Search

Antidepressant drugs play a crucial role in the treatment of mental health disorders, but their efficacy and safety can be compromised by drug degradation. Recent reports point to several drugs found in concentrations ranging from the limit of detection (LOD) to hundreds of ng/L in wastewater plants around the globe; hence, antidepressants can be considered emerging pollutants with potential consequences for human health and wellbeing. Understanding and implementing effective degradation strategies are essential not only to ensure the stability and potency of these medications but also for their safe disposal in line with current environment remediation goals. This review provides an overview of degradation pathways for amitriptyline, a typical tricyclic antidepressant drug, by exploring chemical routes such as oxidation, hydrolysis, and photodegradation. Connex issues such as stability-enhancing approaches through formulation and packaging considerations, regulatory guidelines, and quality control measures are also briefly noted. Specific case studies of amitriptyline degradation pathways forecast the future perspectives and challenges in this field, helping researchers and pharmaceutical manufacturers to provide guidelines for the most effective degradation pathways employed for minimal environmental impact.

There is a growing evidence that methylation at the N6 position of adenine (6-mA), whose modulation occurs primarily during development, would be a reliable epigenetic marker in eukaryotic organisms. The present study raises the question as to whether early-life exposure to α-hexabromocyclododecane (α-HBCDD), a brominated flame retardant, may trigger modifications in 6-mA epigenetic hallmarks in the brain during the development which, in turn could affect the offspring behaviour in adulthood. Pregnant Wistar rats were split into two groups: control and α-HBCDD (66 ng/kg/per os, G0-PND14). At PND1, α-HBCDD levels were assessed in brain and liver by LC-MS/MS. At PND14, DNA was isolated from the offspring’s cerebellum. DNA methylation was measured by 6-mA-specific immunoprecipitation and Illumina® sequencing (MEDIP-Seq). Locomotor activity was finally evaluated at PND120. In our early-life exposure model, we confirmed that α-HBCDD can cross the placental barrier and be detected in pups at birth. An obvious post-exposure phenotype with locomotor deficits was observed when the rats reached adulthood. This was accompanied by sex-specific over-methylation of genes involved in the insulin signaling pathway, MAPK signaling pathway as well as serotonergic and GABAergic synapses, potentially altering the normal process of neurodevelopment with consequent motor impairments crystalized at adulthood.

Background and objectives: eNAMPT (extracellular nicotinamide phosphoribosyltransferase), a novel DAMP and TLR4 ligand, is a druggable ARDS therapeutic target with NAMPT promoter SNPs associated with ARDS severity. This study assesses the previously unknown influence of NAMPT promoter SNPs on NAMPT transcription, eNAMPT secretion, and ARDS severity. Methods and design: Human lung endothelial cells (ECs) transfected with NAMPT promoter luciferase reporters harboring SNPs G-1535A, A-1001 C, and C-948A, were exposed to LPS or LPS/18% cyclic stretch (CS) and NAMPT promoter activity, NAMPT protein expression, and secretion assessed. NAMPT genotypes and eNAMPT plasma measurements (Days 0/7) were assessed in two ARDS cohorts (DISCOVERY n = 428; ALVEOLI n = 103). Results: Comparisons of minor allelic frequency (MAF) in both ARDS cohorts with the 1000 Human Genome Project revealed the G-1535A and C-948A SNPs to be significantly associated with ARDS in Blacks compared with controls and trended toward significance in non-Hispanic Whites. LPS-challenged and LPS/18% CS–challenged EC harboring the -1535G wild-type allele exhibited significantly increased NAMPT promoter activity (compared with -1535A) with the -1535G/-948A diplotype exhibiting significantly increased NAMPT promoter activity, NAMPT protein expression, and eNAMPT secretion compared with the -1535A/-948 C diplotype. Highly significant increases in Day 0 eNAMPT plasma values were observed in both DISCOVERY and ALVEOLI ARDS cohorts (compared with healthy controls). Among subjects surviving to Day 7, Day 7 eNAMPT values were significantly increased in Day 28 non-survivors versus survivors. The protective -1535A SNP allele drove -1535A/-1001A and -1535A/-948 C diplotypes that confer significantly reduced ARDS risk (compared with -1535G, -1535G/-1001 C, -1535G/-948A), particularly in Black ARDS subjects. NAMPT SNP comparisons within the two ARDS cohorts did not identify significant association with either APACHE III scores or plasma eNAMPT levels. Conclusion: NAMPT SNPs influence promoter activity, eNAMPT protein expression/secretion, plasma eNAMPT levels, and ARDS severity. NAMPT genotypes are a potential tool for stratification in eNAMPT-focused ARDS clinical trials.

