Dopamine Depletion Reduces Food-Related Reward Activity Independent of BMI.

Reward sensitivity and possible alterations in the dopaminergic-reward system are associated with obesity. We therefore aimed to investigate the influence of dopamine depletion on food-reward processing. We investigated 34 female subjects in a randomized placebo-controlled, within-subject design (body mass index (BMI)=27.0 kg/m(2) ±4.79 SD; age=28 years ±4.97 SD) using an acute phenylalanine/tyrosine depletion drink representing dopamine depletion and a balanced amino acid drink as the control condition. Brain activity was measured with functional magnetic resonance imaging during a 'wanting' and 'liking' rating of food items. Eating behavior-related traits and states were assessed on the basis of questionnaires. Dopamine depletion resulted in reduced activation in the striatum and higher activation in the superior frontal gyrus independent of BMI. Brain activity during the wanting task activated a more distributed network than during the liking task. This network included gustatory, memory, visual, reward, and frontal regions. An interaction effect of dopamine depletion and the wanting/liking task was observed in the hippocampus. The interaction with the covariate BMI was significant in motor and control regions but not in the striatum. Our results support the notion of altered brain activity in the reward and prefrontal network with blunted dopaminergic action during food-reward processing. This effect is, however, independent of BMI, which contradicts the reward-deficiency hypothesis. This hints to the hypothesis suggesting a different or more complex mechanism underlying the dopaminergic reward function in obesity.

Irreversibility of pressure induced boron speciation change in glass.

It is known that the coordination number (CN) of atoms or ions in many materials increases through application of sufficiently high pressure. This also applies to glassy materials. In boron-containing glasses, trigonal BO3 units can be transformed into tetrahedral BO4 under pressure. However, one of the key questions is whether the pressure-quenched CN change in glass is reversible upon annealing below the ambient glass transition temperature (Tg). Here we address this issue by performing (11)B NMR measurements on a soda lime borate glass that has been pressure-quenched at ~0.6 GPa near Tg. The results show a remarkable phenomenon, i.e., upon annealing at 0.9Tg the pressure-induced change in CN remains unchanged, while the pressurised values of macroscopic properties such as density, refractive index, and hardness are relaxing. This suggests that the pressure-induced changes in macroscopic properties of soda lime borate glasses compressed up to ~0.6 GPa are not attributed to changes in the short-range order in the glass, but rather to changes in overall atomic packing density and medium-range structures.

Li diffusion and the effect of local structure on Li mobility in Li2O-SiO2 glasses.

Aimed to improve the understanding of lithium migration mechanisms in ion conductors, this study focuses on Li dynamics in binary Li silicate glasses. Isotope exchange experiments and conductivity measurements were carried out to determine self-diffusion coefficients and activation energies for Li migration in Li2Si3O7 and Li2Si6O13 glasses. Samples of identical composition but different isotope content were combined for diffusion experiments in couples or triples. Diffusion profiles developed between 511 and 664 K were analyzed by femtosecond laser ablation combined with multiple collector inductively coupled plasma mass spectrometry (fs LA-MC-ICP-MS) and secondary ion mass spectrometry (SIMS). Analyses of diffusion profiles and comparison of diffusion data reveal that the isotope effect of lithium diffusion in silicate glasses is rather small, consistent with classical diffusion behavior. Ionic conductivity of glasses was measured between 312 and 675 K. The experimentally obtained self-diffusion coefficient, D(IE), and ionic diffusion coefficient, D(σ), derived from specific DC conductivity provided information about correlation effects during Li diffusion. The D(IE)/D(σ) is higher for the trisilicate (0.27 ± 0.05) than that for the hexasilicate (0.17 ± 0.02), implying that increasing silica content reduces the efficiency of Li jumps in terms of long-range movement. This trend can be rationalized by structural concepts based on nuclear magnetic resonance (NMR) and Raman spectroscopy as well as molecular dynamic simulations, that is, lithium is percolating in low-dimensional, alkali-rich regions separated by a silica-rich matrix.

Optimizing injectable poly-L-lactic acid administration for soft tissue augmentation: The rationale for three treatment sessions.

