Online audiovisual resources for learning the disinfection protocol for dental impressions: A critical analysis.

STATEMENT OF PROBLEM: Mainly because of poor training, substandard impression disinfection practices have been reported worldwide. PURPOSE: The purpose of this cross-sectional study was to assess the extension, usefulness, and reliability of contents on this topic available on the main video websites for self-training. MATERIAL AND METHODS: An analysis of the YouTube, Vimeo, and Dailymotion websites was undertaken in February 2018. The exclusion criteria were animal procedures, non-English language videos, advertisements, videos exclusively redirecting to websites, soundless videos, duplicated videos, and videos reporting on a research project. Information extension was assessed in 6 nonmutually exclusive dimensions, and usefulness was evaluated by using a 10-item scale. Reliability was assessed on a reliable or nonreliable basis. Statistical analyses were undertaken by using the Mann-Whitney and Fisher exact tests. RESULTS: Of 386 identified videos, only 22 met the selection criteria, mostly published by health-care professionals (n=8; 36.4%). Most videos had less than 3000 views. Median usefulness score: 3 (IR: 3-3; range: 0-6). No video included all 7 topics considered in the index (median 3; IR: 2.25-3; range: 0-4). Just 5 clips (22.7%) described a procedure according to the American Dental Association and Center for Disease Control (ADA and CDC) guidelines. CONCLUSIONS: Audiovisual online resources on dental impression disinfection includes incomplete information with limited usefulness and reliability. The number of views was not related to quality, and therefore, many viewers may be obtaining knowledge from substandard material.

Diffuse Cosmic Rays Shining in the Galactic Center: A Novel Interpretation of H.E.S.S. and Fermi-LAT γ-Ray Data.

We present a novel interpretation of the γ-ray diffuse emission measured by Fermi-LAT and H.E.S.S. in the Galactic center (GC) region and the Galactic ridge (GR). In the first part we perform a data-driven analysis based on PASS8 Fermi-LAT data: We extend down to a few GeV the spectra measured by H.E.S.S. and infer the primary cosmic-ray (CR) radial distribution between 0.1 and 3 TeV. In the second part we adopt a CR transport model based on a position-dependent diffusion coefficient. Such behavior reproduces the radial dependence of the CR spectral index recently inferred from the Fermi-LAT observations. We find that the bulk of the GR emission can be naturally explained by the interaction of the diffuse steady-state Galactic CR sea with the gas present in the central molecular zone. Although we confirm the presence of a residual radial-dependent emission associated with a central source, the relevance of the large-scale diffuse component prevents to claim a solid evidence of GC pevatrons.

Neumopericardio en paciente con rotura traqueal tras politraumatismo por accidente de tráfico / Pneumopericardium in a patient with tracheal rupture after multiple injuries from a traffic accident

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Impact of hexavalent chromium on mammalian cell bioenergetics: phenotypic changes, molecular basis and potential relevance to chromate-induced lung cancer.

Occupational exposure to hexavalent chromium [Cr(VI)] has been firmly associated with the development of several pathologies, notably lung cancer. According to the current paradigm, the evolution of normal cells to a neoplastic state is accompanied by extensive metabolic reprogramming, namely at the level of energy-transducing processes. Thus, a complete understanding of the molecular basis of Cr(VI)-induced lung cancer must encompass the elucidation of the impact of Cr(VI) on metabolism. Research in this area is still in its infancy. Nonetheless, Cr(VI)-induced metabolic phenotypes are beginning to emerge. Specifically, it is now well documented that Cr(VI) exposure inhibits respiration and negatively affects the cellular energy status. Furthermore, preliminary results suggest that it also upregulates glucose uptake and lactic acid fermentation. From a mechanistic point of view, there is evidence that Cr(VI) exposure can interfere with energy transducing pathways at different levels, namely gene expression, intracellular protein levels and/or protein function. Loss of thiol redox control likely plays a key role in these processes. The transcriptional networks that control energy transduction can likewise be affected. Data also suggest that Cr(VI) exposure might compromise energy transducing processes through changes in the intracellular pools of their substrates. This article reviews, for the first time, the information available on Cr(VI) impact on mammalian cell bioenergetics. It aims to provide a framework for the understanding of the role played by bioenergetics in Cr(VI)-induced carcinogenesis and is also intended as a guide for future research efforts in this area.

Central obesity and altered peripheral adipose tissue gene expression characterize the NAFLD patient with insulin resistance: Role of nutrition and insulin challenge.