Abstract Background Nicotinamide phosphoribosyltransferase (NAMPT) exhibits dual functionality – as an intracellular enzyme regulating nicotinamide adenine dinucleotide metabolism and as an extracellular secreted protein (eNAMPT) to function as a cytokine regulator of innate immunity via binding to Toll-Like receptor 4 and NF-κB activation. In limited preclinical and clinical studies, eNAMPT was implicated in the pathobiology of acute respiratory distress syndrome (ARDS) suggesting that eNAMPT could potentially serve as a diagnostic and prognostic biomarker. We investigated the feasibility of circulating eNAMPT levels to serve as a biomarker in an expanded cohort of patients with ARDS and ARDS-predisposing conditions that included acute pancreatitis, sepsis, and trauma with comparisons to controls. Methods A total of 671 patients and 179 healthy controls were included in two independent cohorts. Plasma and serum eNAMPT levels were quantified using one of two complementary Enzyme-linked Immunosorbent Assays. After log base 2 variance stabilizing transformation of plasma/serum eNAMPT measurements, differences between healthy controls and each disease cohort were compared using linear regression or a generalized estimating equation (GEE) model where applicable. Complementary analyses included sensitivity, specificity, positive predictive values, negative predictive values, and the area under the receiver operating curve. Results Compared to controls, circulating eNAMPT levels were significantly elevated in subjects with acute pancreatitis, sepsis, trauma, and ARDS (all p

Tricyclic antidepressants are commonly employed in the management of major depressive disorders. The present work describes two visible (VIS) spectrophotometric techniques that utilize the formation of charge transfer complexes between four antidepressant compounds, namely, amitriptyline hydrochloride (AMI), imipramine hydrochloride (IMI), clomipramine hydrochloride (CLO), and trimipramine maleate (TRI) acting as electron donors and two p-benzoquinones, namely, p-chloranilic acid (pCA) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), serving as electron acceptors. The stoichiometry of the compounds produced exhibited a consistent 1:1 ratio in all instances, as established by Job’s method. Molar absorptivities, equilibrium association constants, and several other spectroscopic properties were determined for all complexes. The developed spectrophotometric techniques were validated intra-laboratory and successfully applied for quantitative assessment of the four antidepressant active ingredients in several commercial pharmaceutical formulations. The methods are relatively simple, fast, and use readily available laboratory instrumentation, making them easily applicable by most quality control laboratories worldwide.

BackgroundProgressive pulmonary fibrosis is a serious complication in subjects with sarcoidosis. The absence of reliable, non-invasive biomarkers that detect early progression exacerbates the difficulty in predicting sarcoidosis severity. To potentially address this unmet need, we evaluated a panel of markers for an association with sarcoidosis progression (HBEGF, NAMPT, IL1-RA, IL-6, IL-8, ANG-2). This panel encompasses proteins related to inflammation, vascular injury, cell proliferation, and fibroblast mitogenesis processes.MethodsPlasma biomarker levels and biomarker protein expression in lung and lymph nodes tissues (immunohistochemical studies) from sarcoidosis subjects with limited disease and progressive (complicated) sarcoidosis were performed. Gene expression of the protein-coding genes included in this panel was analyzed using RNAseq in sarcoidosis granulomatous tissues from lung and lymph nodes.ResultsExcept for IL-8, plasma levels of each biomarker—eNAMPT, IL-1RA, IL-6, ANG-2, and HBEGF—were significantly elevated in sarcoidosis subjects compared to controls. In addition, plasma levels of HBEGF were elevated in complicated sarcoidosis, while eNAMPT and ANG-2 were observed to serve as markers of lung fibrosis in a subgroup of complicated sarcoidosis. Genomic studies corroborated HBEGF and NAMPT among the top dysregulated genes and identified cytokine-related and fibrotic pathways in lung granulomatous tissues from sarcoidosis.ConclusionThese findings suggest HBEGF, eNAMPT, and ANG-2 may serve as potential novel indicators of the clinical severity of sarcoidosis disease.