BACKGROUND: The availability and variety of different injectable modalities has led to a dramatic increase in soft tissue augmentation procedures in recent years. Injectable poly-L-lactic acid (PLLA) is a synthetic, biodegradable polymer device approved in the United States for use in immunocompetent patients as a single regimen of up to four treatment sessions for correction of shallow to deep nasolabial fold contour deficiencies and other facial wrinkles. Injectable PLLA is also approved for restoration and/or correction of signs of facial fat loss (lipoatrophy) in individuals with HIV. METHODS: The present article provides an overview of previous studies with injectable PLLA, and specifically focuses on the number of recommended treatment sessions and intervals between treatment sessions. The authors also provide two case studies to support their recommendations for an average of three treatment sessions. RESULTS: Although the specific mechanisms remain hypothetical, injections of PLLA are believed to cause a cascade of cellular events that lead to collagen repair and subsequent restoration of facial volume. Because the development of a response to injectable PLLA is gradual and its duration of effect is long lasting, sufficient time between treatment sessions should be allocated to avoid overcorrection. CONCLUSION: Studies of injectable PLLA support the hypothesized mode of operation, and the experience and clinical recommendations of the authors that suggest that three treatment sessions are an optimal regimen for use of injectable PLLA in the majority of patients.

A novel quantification of blood-brain barrier damage and histochemical typing after embolic stroke in rats.

Treatment strategies in acute ischemic stroke are still limited. Considering numerous translation failures, research is tending to a preferred use of human-like animal models, and a more-complex perspective of tissue salvaging involving endothelial, glial and neuronal components according to the neurovascular unit (NVU) concept. During ischemia, blood-brain barrier (BBB) alterations lead to brain edema and hemorrhagic transformation affecting NVU components. The present study aims on a novel quantification method of BBB damage and affected tissue following experimental cerebral ischemia, closely to the human condition. Wistar rats underwent embolic middle cerebral artery occlusion, followed by an intravenous application of fluorescein isothiocyanate (FITC)-tagged albumin (≈70kDa) and/or biotinylated rat IgG (≈150kDa) as BBB permeability markers. Both fluorescent agents revealed similar leakage and allow quantification of BBB permeability by fluorescence microscopy, and after immunohistochemical conversion into a permanent diaminobenzidine label at light-microscopical level. The following markers were identified for sufficient detection of NVU components: Rat endothelial cell antigen-1 (RECA) and laminin for vessels, Lycopersicon esculentum and Griffonia simplicifolia agglutinin for vessels and microglial subpopulations, ionized calcium binding adaptor molecule 1 (Iba1), CD68 and CD11b for macrophages, activated microglia, monocytes and neutrophils, S100ß for astroglia, as well as NeuN and HuC/D for neurons. This is the first report confirming the usefulness of simultaneously applied FITC-albumin and biotinylated rat IgG as BBB permeability markers in experimental stroke, and, specifying antibodies and lectins for multiple fluorescence labeling of NVU components. Newly elaborated protocols might facilitate a more-complex outcome measurement in drug development for cerebral ischemia.

Endoscope-assisted submandibular sialadenectomy: a review of outcomes, complications, and ethical concerns.

OBJECTIVES: To review outcomes and complications of endoscope-assisted submandibular sialadenectomy (EASS) and to analyze this innovative technique with regard to ethical issues. METHODS: We used a systematic review study design to identify clinical studies on EASS, published in English, French, German, and Thai. The last electronic search was conducted in September 2009. We checked the bibliographies of the identified articles, relevant local journals, and congress abstracts. Publications were further assessed and assigned their respective levels of evidence. We also investigated reporting on human subject protection, conflicts of interest, funding support, and commercial relationships. RESULTS: Five case series reporting a total of 28 patients met the inclusion criteria. There was no need of recourse to open surgery. All of the authors claimed satisfactory cosmetic results. Complications were uncommon. However, no controlled trial was available, and outcome measures varied between studies. Human subject protection and funding sources were mentioned in only 2 articles. Commercial relationships and conflicts of interest could not be identified. CONCLUSIONS: All of the reports favor outcomes of EASS. However, their level of evidence is low, and the superiority of this procedure over the conventional surgery remains unknown. The success of this procedure should not be overemphasized in information for consent and mislead surgeons to begin it without adequate training and elaborate environment. The lack of ethical documentation creates a high degree of suspicion of the studies.

