparticles were fabricated and postmodified using five bioactive molecules (targeting peptides and antifouling polymers) via a single-step click chemistry to modulate the bioactivity of the THCPSi nanoparticles, such as enhancing the cellular uptake and reducing the plasma protein association. The size of the nanoparticles after modification was increased from 176 to 180-220 nm.

Inhibitory activity of the isoflavone biochanin A on intracellular bacteria of genus Chlamydia and initial development of a buccal formulation.

Given the established role of Chlamydia spp. as causative agents of both acute and chronic diseases, search for new antimicrobial agents against these intracellular bacteria is required to promote human health. Isoflavones are naturally occurring phytoestrogens, antioxidants and efflux pump inhibitors, but their therapeutic use is limited by poor water-solubility and intense first-pass metabolism.

Safety and toxicity concerns of orally delivered nanoparticles as drug carriers.

Introduction: The popularity of nanotechnology is increasing and revolutionizing extensively the drug delivery field. Nanoparticles, as carriers for oral delivery of drugs, have been claimed as the perfect candidates to overcome the poor bioavailability of most of the drugs by improving their solubility and/or permeability across biological barriers. However, this is still a promise to be fulfilled.

Microfluidic assisted one-step fabrication of porous silicon@acetalated dextran nanocomposites for precisely controlled combination chemotherapy.

An advanced nanocomposite consisting of an encapsulated porous silicon (PSi) nanoparticle and an acid-degradable acetalated dextran (AcDX) matrix (nano-in-nano), was efficiently fabricated by a one-step microfluidic self-assembly approach. The obtained nano-in-nano PSi@AcDX composites showed improved surface smoothness, homogeneous size distribution, and considerably enhanced cytocompatibility. Furthermore, multiple drugs with different physicochemical properties have been simultaneously loaded into the nanocomposites with a ratiometric control.

The use of molecular methods for the detection and identification of methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen in many hospitals and long-term care facilities as well as in the community. To limit the spread of MRSA, early detection and proper treatment are essential. Because conventional culture as gold standard is time consuming, new techniques such as PCR-based and hybridization assays have emerged for the rapid detection of MRSA.

In vitro assessment of biopolymer-modified porous silicon microparticles for wound healing applications.

The wound healing stands as very complex and dynamic process, aiming the re-establishment of the damaged tissue's integrity and functionality. Thus, there is an emerging need for developing biopolymer-based composites capable of actively promoting cellular proliferation and reconstituting the extracellular matrix. The aims of the present work were to prepare and characterize biopolymer-functionalized porous silicon (PSi) microparticles, resulting in the development of drug delivery microsystems for future applications in wound healing.

Antihyperglycemic potential of incretins orally delivered via nano and microsystems and subsequent glucoregulatory effects.

Type 2 diabetes mellitus (T2DM) is mainly associated with impaired insulin secretion by the pancreatic β-cells, insulin resistance and elevated hepatic gluconeogenesis. Incretin based treatments for T2DM are now widely investigated and used. The incretin based therapies mainly include incretin hormones which are glucose-dependent insulinotropic peptides (GIP) and glucagon like peptide-1 (GLP-1) released from the endocrinal cells in the small intestine in response to food intake.

Controlled transdermal delivery of leuprorelin by pulsed iontophoresis and ion-exchange fiber.

Poor transport efficacy and issues related to biological variation are major concerns in the development of novel iontophoretic devices for the transdermal delivery of therapeutic peptides. The objective of this study was to examine the impact of constant and pulsed current on the transport of nonapeptide leuprorelin acetate across porcine epidermis. Also, the potential of drug delivery system combining iontophoresis and ion-exchange fibers as drug matrices for the delivery of the same peptide was tested.

Advanced Nanomedicines for the Treatment and Diagnosis of Myocardial Infarction and Heart Failure.

Nanotechnology has impacted tremendously the medical research with increasing importance in the development of new therapeutic approaches and applications. Among these applications, the use of nanocarriers has gained particular interest in order to achieve successful delivery of therapeutics and imaging agents for the treatment and diagnostics of different diseases, such as cancer, infections, diabetes, lung, brain and cardiovascular diseases. Heart failure (HF) is a complex clinical syndrome derived from multiple causes that arise from secondary to inherited or acquired abnormalities of cardiac structure and/or function.

Interaction studies between indomethacin nanocrystals and PEO/PPO copolymer stabilizers.

Purpose: The lack of effective screening methods and systemic understanding of interaction mechanisms complicates the stabilizer selection process for nanocrystallization. This study focuses on the efficiency of stabilizers with various molecular compositions and structures to stabilize drug nanocrystals.