Electrophysiological mapping (EM) using acute electrode probes is a common procedure performed during functional neurosurgery. Due to their constructive specificities, the EM probes are lagging in innovative enhancements. This work addressed complementing a clinically employed EM probe with carbonic and circumferentially segmented macrocontacts that are operable both for neurophysiological sensing (“recording”) of local field potentials (LFP) and for test stimulation. This paper illustrates in-depth the development that is based on the direct writing of functional materials. The unconventional fabrication processes were optimized on planar geometry and then transferred to the cylindrically thin probe body. We report and discuss the constructive concept and architecture of the probe, characteristics of the electrochemical interface deduced from voltammetry and chronopotentiometry, and the results of in vitro and in vivo recording and pulse stimulation tests. Two- and three-directional macrocontacts were added on probes having shanks of 550 and 770 μm diameters and 10–23 cm lengths. The graphitic material presents a ~2.7 V wide, almost symmetric water electrolysis window, and an ultra-capacitive charge transfer. When tested with clinically relevant 150 μs biphasic current pulses, the interfacial polarization stayed safely away from the water window for pulse amplitudes up to 9 mA (135 μC/cm2). The in vivo experiments on adult rat models confirmed the high-quality sensing of LFPs. Additionally, the in vivo-prevailing increase in the electrode impedance and overpotential are discussed and modeled by an ionic mobility-reducing spongiform structure; this restricted diffusion model gives new applicative insight into the in vivo-uprisen stimulation overpotential.

Microemulsions are nanocolloidal systems composed of water, an oil, and a surfactant, sometimes with an additional co-surfactant, which have found a wide range of practical applications, including the extractive removal of contaminants from polluted water. In this study, microemulsion systems, including a nonionic surfactant (Brij 30), water, and esters selected from two homologous series of C1–C6 alkyl acetates and ethyl C1–C4 carboxylates, respectively, were prepared by the surfactant titration method. Phase transitions leading to the formation of Winsor II and Winsor IV microemulsions were observed and phase diagrams were constructed. The dependences of phase transitions on the salinity and pH and the addition of isopropanol as a co-surfactant were also investigated. Some physical properties, namely density, refractive index, electrical conductivity, dynamic viscosity, and particle size, were measured for a selection of Winsor IV microemulsions, providing further insight into some other phase transitions occurring in the monophasic domains of phase diagrams. Finally, Winsor II microemulsions were tested as extraction solvents for the removal of four tricyclic antidepressant drugs from aqueous media. Propyl acetate/Brij 30/H2O microemulsions provided the best extraction yields (>90%), the highest Nernst distribution coefficients (~40–88), and a large volumetric ratio of almost 3 between the recovered purified water and the resulting microemulsion extract. Increasing the ionic strength (salinity) or the pH of the aqueous antidepressant solutions led to an improvement in extraction efficiencies, approaching 100%. These results could be extrapolated to other classes of pharmaceutical contaminants and suggest ester- and nonionic surfactant-based microemulsions are a promising tool for environmental remediation.

Curcumin is the principal curcuminoid found in the rhizomes of turmeric. Due to its therapeutic action against cancer, depression, diabetes, some bacteria, and oxidative stress, it has been used widely in medicine since ancient times. Due to its low solubility, the human organism cannot completely absorb it. Advanced extraction technologies, followed by encapsulation in microemulsion and nanoemulsion systems, are currently being used to improve bioavailability. This review discusses the different methods available for curcumin extraction from plant material, methods for the identification of curcumin in the resulting extracts, its beneficial effects on human health, and the encapsulation techniques into small colloidal systems that have been used over the past decade to deliver this compound.

Abstract Background There is a compelling unmet medical need for biomarker-based models to risk-stratify patients with acute respiratory distress syndrome. Effective stratification would optimize participant selection for clinical trial enrollment by focusing on those most likely to benefit from new interventions. Our objective was to develop a prognostic, biomarker-based model for predicting mortality in adult patients with acute respiratory distress syndrome. Methods This is a secondary analysis using a cohort of 252 mechanically ventilated subjects with the diagnosis of acute respiratory distress syndrome. Survival to day 7 with both day 0 (first day of presentation) and day 7 sample availability was required. Blood was collected for biomarker measurements at first presentation to the intensive care unit and on the seventh day. Biomarkers included cytokine-chemokines, dual-functioning cytozymes, and vascular injury markers. Logistic regression, latent class analysis, and classification and regression tree analysis were used to identify the plasma biomarkers most predictive of 28-day ARDS mortality. Results From eight biologically relevant biomarker candidates, six demonstrated an enhanced capacity to predict mortality at day 0. Latent-class analysis identified two biomarker-based phenotypes. Phenotype A exhibited significantly higher plasma levels of angiopoietin-2, macrophage migration inhibitory factor, interleukin-8, interleukin-1 receptor antagonist, interleukin-6, and extracellular nicotinamide phosphoribosyltransferase (eNAMPT) compared to phenotype B. Mortality at 28 days was significantly higher for phenotype A compared to phenotype B (32% vs 19%, p = 0.04). Conclusions An adult biomarker-based risk model reliably identifies ARDS subjects at risk of death within 28 days of hospitalization.