Ethical issues in instructions to authors of journals in oral-craniomaxillofacial/facial plastic surgery and related specialties.

BACKGROUND: Ethical standards of biomedical publications are associated with editorial leadership, such as contents of instructions to authors and journal's mechanisms for research and publication ethics. OBJECTIVES: To compare ethical issues in the guidelines for authors in oral-craniomaxillofacial/facial plastic surgery (OCM-FPS) journals with those in plastic surgery and otorhinolaryngology/head and neck surgery (ORL-HNS) journals, and to evaluate the relationship between journal's impact factor (IF) and ethical issues in the instructions to authors. METHODS: This study used a cross-sectional study design. The predictor variables were journal's specialty and IF. The outcome variable was the presence of seven ethical issues in the online versions of journal's instructions to authors in October 2009. We included only journals with identifiable IF for 2008, published in English, French, German and Thai. Appropriate descriptive and univariate statistics were computed for all study variables. The level of statistical significance was set at P<0.05. RESULTS: The sample was composed of 48 journals: seven OCM-FPS (14.6%), 14 plastic surgery (29.2%) and 27 ORL-HNS (56.2%) journals. Only four journals (8.3%) mentioned all ethical issues in their guidelines for authors. Neither journal's specialty nor IF was linked to completeness of the ethical requirements. CONCLUSIONS: The results of this study suggest that ethical issues in the instructions to authors of most IF-indexed journals in OCM-FPS, plastic surgery and ORL-HNS are incomplete, regardless of specialty and IF. There is room for substantial improvement to uphold scientific integrity of these surgical specialties.

Slow age-dependent decline of doublecortin expression and BrdU labeling in the forebrain from lesser hedgehog tenrecs.

In addition to synaptic remodeling, formation of new neurons is increasingly acknowledged as an important cue for plastic changes in the central nervous system. Whereas all vertebrates retain a moderate neuroproliferative capacity, phylogenetically younger mammals become dramatically impaired in this potential during aging. The present study shows that the lesser hedgehog tenrec, an insectivore with a low encephalization index, preserves its neurogenic potential surprisingly well during aging. This was shown by quantitative analysis of 5-bromo-2'-deoxyuridine (BrdU) immunolabeling in the olfactory bulb, paleo-, archi-, and neocortices from 2- to 7-year-old animals. In addition to these newly born cells, a large number of previously formed immature neurons are present throughout adulthood as shown by doublecortin (DCX) immunostaining in various forebrain regions including archicortex, paleocortex, nucleus accumbens, and amygdala. Several ventricle-associated cells in olfactory bulb and hippocampus were double-labeled by BrdU and DCX immunoreactivity. However, most DCX cells in the paleocortex can be considered as persisting immature neurons that obviously do not enter a differentiation program since double fluorescence labeling does not reveal their co-occurrence with numerous neuronal markers, whereas only a small portion coexpresses the pan-neuronal marker HuC/D. Finally, the present study reveals tenrecs as suitable laboratory animals to study age-dependent brain alterations (e.g., of neurogenesis) or slow degenerative processes, particularly due to the at least doubled longevity of tenrecs in comparison to mice and rats.

Concomitant detection of beta-amyloid peptides with N-terminal truncation and different C-terminal endings in cortical plaques from cases with Alzheimer's disease, senile monkeys and triple transgenic mice.

