Journal articles on the topic 'LC-DS/MS'

AbstractWe aimed to configure impaired/altered metabolomic profiles of pregnant women carrying Down syndrome (DS) fetuses. The study involved 21 and 32 pregnant women with DS and euploid fetuses, respectively, as determined by prenatal screening and diagnosis as part of an antenatal care program. Metabolomic analyses were carried out using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-qTOF-MS) methods. A total of 95 metabolites were identified. GC-MS analysis indicated that levels of 2-hydroxybutyric acid, benzoic acid, nonanoic acid, 3-hydroxybutyric acid, and 2-ketoisocaproic acid were increased in the DS group, where beta-alanine, threonic acid, oxalic acid, alpha-tocopherol, uracil, 2-piperidone, and creatinine were decreased. However, LC-qTOF-MS analysis showed that lipid-related metabolites were decreased in women carrying DS fetuses, whereas creatine, N4-phosphoagmatine, citrate, 2,5-dioxopentanoate, 2-furoate, pyruvate, and fructose levels were increased. Pathway analysis was also performed using metabolites whose levels were significantly altered (p<0.05) between the groups, and the findings indicated that the biosynthesis pathways of aminoacyl-tRNA and “valine-leucine-isoleucine”, and metabolism pathways of “glycine-serine-threonine”, nitrogen, “alanine-aspartate-glutamate”, propanoate, glycerophospholipid, cysteine, methionine, and phenylalanine were significantly altered. Our findings indicate a special type of metabolic status/syndrome in pregnant women with Down syndrome fetuses. It could be speculated that altered metabolic status might influence both gametogenesis and embryogenesis. Down syndrome is a complex genetic disorder that is important to detect prenatally, but may also be prevented by taking necessary precautions prior to pregnancy.

The objective of this study is to clone and charecterize the expression of dammarenediol synthase gene and then to determine the relationship between the expression of dammarenediol synthase gene that is involved in the ginsenoside biosynthetic pathway and the ginsenoside content. A cDNA phage library was constructed from a five-year-old ginseng root. The cDNA library was screened for the dammarenediol synthase gene by using its specific primers. It was further cloned and expressed in pET-30a vector. The recombinant plasmid pET-30a-DS was expressed in RosettaE. coli. The recombinant DS protein was purified by affinity chromatography. The production of dammarenediol was detected by liquid chromatography-mass spectrometry (LC-MS). Results showed that dammarenediol synthase gene was cloned from the cDNA library and was expressed in RosettaE. coliand the SDS-PAGE analysis showed the presence of purified DS protein. LS-MS showed the activity of DS protein, as the protein content increases the dammarenediol increases. Our results indicate that the recombinant dammarenediol synthase protein could increase the production of dammarenediol and the expression of DS played a vital role in the biosynthesis of ginsenosides inP. ginseng.

AbstractObjectivesMucopolysaccharidosis type I (MPS I) was added to our expanded screening panel in 2015. Since then, 127,869 newborns were screened by measuring α-L-iduronidase (IDUA) enzyme activity with liquid chromatography tandem mass spectrometry (LC-MS/MS). High false positives due to frequent pseudodeficiency alleles prompted us to develop a second-tier test to quantify glycosaminoglycan (GAG) levels in dried blood spot (DBS).MethodsHeparan-sulfate (HS) and dermatan-sulfate (DS) were measured with LC-MS/MS after methanolysis. DBSs were incubated with methanolic-HCl 3 N at 65 °C for 45 min. Chromatographic separation used an amide column with a gradient of acetonitrile and water with 10 mM ammonium acetate in a 9-min run. The method was validated for specificity, linearity, lower limit of quantification (LOQ), accuracy and precision.ResultsIntra- and inter-day coefficients of variation were <15% for both metabolites. Reference values in 40 healthy newborns were: HS mean 1.0 mg/L, 0–3.2; DS mean 1.5 mg/L, 0.5–2.7). The two confirmed newborn MPS I patients had elevated HS (4.9–10.4 mg/L, n.v. <3.2) and DS (7.4–8.8 mg/L, n.v. <2.7). Since its introduction in February 2019, the second-tier test reduced the recall rate from 0.046% to 0.006%. Among 127,869 specimens screened, the incidence was 1:63,935 live births. Both patients started enzyme replacement therapy (ERT) within 15 days of birth and one of them received allogenic hematopoietic stem cell transplantation (HSCT) at ht age of 6 months.ConclusionsGAGs in DBS increased the specificity of newborn screening for MPS I by reducing false-positives due to heterozygosity or pseudodeficiency. Early diagnosis and therapeutical approach has improved the outcome of our patients with MPS I.