The growing demand for more sustainable, alternative processes leading to production of plant-derived preparations imposes the use of plants waste generated mainly by agri-food and pharmaceutical industries. These mostly unexploited but large quantities of plants waste also increase the interest in developing alternative approaches for sustainable production of therapeutic molecules. In order to reduce the amount of plant waste by further processing, different novel extraction techniques can be applied. Fruits and their industrial by-products are rich sources of different classes of compounds with therapeutic properties. The processed fruits waste can be reused and lead to novel pharmaceuticals, food supplements or functional foods. This review intends to briefly summarize recent aspects regarding the production of different active compounds from fruit by-products, and their therapeutic properties. The potential use of fruits by-products in different industries will be also discussed.

Groups of amino acids, and some selected amino acids, added to media used for culture of pre-implantation embryos have previously been shown to improve development in various ways including survival to the blastocyst stage, increased blastocyst cell number and improved hatching. In this study, we cultured 1-cell mouse embryos for 5 days to the hatching blastocyst stage in isosmotic medium (270 mOsm/kg) at high density (10 embryos/10 μL), where autocrine/paracrine support of development occurs, and low density (1 embryo/100 μL), where autocrine/paracrine support is minimized and development is compromised. When 400 μM L-Pro or 1 mM L-Gln was added to embryos at low density, the percentage of embryos reaching the blastocyst stage and the percentage hatching increased compared to low-density culture without these amino acids, and were now similar to those for embryos cultured at high density without amino acids. When L-Pro or L-Gln was added to embryos at high density, the percentage of embryos reaching the blastocyst stage didn’t change but hatching improved. Neither embryo culture density nor the presence of these amino acids had any effect on blastocyst cell number. D-Pro and the osmolytes Gly and Betaine did not improve embryo development in low- or high-density culture indicating the mechanism was stereospecific and not osmotic, respectively. L-Pro- and L-Gln-mediated improvement in development is observed from the 5-cell stage and persists to the blastocyst stage. Molar excess of Gly, Betaine or L-Leu over L-Pro eliminated improvement in development and hatching consistent with them acting as competitive inhibitors of transporter-mediated uptake across the plasma membrane. The L-Pro effect is dependent on mTORC1 signaling (rapamycin sensitive) while that for L-Gln is not. The addition of L-Pro leads to significant nuclear translocation of p-AktS473 at the 2- and 4-cell stages and of p-ERK1/2T202/Y204 nuclear translocation at the 2-, 4-, and 8-cell stages. L-Pro improvement in embryo development involves mechanisms analogous to those seen with Pro-mediated differentiation of mouse ES cells, which is also stereoselective, dependent on transporter uptake, and activates Akt, ERK, and mTORC1 signaling pathways.

Locally advanced larynx cancer benefits from curative surgery therapy. Clinical trials have been proposed for assessing the quality of life for patients with larynx malignant neoplasia who underwent radical surgery. The removal of the “voice box” is known to have great impact on the social reintegration of these patients as well as psychological distress. The presence of tracheostomy and voice impairment are two of the major issues that need to be thought of by patients that will have a total laryngectomy. The quality of life is a multi-dimensional subjective and personal concept which includes normal physical activity, looks, psychological status, somatic symptoms and, non the less, sexual activity. Cancer free survival intervals for patients with larynx cancer must be evaluated physical and psychological modifications with particular considerations to stress, anxiety and depression related symptoms and to functional rehabilitation adaptation regarding swallowing and speech. Oncology surgeons must consider that QoL is impaired in all patients with larynx cancer that benefit from total laryngectomy. However, there is evidence presented below that the difference in QoL parameters is small when comparing radical surgery, total laryngectomy, and larynx conservation by radio and chemotherapy.