OBJECTIVE: Insulin resistance (IR) and white adipose tissue (WAT) dysfunction frequently are associated with nonalcoholic fatty liver disease (NAFLD); however, the pathogenic mechanisms contributing to their clustering are not well defined. The aim of this study was to define some nutritional, anthropometric, metabolic, and genetic mechanisms contributing to their clustering. METHODS: Forty-five (20 men, 25 women) patients (age 45.7 ± 11.1 y) with recent diagnosis of NAFLD were grouped according to IR state. Energy balance was assessed using a food questionnaire and indirect calorimetry, and body composition with anthropometry and dual-energy x-ray absorptiometry. Biochemical and hormonal parameters combined with adipose tissue gene expression were determined. Microarray analysis of gene expression was performed in a subset of WAT samples from IR patients (n = 9), in the fasted state, after specific test meals (monounsaturated fatty acid [MUFA], saturated fat [SAT], and carbohydrate-rich) and after being challenged with insulin. RESULTS: IR patients exhibited higher trunk fat to leg fat ratio (P < 0.05) and had a higher ratio of SAT/MUFA fat intake (P < 0.05) than insulin-sensitive (IS) individuals. Deposition of fat in the trunk but not in the leg was directly related to liver enzyme levels (P < 0.05). IR patients also had lower adiponectin serum levels and leptin (LEP) mRNA expression in WAT compared with IS patients (P < 0.01 and P < 0.05, respectively). Microarray analysis after insulin challenge confirmed that insulin treatment induces the expression of PPARG gene and LEP and decreases GCGR gene (P < 0.05 for all) in WAT. No changes in these genes were observed in the postprandial state induced after the acute effect of specific diets. CONCLUSIONS: Patients exhibiting NAFLD and IR had preferential central fat deposition directly related to their serum alanine aminotransferase levels. These patients showed peripheral adipose tissue dysfunction and exhibited inappropriately low LEP biosynthesis that could be partially restored after anabolic conditions induced by insulin signaling.

Nutritional intake according to injury extent in ulcerative colitis patients.

BACKGROUND: Ulcerative colitis (UC) is often associated with nutritional deficiency, which appears to contribute to the progression of UC severity. The present study aimed to evaluate nutritional status and dietary intake in UC remission patients. METHODS: The present study comprised a cross-sectional study in which variables such as extent of disease (distal colitis, left-sided colitis, pancolitis), remission period, sex and age were recorded. Extent of disease was assessed by the results of a colonoscopy and dietary intake was evaluated by using 3-day, 24-h recalls. A Kruskall-Wallis test was used to compare the intake of macro- and micronutrients among the three study groups. The analysis was complemented by the Mann-Whitney test. A logistic regression analysis was performed to identify predictive factors of extent of disease (pancolitis versus left-sided colitis versus distal colitis). RESULTS: The median (range) age of the 59 patients was 49.0 (37.0-63.0) years and 53.3% were female. Twenty-six (44.1%) patients had distal colitis, 11 (18.6%) patients had left-sided colitis and 22 (37.3%) patients had pancolitis. A high probability of an inadequate intake of fibre (100%), fat soluble vitamins (>40% for vitamin A and >95% for vitamin E), vitamin C (>34%), calcium (>90%) and magnesium (>50%) was identified in the study group. Vitamin D intake (odds ratio = 0.60; 95% confidence interval = 0.39-0.94; P < 0.05) was significantly associated with increased intestinal damage. CONCLUSIONS: A large number of individuals showed an inadequate intake of nutrients. In addition, the consumption of vitamin D was significantly associated with extent of disease.

Molecular and cellular mechanisms of hexavalent chromium-induced lung cancer: an updated perspective.

For over a century, chromium (Cr) has found widespread industrial and commercial use, namely as a pigment, in the production of stainless steel and in chrome plating. The adverse health effects to the skin and respiratory tract of prolonged exposure to Cr have been known or suspected for a long time, but it was much more recently that the toxicity of this element was unequivocally attributed to its hexavalent state. Based on the combined results of extensive epidemiological studies, animal carcinogenicity studies and several types of other relevant data, authoritative regulatory agencies have found sufficient evidence to classify hexavalent chromium [Cr(VI)] compounds as encountered in the chromate production, chromate pigment production and chromium plating industries as carcinogenic to humans. Crucial for the development of novel strategies to prevent, detect and/or treat Cr(VI)-induced cancers is a detailed knowledge of the molecular and cellular mechanisms underlying these pathologies. Unfortunately, in spite of a considerable research effort, crucial facets of these mechanisms remain essentially unknown. This review is intended to provide a concise, integrated and critical perspective of the current state of knowledge concerning multiple aspects of Cr(VI) carcinogenesis. It will present recent theories of Cr(VI)-induced carcinogenesis and will include aspects not traditionally covered in other reviews, such as the possible involvement of the energy metabolism in this process. A brief discussion on the models that have been used in the studies of Cr(VI)-induced carcinogenicity will also be included, due to the impact of this parameter on the relevance of the results obtained.