The disturbed metabolism of beta-amyloid peptides generated from amyloid precursor protein is widely considered as a main factor during the pathogenesis of Alzheimer's disease. A neuropathological hallmark in the brains from cases with Alzheimer's disease are senile plaques mainly composed of hardly soluble beta-amyloid peptides comprising up to 43 amino acids. Age-dependent cortical beta-amyloidosis was also shown in several transgenic mice and old individuals from various mammalian species, e.g., non-human primates. Beta-amyloid(1-42) is believed to be the main component in the core of senile plaques, whereas less hydrophobic beta-amyloid(1-40) predominantly occurs in the outer rim of plaques. Amino-terminally truncated pyroglutamyl-beta-amyloid(pE3-x) was recently found to be a beta-amyloid species of high relevance to the progression of the disease. While a few biochemical studies provided data on the co-occurrence of several beta-amyloid forms, their concomitant histochemical detection is still lacking. Here, we present a novel triple immunofluorescence labelling of amino- and differently carboxy-terminally truncated beta-amyloid peptides in cortical plaques from a case with Alzheimer's disease, senile macaques and baboons, and triple transgenic mice with age-dependent beta-amyloidosis and tau hyperphosphorylation. Additionally, beta-amyloid(pE3-x) and total beta-amyloid were concomitantly detected with beta-amyloid peptides ending with amino acid 40 or 42, respectively. Simultaneous staining of several beta-amyloid species reveals for instance vascular amyloid containing beta-amyloid(pE3-x) in Alzheimer's disease and monkeys, and may contribute to the further elucidation of beta-amyloidosis in neurodegenerative disorders and animal models.

In vivo labelling of hippocampal beta-amyloid in triple-transgenic mice with a fluorescent acetylcholinesterase inhibitor released from nanoparticles.

The drastic loss of cholinergic projection neurons in the basal forebrain is a hallmark of Alzheimer's disease (AD), and drugs most frequently applied for the treatment of dementia include inhibitors of the acetylcholine-degrading enzyme acetylcholinesterase (AChE). This protein is known to act as a ligand of beta-amyloid (Abeta) in senile plaques, a further neuropathological sign of AD. Recently, we have shown that the fluorescent, heterodimeric AChE inhibitor PE154 allows for the histochemical staining of cortical Abeta plaques in triple-transgenic (TTG) mice with age-dependent beta-amyloidosis and tau hyperphosphorylation, an established animal model for aspects of AD. In the present study, we have primarily demonstrated the targeting of Abeta-immunopositive plaques with PE154 in vivo for 4 h up to 1 week after injection into the hippocampi of 13-20-month-old TTG mice. Numerous plaques, double-stained for PE154 and Abeta-immunoreactivity, were revealed by confocal laser-scanning microscopy. Additionally, PE154 targeted hippocampal Abeta deposits in aged TTG mice after injection of carboxylated polyglycidylmethacrylate nanoparticles delivering the fluorescent marker in vivo. Furthermore, biodegradable core-shell polystyrene/polybutylcyanoacrylate nanoparticles were found to be suitable, alternative vehicles for PE154 as a useful in vivo label of Abeta. Moreover, we were able to demonstrate that PE154 targeted Abeta, but neither phospho-tau nor reactive astrocytes surrounding the plaques. In conclusion, nanoparticles appear as versatile carriers of AChE inhibitors and other promising drugs for the treatment of AD.

Swine-origin H1N1 influenza A virus and dental practice: a critical review.

Since the spring of 2009, there have been a considerable number of infected as well as fatal cases by virologically confirmed swine-origin H1N1 influenza A virus (S-OIV). The virus continues to spread globally. The World Health Organization (WHO) has now raised the level of S-OIV influenza pandemic alert to phase 6 ('the pandemic phase') because of the human-to-human transmission of the virus and the community-level outbreaks worldwide. The WHO also issues its concerns about the global surveillance, the diagnostic capacity for the infection and the pandemic preparedness plan in every country. However, no critical review on S-OIV influenza and dental practice published in the literature exists hitherto. Based on information up to November 2009, the aim of this article was to summarise significant data on this novel virus and a clinical practice guideline for dental professionals.

Publication bias in oral and maxillofacial surgery journals: an observation on published controlled trials.