The incidence of thyroid cancer is significantly different between male and female patients. Thyroid cancer is also the only form of cancer where age can be considered a staging variable. Identifying biological prognostic factors such as age or sex is important as it helps select an optimal personalized therapy. The present analysis is an observational, prospective study that enrolled all patients with thyroid disease who were operated upon at a single center. The study aimed to determine the most frequent age at presentation, the predominance of one sex over the other, the incidence of malignant thyroid disease, and the relative risk for each sex to develop thyroid carcinoma. The incidence of thyroid carcinoma was higher for women than for men, with a higher relative risk in the female subgroup. Incidence was also highest in the 50-60-year-old group. Given that studies show better survival for women and for younger patients, even when presenting with advanced disease, compared with older, male patients, such prognostic indicators should be a factor in the treatment decision.

Microsatellite instability (MSI) is a feature of colorectal tumors that develops as a result of inactivation of the DNA mismatch repair system. It is found in about 15% of all colorectal cancers and is an important prognostic molecular marker when assessing patients with colorectal cancer. It can influence prognosis and treatment decisions in both the advanced and early stages. Although in early stages this marker suggests a favorable prognosis and presents an important argument against adjuvant treatment in stage II disease, in metastatic stages it no longer associated with such an optimistic outcome. The present trial is a prospective, single-center study which included 122 colorectal cancer patients who were tested for MSI using immunohistochemistry. The trial included patients with stage II to IV colorectal cancer, treated in the Prof. Dr. Agrippa Ionescu Emergency Hospital, Bucharest, Romania. Follow-up data were collected during a 24-month period. The study attempted to determine whether differences exist in overall survival for MSI (microsatellite instability) vs. MSS (microsatellite stable) colorectal cancer and to ascertain whether sex of the patient influences prognosis in MSI patients, irrespective of stage or treatment. Results demonstrated no significant differences in survival for MSI vs MSS colorectal patients, and patients’ gender proved not to influence the outcome in MSI patients.

Abstract Background Subtle DNA methylation alterations mediated by carbon nanotubes (CNTs) exposure might contribute to pathogenesis and disease susceptibility. It is known that both multi-walled carbon nanotubes (MWCNTs) and single-walled carbon nanotubes (SWCNTs) interact with nucleus. Such, nuclear-CNT interaction may affect the DNA methylation effects. In order to understand the epigenetic toxicity, in particular DNA methylation alterations, of SWCNTs and short MWCNTs, we performed global/genome-wide, gene-specific DNA methylation and RNA-expression analyses after exposing human bronchial epithelial cells (16HBE14o- cell line). In addition, the presence of CNTs on/in the cell nucleus was evaluated in a label-free way using femtosecond pulsed laser microscopy. Results Generally, a higher number of SWCNTs, compared to MWCNTs, was deposited at both the cellular and nuclear level after exposure. Nonetheless, both CNT types were in physical contact with the nuclei. While particle type dependency was noticed for the identified genome-wide and gene-specific alterations, no global DNA methylation alteration on 5-methylcytosine (5-mC) sites was observed for both CNTs. After exposure to MWCNTs, 2398 genes were hypomethylated (at gene promoters), and after exposure to SWCNTs, 589 CpG sites (located on 501 genes) were either hypo- (N = 493 CpG sites) or hypermethylated (N = 96 CpG sites). Cells exposed to MWCNTs exhibited a better correlation between gene promoter methylation and gene expression alterations. Differentially methylated and expressed genes induced changes (MWCNTs > SWCNTs) at different cellular pathways, such as p53 signalling, DNA damage repair and cell cycle. On the other hand, SWCNT exposure showed hypermethylation on functionally important genes, such as SKI proto-oncogene (SKI), glutathione S-transferase pi 1 (GTSP1) and shroom family member 2 (SHROOM2) and neurofibromatosis type I (NF1), which the latter is both hypermethylated and downregulated. Conclusion After exposure to both types of CNTs, epigenetic alterations may contribute to toxic or repair response. Moreover, our results suggest that the observed differences in the epigenetic response depend on particle type and differential CNT-nucleus interactions.

The present study examines the impact of a novel online video lecture archiving system on in-class students enrolled in traditional math courses at a mid-sized, primarily undergraduate, university in the West. The archiving system allows in-class students web access to complete video recordings of the actual classroom lectures, and sometimes of lecture notes, shortly after the in-class sessions are completed. The data collection for evaluating the impact of this archiving system was designed through focus groups, and consequently, obtained using a customized web survey. Survey questions targeted areas of potential impact, such as changes in attitudes and behaviors (such as study habits), changes in the dynamics of professor-student relationship, and the overall student performance enhancement. The results indicate that the presence of the archived video lectures and lecture notes adds significant value to the learning process with notable improvements in the perceived student performance and overall experience in the class.