Conserved features of cancer cells define their sensitivity to HAMLET-induced death; c-Myc and glycolysis.

HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here, we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small-hairpin RNA (shRNA) inhibition, proteomic and metabolomic technology, we identified the c-Myc oncogene as one essential determinant of HAMLET sensitivity. Increased c-Myc expression levels promoted sensitivity to HAMLET and shRNA knockdown of c-Myc suppressed the lethal response, suggesting that oncogenic transformation with c-Myc creates a HAMLET-sensitive phenotype. Furthermore, HAMLET sensitivity was modified by the glycolytic state of tumor cells. Glucose deprivation sensitized tumor cells to HAMLET-induced cell death and in the shRNA screen, hexokinase 1 (HK1), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 and hypoxia-inducible factor 1α modified HAMLET sensitivity. HK1 was shown to bind HAMLET in a protein array containing ∼8000 targets, and HK activity decreased within 15 min of HAMLET treatment, before morphological signs of tumor cell death. In parallel, HAMLET triggered rapid metabolic paralysis in carcinoma cells. Tumor cells were also shown to contain large amounts of oleic acid and its derivatives already after 15 min. The results identify HAMLET as a novel anti-cancer agent that kills tumor cells by exploiting unifying features of cancer cells such as oncogene addiction or the Warburg effect.

Human bronchial epithelial cells malignantly transformed by hexavalent chromium exhibit an aneuploid phenotype but no microsatellite instability.

Hexavalent chromium [Cr(VI)] is a well-recognized human lung carcinogen. In order to gain further insight into Cr(VI)-induced carcinogenesis, we have established an adequate in vitro cellular model for the study of this process. To this end, BEAS-2B cells were used. Chronic exposure of cells to 1 microM Cr(VI) induced changes in the cells' ploidy and a decrease in cloning efficiency, although cultures continued to progress to confluence. After prolonged exposure (12 passages), the culture became heterogeneous, exhibiting areas where apparently normal epithelial cells and morphologically altered cells coexisted. Subsequent culture at a very low density strongly accentuated the Cr(VI)-induced changes in morphology and pattern of growth. Three individual colonies were then ring-cloned and expanded into three subclonal aneuploid cell lines. These subclonal cell lines showed changes in growth pattern and morphology, as well as a karyotype drift concomitant with the overexpression of genes commonly involved in malignant transformation (c-MYC, EGFR, HIF-1alpha and LDH-A). Moreover, when one of these cell lines (RenG2) was injected into nude mice, it showed the ability to induce tumors. This cell line revealed no microsatellite instability (MSI), which points to the expression of a functional MLH1 protein and an active mismatch repair (MMR) system. Therefore, the progression to malignancy of the BEAS-2B cells involved Cr(VI)-induced transformants that retained the ability to repair DNA damage, suggesting that genotoxicity underlies the ongoing carcinogenic process.

Euglycemic hyperinsulinemic clamp

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Insulin is the principal hormone of glucose metabolic regulation. Reduced glucose responses to insulin constitute an underlying feature of type 2 diabetes. In addition, insulin resistance is a common condition related with the metabolic syndrome and strongly associated with an increased risk of cardiovascular disease. The importance of the insulin-resistant phenotype for the assessment of cardiovascular risk and response to intervention is increasingly being recognized. Therefore, there is a need for an accurate and reproducible method for measuring insulin resistance in vivo. The euglycemic hyperinsulinemic clamp (EHC) is currently the gold standard method available for the determination of whole glucose uptake in response to insulin, from which several derived indices of insulin sensitivity are obtained. The clamp technique is both expensive and complex to undertake and has prompted the use of surrogate methods, notably the insulin tolerance test and frequently sampled intravenous glucose tolerance test. Indices may be derived from these methods and correlate well with those derived from clamp studies. However, important limitations of these procedures are that not only does insulin sensitivity change in pathological situations, but also in normal physiology. Variations also occur in time–depending on the physiological state of the individual or following diurnal rhythms. In conclusion, the quantitative assessment of insulin sensitivity with EHC is not used for routine clinical purposes, but the emerging importance of insulin resistance has led to its wider application to research studies that have examined its pathogenesis, etiology and consequences (AU)

Effects of overexpression of the liver subunit of 6-phosphofructo-1-kinase on the metabolism of a cultured mammalian cell line.