BACKGROUND: Publication bias (PB) diminishes the full distribution of research, distorts and discredits the scientific record, and thus compromises evidence-based practice. The objective of this study was to analyse published controlled trials with regard to PB in leading oral and maxillofacial surgery (OMS) journals. METHODS: All controlled trials published in the International Journal of Oral and Maxillofacial Surgery, Journal of Cranio-Maxillofacial Surgery, Journal of Oral and Maxillofacial Surgery, and British Journal of Oral and Maxillofacial Surgery in 2008 were analysed for a primary outcome, country of authors, sample size, gender of the first author, funding source and location of the study. RESULTS: Of 952 published articles, 53 controlled trials (5.7%) were identified. The OMS journals preferentially published controlled trials with a positive outcome (77.4%) and from high-income countries (73.6%). Single-centred trials (86.8%) with low sample size (n<100; 69.8%) were published more frequently. The majority of the first authors were male (75.5%). Funding source disclosure was missing in most studies (73.6%) [corrected]. CONCLUSIONS: Our results suggest the possible existence of PB in the OMS literature. Hence, it should be borne in mind that the published articles may not be representative of all scientific works, especially when systematic reviews and meta-analyses are conducted or read. In the meantime, journals should establish measures to eliminate PB to uphold scientific integrity. However, this study was an observation based on the published articles. An analysis of all submitted manuscripts would provide more accurate estimates of PB. Ethical considerations on PB are also discussed.

Pathogen specific cytokine release reveals an effect of TLR2 Arg753Gln during Candida sepsis in humans.

Toll-like receptors (TLRs) are crucial pattern-recognition receptors (PRRs) for activation of innate and adapted immunity. TLR2 heterodimerizes with TLR1 or TLR6 to recognize multiple pathogen-associated molecular patterns (PAMPs) of fungi, Gram-positive pathogens, and mycobacteria. Receptor activation culminates in monocyte, T-helper (Th)1, and Th2 cytokine release. Single nucleotide polymorphisms (SNPs) Arg753Gln and Arg677Trp affect TLR2 responsiveness and may contribute to the course of sepsis, which is associated with substantial morbidity and mortality during intensive care treatment. We genotyped 325 critically ill patients with septic shock, and performed a detailed clinical follow-up with 47 of these patients. Here, we investigated whether distinct sepsis episodes result in defined plasma cytokine patterns, and whether cytokine profiles may be linked to the TLR2 polymorphisms. Blood sampling was done daily and microbiological testing was performed on a routine basis. DNA was extracted from whole blood and TLR2 SNPs were typed by pyrosequencing. Cytokines were measured by multiplexed array technologies and the leukocyte phenotype was determined by flow cytometry. Among the 325 ICU patients, 17 individuals (5.2%) were heterozygous for Arg753Gln. The SNP Arg677Trp was not found in any patient. Episodes of Gram-negative, Gram-positive, and Candida sepsis were recorded. During Gram-positive sepsis, the cytokine pattern did not differ between Arg753Gln heterozygous patients and wild type patients. By contrast, during Candida sepsis, the Arg753Gln heterozygous patients showed biomarker patterns that differed from wild type patients with elevated TNF-alpha plasma concentrations, but reduced IFN-gamma and IL-8 levels. In conclusion, TLR2 SNP Arg753Gln results in altered cytokine release in response to Candida but not to Gram-positive sepsis.

Full scope of effect of facial lipoatrophy: a framework of disease understanding.

BACKGROUND: Facial lipoatrophy has been observed to occur in a variety of patient populations, with inherited or acquired disease, or even in aging patients as a natural progression of tissue change over time. There is currently no framework from which physicians of all medical specialties can communally discuss the manifestations, diagnoses, and management of facial lipoatrophy. OBJECTIVE: The aim of this assembly was to derive a definition of facial lipoatrophy capable of being applied to all patient populations and develop an accompanying grading system. RESULTS: The final consensus of the Facial Lipoatrophy Panel encompasses both aging and disease states: "Loss of facial fat due to aging, trauma or disease, manifested by flattening or indentation of normally convex contours." The proposed grading scale includes five gradations (Grades 1-5; 5 being the most severe), and the face is assessed according to three criteria: contour, bony prominence, and visibility of musculature. CONCLUSION: Categorizing the presentation of facial lipoatrophy is subjective and qualitative, and will need to be validated with objective measures. Furthermore, during the assembly, several topics were exposed that warrant further research, including the physiology of volume loss, age and lipoatrophy, and human immunodeficiency virus and lipoatrophy.

Use of polylactic acid implants to correct facial lipoatrophy in human immunodeficiency virus 1-positive individuals receiving combination antiretroviral therapy.