Laryngocele is a rare pathology, but because of their clinical evolution and the symptoms they generate, they should always be considered as a differential diagnosis when investigating neck masses. A laryngocele is basically a herniation of the mucosa of the laryngeal ventricle (Morgagni's ventricle) arising usually from the saccular region. This herniation may remain confined to the larynx - in which case the laryngocele is internal- or expand through the thyro-hyoid membrane into the structures of the neck - thus being called an external laryngocele. Usually the laryngocele has both an internal and external component thus being a mixed laryngocele. Diagnosis of laryngoceles still relies heavily on clinical signs such as tympanism, easily depressible neck mass, indirect laryngoscopy, but is now simplified by imagistic investigations (ultrasound, CT and MRI). However, the treatment of this condition is exclusively surgical and consists of total excision of the laryngocele, as well as proper identification of the point of origin from the saccule and also the final suture of the breach in order to prevent recurrence. Investigation of possible causes of obstruction of the laryngeal ventricle should always be performed (because of the possibility of an underlying malignancy) as well as a follow-up protocol of the patient, given the risk of relapse. We present a recently diagnosed case of a 32 year old man with mixed laryngocele, which we have operated in our clinic.

Due to the advantages offered by agglomerations, human activities have always concentrated, and cities have become multifunctional places: living places, places where goods and services are produced, culture and socialisation places. Nowadays however, the negative effects produced by agglomerations often get to overbalance the positive effects and to repel people and activities. Agglomerations often become impersonal and unfamiliar. They are no longer a “lived space” and people can hardly wait to “evade” at least during the weekend. Among the development factors for which a city should be attractive, Qualified Workforce (QwF) has become the main one, due to the knowledge society we live in. In the Western societies, the QwF has met its basic, material needs, also aiming to meet the others that are linked to the Quality of Life (QoL) (safety, health, mobility, leisure, etc.). That is why the attractiveness for the development factors is more and more linked to the QoL that a city offers, the bicycle being able to bring a large number of answers in this direction. By means of this study, we will try to show the influence that the bicycle has on the urban attractiveness factors. We will find out that the bicycle influences them all and, moreover, without producing any drawbacks in other domains. It exercises however the most powerful effects on two of the most important soft factors of attractiveness, namely QoL and image. By noting the increasing importance of the soft factors in relation to the hard factors, we will be able to sustain the opportunity of investing in facilities for bicycle. Moreover, we will show that a city which aims to remain competitive on the global market of the development factors has no more choices and has to become bicycle-friendly.

Los trastornos neurosensoriales del nervio alveolar inferior (IAN) o el nervio lingual (LN) se reportan comúnmente en casos del tercer molar inferior impactado. Los casos están documentados usualmente mediante estudios imagenológicos. Pruebas de disección de la anatomía detallada en estos casos son raras, sino inexistentes. Se informa aquí sobre un estudio de disección en un caso de un tercer molar inferior impactado (ángulo bucal), en un cadáver de un hombre adulto, 68 años de edad. Más allá de las “clásicas” relaciones del diente impactado con el IAN y el LN, también han sido encontradas estrechas relaciones con las ramas de LN, el ganglio de debajo de la mandíbula, el nervio milohioideo (MN) y la anastomosis del LN y MN. Estos detalles anatómicos deben considerarse también cuando tales casos están documentados en pacientes antes de procedimientos quirúrgicos. Los efectos de los daños del ganglio de debajo de la mandíbula deben ser analizados más. Neurosensory disturbances of the inferior alveolar nerve (IAN), or the lingual nerve (LN), are commonly reported in cases of third mandibular molar impaction. Cases are usually documented by use of imagistic methods. Dissection proofs of the detailed anatomy in such cases are rare, if not absent. It is reported here a dissection study in a case of an impacted (bucco-angular) third mandibular molar, in an adult male cadaver, 68 years old. Beyond the “classical” relations of the impacted tooth with the IAN and the LN, close relations were also found with the LN branches, submandibular ganglion, mylohyoid nerve (MN), and the anastomosis of the LN and the MN. These anatomical details should be also considered when such cases are documented in patients before surgical procedures. Effects of the submandibular ganglion damage should be further explored.