Isoprene is a small lipophilic molecule synthesized in plastids and abundantly released into the atmosphere. Isoprene-emitting plants are better protected against abiotic stresses, but the mechanism of action of isoprene is still under debate. In this study, we compared the physiological responses and proteomic profiles of Arabidopsis which express the isoprene synthase (ISPS) gene and emit isoprene with those of non-emitting plants under both drought-stress (DS) and well-watered (WW) conditions. We aimed to investigate whether isoprene-emitting plants displayed a different proteomic profile that is consistent with the metabolic changes already reported. Only ISPS DS plants were able to maintain the same photosynthesis and fresh weight of WW plants. LC–MS/MS-based proteomic analysis revealed changes in protein abundance that were dependent on the capacity for emitting isoprene in addition to those caused by the DS. The majority of the proteins changed in response to the interaction between DS and isoprene emission. These include proteins that are associated with the activation of secondary metabolisms leading to ABA, trehalose, and proline accumulations. Overall, our proteomic data suggest that isoprene exerts its protective mechanism at different levels: under drought stress, isoprene affects the abundance of chloroplast proteins, confirming a strong direct or indirect antioxidant action and also modulates signaling and hormone pathways, especially those controlling ABA synthesis. Unexpectedly, isoprene also alters membrane trafficking.

Background: The mucopolysaccharidoses (MPSs) are a group of rare lysosomal storage disorders characterized by the accumulation of glycosaminoglycans (GAGs) and which eventually cause progressive damage to various tissues and organs. We developed a feasible MPS screening algorithm and established a cross-specialty collaboration platform between medical geneticists and other medical specialists based on at-risk criteria to allow for an earlier confirmative diagnosis of MPS. Methods: Children (<19 years of age) with clinical signs and symptoms compatible with MPS were prospectively enrolled from pediatric clinics between July 2013 and June 2018. Urine samples were collected for a non-specific total GAG analysis using the dimethylmethylene blue (DMB) spectrophotometric method, and the quantitation of three urinary GAGs (dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS)) was performed by liquid chromatography/tandem mass spectrometry (LC-MS/MS). The subjects with elevated urinary GAG levels were recalled for leukocyte enzyme activity assay and genetic testing for confirmation. Results: Among 153 subjects enrolled in this study, 13 had a confirmative diagnosis of MPS (age range, 0.6 to 10.9 years—three with MPS I, four with MPS II, five with MPS IIIB, and one with MPS IVA). The major signs and symptoms with regards to different systems recorded by pediatricians at the time of the decision to test for MPS were the musculoskeletal system (55%), followed by the neurological system (45%) and coarse facial features (39%). For these 13 patients, the median age at the diagnosis of MPS was 2.9 years. The false negative rate of urinary DMB ratio using the dye-based method for these 13 patients was 31%, including one MPS I, two MPS IIIB, and one MPS IVA. However, there were no false negative results with urinary DS, HS and KS using the MS/MS-based method. Conclusions: We established an at-risk population screening program for MPS by measuring urinary GAG fractionation biomarkers using the LC-MS/MS method. The program included medical geneticists and other medical specialists to increase awareness and enable an early diagnosis by detecting MPS at the initial onset of clinical symptoms.

Neuroinflammation plays a critical role in the pathogenesis of most neurological and neurodegenerative diseases and therefore represents a potential therapeutic target. In this regard, accelerating the resolution process in chronic neuroinflammation may be an effective strategy to deal with the cognitive consequences of neuropathology and generalized inflammatory processes. N-acylethanolamine (NAE) derivatives of fatty acids, being highly active lipid mediators, possess pro-resolving activity in inflammatory processes and are promising agents for the suppression of neuroinflammation and its consequences. This paper is devoted to a study of the effects played by dietary supplement (DS), containing a composition of fatty acid-derived NAEs, obtained from squid Berryteuthis magister, on the hippocampal neuroinflammatory and memory processes. By detecting the production of pro-inflammatory cytokines and glial markers, a pronounced anti-inflammatory activity of DS was demonstrated both in vitro and in vivo. DS administration reversed the LPS-induced reduction in hippocampal neurogenesis and memory deterioration. LC-MS analysis revealed an increase in the production of a range of NAEs with well-documented anti-inflammatory activity in response to the administered lipid composition. To conclude, we found that tested DS suppresses the neuroinflammatory response by reducing glial activation, positively regulates neural progenitor proliferation, and attenuates hippocampal-dependent memory impairment.