OBJECTIVE: To assess the efficacy, safety, and tolerability of facial injections of polylactic acid for human immunodeficiency virus (HIV) 1-associated facial lipoatrophy, which commonly affects HIV-1-infected patients receiving combination antiretroviral therapy. DESIGN: A cohort of 50 consecutive HIV-1-infected outpatients with moderate to severe facial lipoatrophy who were receiving antiretroviral therapy were recruited in one institutional center and followed up for 12 months. Patients received the compound subcutaneously at baseline and on days 30, 45, and 60 of the study, for a total of 4 sets of injections; if necessary, 2 additional sets of injections were allowed on days 75 and 90. At enrollment and during follow-up, data on patients' characteristics, facial ultrasonography, and iconography were assessed. Data for 2 questionnaires, on self-perception of severity of facial lipoatrophy and on quality of life measured by the Medical Outcomes Study-HIV, were also obtained. RESULTS: Polylactic acid injections led to a significant improvement in facial lipoatrophy, confirmed by the patients' facial lipoatrophy self-perception and by the ultrasonographic evaluation. The mean total cutaneous thickness of each cheek increased significantly between baseline and after completing the polylactic acid injection sessions (4.3 mm [range, 2.7-6.2 mm] [P<.001] and 4.4 mm [range, 2.7-6.1 mm] [P<.001] on the right and left cheeks, respectively) and persisted significantly until month 12 of follow-up (3.4 mm [range, 2.3-4.9 mm] [P<.001] and 3.3 mm [range, 1.6-5.0 mm] [P<.001] on the right and left cheeks, respectively). In addition, a significant (P<.01) improvement in overall quality of life was observed between baseline and the end of the study. No patients discontinued treatment because of toxic effects, and subcutaneous micronodules at the site of injection were never observed. CONCLUSIONS: Polylactic acid injections can be considered an effective, safe, and simple procedure in HIV-related facial lipoatrophy. The overall improvement of quality of life was clearly associated with the correction of lipoatrophy, reflecting the positive effect of this strategy on patient well-being.

Facial enhancement and the European experience with Sculptra (poly-l-lactic acid).

The primary reason patients seek aesthetic treatments is to combat the signs of aging. However, the majority of facial treatments and procedures fill specific wrinkles or pull-taught sagging skin, without returning the volume and contours of a youthful face. Injectable poly-L-lactic acid (Sculptra) is a synthetic, biodegradable polymer, popular in Europe for the correction of lipoatrophy. The novel technique and mechanism of action of this product require physicians to adjust their practice of treating a specific line to returning volume to a facial area. Sculptra has been used successfully for the correction of nasolabial folds, mid and lower facial volume loss, jaw line laxity, and other signs of facial aging. Sculptra treatment provides a minimally invasive, effective, and prolonged (18-24 months) facial enhancement correction with a low frequency of side effects and no need for allergy testing.

Comparative proteomic analysis of proliferating and functionally differentiated mammary epithelial cells.

Proliferation and differentiation of mammary epithelial cells are governed by hormonal stimuli, cell-cell, and cell-matrix interactions. Terminal differentiation of mammary epithelial cells depends upon the action of the lactogenic hormones, insulin, glucocorticoids, and prolactin that enable them to synthesize and secrete milk proteins. These differentiated cells are polarized and carry out vectorial transport of milk constituents across the apical plasma membrane. To gain additional insights into the mechanisms governing differentiation of mammary epithelial cells, we identified proteins whose expression distinguishes proliferating from differentiated mammary epithelial cells. For this purpose we made use of the HC11 mammary epithelial line, which is capable of differentiation in response to lactogenic hormones. Using two-dimensional gel electrophoresis and mass spectrometry, we found about 60 proteins whose expression levels changed in between these two differentiation states. Bioinformatic analysis revealed differential expression of cytoskeletal components, molecular chaperones and regulators of protein folding and stability, calcium-binding proteins, and components of RNA-processing pathways. The actin cytoskeleton is asymmetrically distributed in differentiated epithelial cells, and the identification of proteins involved in mRNA binding and localization suggests that asymmetry might in part be achieved by controlling cellular localization of mRNAs. The proteins identified provide insights into the differentiation of mammary epithelial cells and the regulation of this process.