In this work, cuticular waxes from flag leaf blades and peduncles of Triticum aestivum cv. Bethlehem were investigated in search for novel wax compounds. Seven wax compound classes were detected that had previously not been reported, and their structures were elucidated using gas chromatography-mass spectrometry of various derivatives. Six of the classes were identified as series of homologs differing by two methylene units, while the seventh was a homologous series with homologs with single methylene unit differences. In the waxes of flag leaf blades, secondary alcohols (predominantly C27 and C33), primary/secondary diols (predominantly C28) and esters of primary/secondary diols (predominantly C50, combining C28 diol with C22 acid) were found, all sharing similar secondary hydroxyl group positions at and around C-12 or ω-12. 7- and 8-hydroxy-2-alkanol esters (predominantly C35), 7- and 8-oxo-2-alkanol esters (predominantly C35), and 4-alkylbutan-4-olides (predominantly C28) were found both in flag leaf and peduncle wax mixtures. Finally, a series of even- and odd-numbered alkane homologs was identified in both leaf and peduncle waxes, with an internal methyl branch preferentially on C-11 and C-13 of homologs with even total carbon number and on C-12 of odd-numbered homologs. Biosynthetic pathways are suggested for all compounds, based on common structural features and matching chain length profiles with other wheat wax compound classes.

The Regional policy of the EU is pursuing the harmonious development of the European territory; this is a necessary condition for the creation of an environment that is favourable to the convergence of the Union’s policies. But, for these policies to converge, it is necessary that there are common objectives and these can arise only from the existence of common needs. It is obvious that a very different level of development leads to different needs for people and territories and therefore, to the pursuit of different objectives. The introduction of the territorial cohesion as an objective of the European Union through the Treaty of Lisbon has concluded many years of debate over the essence and future of the EU. But is this a prerequisite for the sustainable development of the EU regions? To answer this question, in this paper we will try to show the importance of the territorial cohesion in the EU. In order to do this, we will place the evolution of this concept in parallel with that of development and also with the process of enlargement and of deepening of the EU. We will thus try to determine the influence that territorial cohesion has on regions and on the European construction so that in the end we should be able to explain the effects that it has on their sustainable development.

The mycoestrogen zearalenone (ZEN), as well as its reduced metabolites, which belong to the endocrine disruptor bio-molecule family, are substrates for various enzymes involved in steroid metabolism. In addition to its reduction by the steroid dehydrogenase pathway, ZEN also interacts with hepatic detoxification enzymes, which convert it into hydroxylated metabolites (OH-ZEN). Due to their structures to that of estradiol, ZEN and its derived metabolites bind to the estrogen receptors and are involved in endocrinal perturbations and are possibly associated with estrogen-dependent cancers. The primary aim of this present study was to identify the enzymatic cytochrome P450 isoforms responsible for the formation of the most abundant OH-ZEN. We thus studied its in vitro formation using hepatic microsomes in a range of animal model systems including man. OH-ZEN was also recovered in liver and urine of rats treated orally with ZEN. Finally we compared the activity of ZEN and its active metabolites (α-ZAL and OH-ZEN) on estrogen receptors using HeLa ER-α and ER-β reporter cell lines as reporters. OH-ZEN estrogenic activities were revealed to be limited and not as significant as those of ZEN or α-ZAL.

Elena P Ivanova1, Natasa Mitik-Dineva1, Radu C Mocanasu1, Sarah Murphy1, James Wang2, Grant van Riessen3, Russell J Crawford11Faculty Life and Social Sciences; 2IRIS, Swinburne University of Technology, Hawthorn, Victoria, Australia; 3Centre for Materials and Surface Science, La Trobe University, Melbourne, Victoria, AustraliaAbstract: This study reports the adhesion behavior of two bacterial species, Vibrio fischeri and Escherichia coli, to the photoresistant poly(tert-butyl methacrylate) (P(tBMA)) polymer surface. The data has demonstrated that ultraviolet irradiation of P(tBMA) was able to provide control over bacterial adhesion tendencies. Following photolithography, several of the surface characteristics of P(tBMA) were found to be altered. Atomic force microscopy analysis indicated that photolithographically modified P(tBMA) (henceforth termed ‘modified polymer’) appeared as a ‘nanosmooth’ surface with an average surface roughness of 1.6 nm. Although confocal laser scanning microscopy and scanning electron microscopy analysis clearly demonstrated that V. fischeri and E. coli presented largely different patterns of attachment in order to adhere to the same surfaces, both species exhibited a greater adhesion propensity towards the ‘nanosmooth’ surface. The adhesion of both species to the modified polymer surface appeared to be facilitated by an elevated production of extracellular polymeric substances when in contact with the substrate.Keywords: poly(tert-butylmethacrylate) polymeric surfaces, surface nanotopography, bacterial attachment, extracellular polymeric substances

The increase of energy costs underlines the need to use more efficient drive systems. One of the best solutions to reduce energy costs is the use of variable speed drives. They can easily match motor torque and speed to the load, saving energy when load requirements are reduced. In almost all the cases in a variable speed drive system the motor is fed by a variable frequency electronics power converter. In the last years a tendency of integrating the motor and the frequency converter into a single unit could be observed. A prototype of such a compact variable drive system with a synchronous variable reluctance motor will be presented in this paper.