Overexpression of the liver subunit of 6-phosphofructo-1-kinase in Chinese hamster ovary K1 cells was shown to increase the steady-state level of the enzyme's product, fructose 1, 6-bisphosphate, and to produce a small but significant decrease in the concentration of fructose 2,6-bisphosphate, which is an allosteric activator of the enzyme. However, overexpression of the enzyme had no effect on glycolytic flux under a variety of different substrate conditions. This latter observation is consistent with similar studies in fungi and in potato tubers which indicate that 6-phosphofructo-1-kinase has very little control over flux in glycolysis.

Studies of Diastereoselectivity in Diels-Alder Reactions of Enantiopure (SS)-2-(p-Tolylsulfinyl)-1,4-naphthoquinone and Chiral Racemic Acyclic Dienes.

Enantiopure sulfinylnaphthoquinone (+)-5 reacted with racemic acyclic dienes 1a-f bearing a stereogenic allylic center, through a tandem cycloaddition/pyrolytic sulfoxide elimination, to afford optically enriched compounds 8a-f and 9a-f with good like/unlike selectivities (ca. 75:25) and good enantiomeric excesses (68-82%), arising from the partial kinetic resolution of the racemic dienes. The opposite diastereoselection (8g-i: 9g-i, up to 5:95) was observed in reactions with dienes 1g-i, having an additional methyl group at C-3, the enantiomeric purities being moderate (14-25%). Steric effects and torsional interactions in the corresponding approaches account for the observed diastereoselectivities.

Enantioselective Diels-Alder approach to C-3-oxygenated angucyclinones from (SS)-2-(p-tolysulfinyl)-1,4-naphthoquinone.

Chiral racemic vinylcyclohexenes 2, bearing oxygenated substituents and/or a methyl group at the C-5 position of the cyclohexene ring, were submitted to Diels-Alder reactions with enantiomerically pure (SS)-(2-p-tolylsulfinyl)-1,4-naphthoquinone [(+)-1]. The domino cycloaddition/pyrolytic sulfoxide elimination process led to the formation of enantiomerically enriched angularly tetracyclic quinones anti-6 and syn-7, which were obtained from the kinetic resolution of the racemic diene. In all cases, (SS)-(2-p-tolylsulfinyl)-1,4-naphthoquinone reacted from the less hindered face of the more reactive s-cis conformation, to form products in good enantiomeric excesses. Steric effects and torsional interactions in the corresponding approaches account for the observed pi-facial diastereoselectivities at both partners. The usefulness of this methodology is illustrated with the four-step totally asymmetric synthesis of the C-3-oxygenated angucyclinone derivative (-)-8-deoxytetrangomycin 10 in 26% overall yield and with 50% enantiomeric purity.

GDNF and RET-gene expression in anterior pituitary-cell types.

Glial cell line-derived neurotrophic factor (GDNF) is expressed in many neuronal and non-neuronal tissues during development as well as in adult animals. GDNF signaling is mediated through a two-component system consisting of the so called GDNF receptor-alfa (GFRalpha1) which binds to GDNF. Thereafter this complex binds to and activates the tyrosine kinase receptor RET. In this work, for the first time, we have characterized the expression of both GDNF and RET in the anterior pituitary. First of all, RT-PCR analysis, Western blot and immunohistochemistry of the whole anterior pituitary showed that GDNF, GFRalpha1 and RET are expressed in this gland. Following double-immunofluorescence of consecutive sections we found GDNF immunoreactivity in most cell types, and it was most abundant in corticotrophs (55%), LH (59%) and FSH-producing cells (81%). In contrast, while the majority of somatotrophs (87%) were stained for RET, no positive immunostaining could be detected in other cell types. Taken together, this data indicate that gonadotrophs and corticotrophs are the main source of GDNF synthesized in the anterior pituitary and that the somatotrophs appears to be their target cell. This study provides direct morphological evidences that GDNF may well be acting in a paracrine-like fashion in the regulation of somatotroph cell growth and/or cell function.