Methods: Five structurally different polymers were chosen as stabilizers for indomethacin nanocrystals.

Surface chemistry dependent immunostimulative potential of porous silicon nanoplatforms.

Nanoparticles (NPs) have been suggested for immunotherapy applications in order to optimize the delivery of immuno-stimulative or -suppressive molecules. However, low attention towards the impact of the NPs' physicochemical properties has presented a major hurdle for developing efficient immunotherapeutic agents. Here, the effects of porous silicon (PSi) NPs with different surface chemistries were evaluated on human monocyte-derived dendritic cells (MDDCs) and lymphocytes in order to highlight the importance of the NPs selection in immuno-stimulative or -suppressive treatment.

The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium.

Glucagon like peptide-1 (GLP-1) is an incretin hormone that is in the pipeline for type 2 diabetes mellitus (T2DM) therapy. However, oral administration of GLP-1 is hindered by the harsh conditions of the gastrointestinal tract and poor bioavailability. In this study, three nanosystems composed by three different biomaterials (poly(lactide-co-glycolide) polymer (PLGA), Witepsol E85 lipid (solid lipid nanoparticles, SLN) and porous silicon (PSi) were developed and loaded with GLP-1 to study their permeability in vitro.

Amine-modified hyaluronic acid-functionalized porous silicon nanoparticles for targeting breast cancer tumors.

Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA(+)) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi-HA(+) nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization.

In vivo biocompatibility of porous silicon biomaterials for drug delivery to the heart.

Myocardial infarction (MI), commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia, which is an increasing problem in terms of morbidity, mortality and healthcare costs worldwide. Along with the idea to develop nanocarriers that efficiently deliver therapeutic agents to target the heart, in this study, we aimed to test the in vivo biocompatibility of different sizes of thermally hydrocarbonized porous silicon (THCPSi) microparticles and thermally oxidized porous silicon (TOPSi) micro and nanoparticles in the heart tissue. Despite the absence or low cytotoxicity, both particle types showed good in vivo biocompatibility, with no influence on hematological parameters and no considerable changes in cardiac function before and after MI.

In vivo evaluation of porous silicon and porous silicon solid lipid nanocomposites for passive targeting and imaging.

The use of nanoparticle carriers for the sustained release of cytotoxic drugs in cancer therapy can result in fewer adverse effects and can thus be of great benefit for the patient. Recently, a novel nanocomposite, prepared by the encapsulation of THCPSi nanoparticles within solid lipids (SLN), was developed and characterized as a promising drug delivery carrier in vitro. The present study describes the in vivo evaluation of unmodified THCPSi nanoparticles and THCPSi-solid lipid nanocomposites (THCPSi-SLNCs) as potential drug delivery carriers for cancer therapy by using (18)F radiolabeling for the detection of the particle biodistribution in mice.

Augmented cellular trafficking and endosomal escape of porous silicon nanoparticles via zwitterionic bilayer polymer surface engineering.

The development of a stable vehicle with low toxicity, high cellular internalization, efficient endosomal escape, and optimal drug release profile is a key bottleneck in nanomedicine. To overcome all these problems, we have developed a successful layer-by-layer method to covalently conjugate polyethyleneimine (PEI) and poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of undecylenic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs), forming a bilayer zwitterionic nanocomposite containing free positive charge groups of hyper-branched PEI disguised by the PMVE-MA polymer. The surface smoothness, charge and hydrophilicity of the developed NPs considerably improved the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion.

Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers.

Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin.

Porous silicon nanoparticles for nanomedicine: preparation and biomedical applications.

The research on porous silicon (PSi) materials for biomedical applications has expanded greatly since the early studies of Leigh Canham more than 25 years ago. Currently, PSi nanoparticles are receiving growing attention from the scientific biomedical community. These nanostructured materials have emerged as promising multifunctional and versatile platforms for nanomedicine in drug delivery, diagnostics and therapy.

Comparison of FecalSwab and ESwab devices for storage and transportation of Diarrheagenic bacteria.

Using a collection (n = 12) of ATCC and known stock isolates, as well as 328 clinical stool specimens, we evaluated the ESwab and the new FecalSwab liquid-based microbiology (LBM) devices for storing and transporting diarrheagenic bacteria. The stock isolates were stored in these swab devices up to 48 h at refrigeration (4°C) or room (∼25°C) temperature and up to 3 months at -20°C or -70°C. With the clinical stool specimens, the performances of the ESwab and FecalSwab were compared to those of routinely used transport systems (Amies gel swabs and dry containers).