The original version of this Article contained an error in the spelling of the authors J. H. Joly and N. A. Graham, which were incorrectly given as J. Jolly and N. Graham. Additionally, the affiliation of both authors with 'Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089' and N. A. Graham with 'Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089' was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.

Although numerous therapeutic strategies have attempted to target aerobic glycolysis to inhibit tumor progression, these approaches have not resulted in effective clinical outcomes. Murine squamous cell carcinoma (SCC) can be initiated by hair follicle stem cells (HFSCs). HFSCs utilize aerobic glycolysis, and the activity of lactate dehydrogenase (Ldh) is essential for HFSC activation. We sought to determine whether Ldh activity in SCC is critical for tumorigenesis or simply a marker of the cell type of origin. Genetic abrogation or induction of Ldh activity in HFSC-mediated tumorigenesis shows no effect on tumorigenesis as measured by number, time to formation, proliferation, volume, epithelial to mesenchymal transition, gene expression, or immune response. Ldha-null tumors show dramatically reduced levels of glycolytic metabolites by metabolomics, and significantly reduced glucose uptake by FDG-PET live animal imaging. These results suggest that squamous cancer cells of origin do not require increased glycolytic activity to generate cancers.

The present study examines the impact of a novel online video lecture archiving system on in-class students enrolled in traditional math courses at a mid-sized, primarily undergraduate, university in the West. The archiving system allows in-class students web access to complete video recordings of the actual classroom lectures, and sometimes of lecture notes, shortly after the in-class sessions are completed. The data collection for evaluating the impact of this archiving system was designed through focus groups, and consequently, obtained using a customized web survey. Survey questions targeted areas of potential impact such as: changes in attitudes and behaviors (such as study habits), changes in the dynamics of professor-student relationship, and the overall student performance enhancement. The results indicate that the presence of the archived video lectures and lecture notes adds significant value to the learning process with notable improvements in the perceived student performance and overall experience in the class. (Contains 1 table and 1 figure.)

In the 18th-19th centuries, Roşia-Montană, a village in the Carpathian Mountains of Transylvania (Apuseni), Romania, has been privy to a period of prosperity due to the gold ore existing in the area, but also a period of social and cultural bloom due to the autonomy awarded by the government in Vienna (Transylvania was at the time a province in the Habsburg empire). The community of this village structured around some common goods owing to the harsh environment of mountain living conditions, as well as to the risks inherent to the mining activity. Communism and the following transition towards the market economy reduced the autonomy and transferred properties to the State and subsequently to multinational companies. This had a significant impact on said goods. All these changes then determined the inhabitants to structure around a new “common”.In order to highlight the positive influence of commons on the development, this article performs a historic analysis of the four cornerstone periods of Roşia-Montană. Each of these has witnessed a specific property regimen and specific freedoms of action. Therefore, for each stage we aimed to highlight the degree of co-activity in the life of the people, their capacity to convert the gold ore into real freedom and the satisfaction of their varied needs. This is how we were able to conclude that there is an ongoing connection between commons and development.

In the 18th-19th centuries, Roşia-Montană, a village in the Carpathian Mountains of Transylvania (Apuseni), Romania, has been privy to a period of prosperity due to the gold ore existing in the area, but also a period of social and cultural bloom due to the autonomy awarded by the government in Vienna (Transylvania was at the time a province in the Habsburg empire). The community of this village structured around some common goods owing to the harsh environment of mountain living conditions, as well as to the risks inherent to the mining activity. Communism and the following transition towards the market economy reduced the autonomy and transferred properties to the State and subsequently to multinational companies. This had a significant impact on said goods. All these changes then determined the inhabitants to structure around a new “common”.In order to highlight the positive influence of commons on the development, this article performs a historic analysis of the four cornerstone periods of Roşia-Montană. Each of these has witnessed a specific property regimen and specific freedoms of action. Therefore, for each stage we aimed to highlight the degree of co-activity in the life of the people, their capacity to convert the gold ore into real freedom and the satisfaction of their varied needs. This is how we were able to conclude that there is an ongoing connection between commons and development.