Diels-alder reactions with 2-(Arylsulfinyl)-1,4-benzoquinones: effect of aryl substitution on reactivity, chemoselectivity, and pi-facial diastereoselectivity

Diels-Alder reactions of (SS)-2-(2'-methoxynaphthylsulfinyl)-1, 4-benzoquinone (1b), 2-(p-methoxyphenylsulfinyl)-1,4-benzoquinone (1c), and 2-(p-nitrophenylsulfinyl)-1,4-benzoquinone (1d) with cyclopentadiene are reported. These cycloadditions allowed the highly chemo- and stereoselective formation of both diastereoisomeric endo-adducts resulting from reaction on the unsubstituted double bond C(5)-C(6) of quinones working under thermal and Eu(fod)(3)- or BF(3).OEt(2)-catalyzed conditions. The synthesis of endo-adduct [4aS,5S,8R,8aR,SS]-9d resulting from cycloaddition on the substituted C(2)-C(3) double bond was achieved in a chemo- and diastereoselective way from quinone 1d in the presence of ZnBr(2). The reactivity and selectivity of the process proved to be dependent on the electron density of the arylsulfinyl group.

Comparison between human and artificial neural network detection of Laplacian-derived electroencephalographic activity related to unilateral voluntary movements.

A back-propagation artificial neural network (ANN) was tested to verify its capacity to select different classes of single trials (STs) based on the spatial information content of electroencephalographic activity related to voluntary unilateral finger movements. The rationale was that ipsilateral and contralateral primary sensorimotor cortex can be involved in a nonstationary way in the control of unilateral voluntary movements. The movement-related potentials were surface Laplacian-transformed (SL) to reduce head volume conductor effects and to model the response of the primary sensorimotor cortex. The ANN sampled the SL from four or two central channels overlying the primary motor area of both sides in the period of 80 ms preceding the electromyographic response onset in the active muscle. The performance of the ANN was evaluated statistically by calculating the percentage value of agreement between the STs classified by the ANN and those of two investigators (used as a reference). The results showed that both investigator and ANN were capable of selecting STs with the SL maximum in the central area contralateral to the movement (contralateral STs, about 25%), STs with considerable SL values also in the ipsilateral central area (bilateral STs, about 50%), and STs with neither the contralateral nor bilateral pattern ("spatially incoherent" single trials; about 25%). The maximum agreement (64-84%) between the ANN and the investigator was obtained when the ANN used four spatial inputs (P < 0.0000001). Importantly, the common means of all single trials showed a weak or absent ipsilateral response. These results may suggest that a back-propagation ANN could select EEG single trials showing stationary and nonstationary responses of the primary sensorimotor cortex, based on the same spatial criteria as the experimenter.

[Cervix uteri lesions and human papiloma virus infection (HPV): detection and characterization of DNA/HPV using PCR (polymerase chain reaction]. / Lesões do colo uterino e infecção pelo vírus do papiloma humano (HPV) detecção e tipificação do ADN/HPV por PCR (reacção de amplificação enzimática).

The prevalence of human papillomavirus (HPV) genotypes was estimated by the polymerase chain reaction (PCR), in archival paraffin was embedded tissues. The case group consisted of 84 women aged 21-67 years (mean, 40 years) who were referred to the Department of Gynaecology (Oncology Centre, Coimbra) with citopathologically abnormal smears. This group was selected from a population of women who had undergone a screening programme (1990/94) in Central Region of Portugal. All these patients (n = 84) had a colposcopic directed cervical biopsy. HPV detection and typing was performed by the PCR method in the Department of Virology (National Health Care Institute, Lisbon). The prevalence of DNA/HPV found, concerning all epithelial cervical lesions studied and classified as squamous intra-epithelial lesions (SIL) and cervical cancer was 97.8%. On the basis of the data presented in this study, it was estimated that there was a statistically significant prevalence of low risk HPV types (HPV 6/11) in low grade SIL, 83.3%, and a statistically significant prevalence of high risk HPV types (HPV 16,18,31,33,51) in high grade SIL, 58.4%, as well as cervical cancer lesions in 100%. We conclude that there was a statistically significant difference between women with low and high grade SIL for HPV infection, with low and high risk HPV types, respectively. The risk factors for cervical cancer investigated (age at first sexual intercourse, multiple sexual partners, parity, use of oral contraceptives) were not associated to statistically significant differences concerning low grade SIL and high grade SIL. The clinical and therapeutic procedures were evaluated for the same five years (1990/94). It may be concluded that there would be no significant difference in clinical procedure for high grade lesions and cervical cancer, in which the treatment had been frequently radical (cone biopsies, simple or radical hysterectomy) and in which the HPV infection persisted frequently and was associated to high risk types (HPV 16 in 50% of these cases). On the other hand, it may be concluded that HPV detection in cervical biopsies, especially for low grade SIL lesions, which were evaluated in this study with a more conservative procedure (clinical evaluation only, punch biopsies, loop diathermy, CO2 laser vaporisation, cone biopsies), could identify women with high risk HPV types who might be at risk of developing dysplasia and cervical cancer.