Most multidrug-resistant tuberculosis (MDR-TB) patients fail to receive a timely diagnosis and treatment. Therefore, we explored the differentially expressed peptides in MDR-TB compared with drug-susceptible tuberculosis (DS-TB) patients using LC-MS/MS and Ingenuity Pathway Analysis (IPA) to analyse the potential significance of these differentially expressed peptides. A total of 301 peptides were differentially expressed between MDR-TB and DS-TB groups. Of these, 24 and 16 peptides exhibited presented high (fold change ≥ 2.0, P < 0.05) and low (fold change ≤ −2.0, P < 0.05) levels in MDR-TB. Significant canonical pathways included the prothrombin activation system, coagulation system, and complement system. In the network of differentially expressed precursor proteins, lipopolysaccharide (LPS) regulates many precursor proteins, including four proteins correlated with organism survival. These four important differentially expressed proteins are prothrombin (F2), complement receptor type 2 (CR2), collagen alpha-2(V) chain (COL5A2), and inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4). After addition of CR2 peptide, IL-6 mRNA expression in THP-1 cells decreased significantly in dose- and time-dependent manners. Cumulatively, our study proposes potential biomarkers for MDR-TB diagnosis and enables a better understanding of the pathogenesis of MDR-TB. The functions of differentially expressed peptides, especially CR2, in MDR-TB require further investigation.

AbstractLGD-4033 (ligandrol) is a selective androgen receptor modulator (SARM), which is prohibited in sports by the World Anti-Doping Agency (WADA) and led to 62 adverse analytical findings (AAFs) in 2019. But not only deliberate doping with LGD-4033 constitutes a problem. In the past years, some AAFs that concerned SARMs can be attributed to contaminated dietary supplements (DS). Thus, the urgency to develop methods to differentiate between inadvertent doping and abuse of SARMs to benefit from the performance-enhancing effect of the compound in sports is growing. To gain a better understanding of the metabolism and excretion patterns of LGD-4033, human micro-dose excretion studies at 1, 10, and 50 µg LGD-4033 were conducted. Collected urine samples were prepared for analysis using enzymatic hydrolysis followed by solid-phase extraction and analyzed via LC-HRMS/MS. Including isomers, a total of 15 phase I metabolites were detected in the urine samples. The LC-HRMS/MS method was validated for qualitative detection of LGD-4033, allowing for a limit of detection (LOD) of 8 pg/mL. The metabolite M1, representing the epimer of LGD-4033, was synthesized and the structure elucidated by NMR spectroscopy. As the M1/LGD-4033 ratio changes over time, the ratio and the approximate LGD-4033 concentration can contribute to estimating the time point of drug intake and dose of LGD-4033 in doping control urine samples, which is particularly relevant in anti-doping result management. Graphical abstract

Background. Naolingsu capsule (NLSC) is a well-known traditional Chinese medicine (TCM) prescription in China. It is widely used to treat neurasthenia, insomnia, cardiovascular and cerebrovascular disease, and other diseases. However, its inalienable chemical groups have not been carried out. Methods. We first established the nontargeted investigation based on fingerprinting coupled with UHPLC-Q/TOF-MS/MS. Second, the quantitative methods based on HPLC-DAD and LC-MS/MS were connected to the synchronous quantitative assurance of eleven and fourteen marker compounds. Finally, the quantitative information was processed with SIMCA-P for differentiating the distinctive bunches of samples to screen the foremost appropriate chemical markers. Results. The similarity of HPLC fingerprints of 24 batches of NLSC samples was 0.645–0.992. In total, 37 flavonoids, 21 organic acids, 22 lignans, 13 saponins, and 20 other compounds were recognized in NLSC by the UHPLC-Q/TOF-MS/MS method. The quantitative determination was approved for linearity, discovery limits, accuracy, repeatability, soundness, and precision. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models accomplished the great classification of the samples from the five enterprises, respectively. Rehmannioside D (RD), methylophiopogonanone A (MPA), 3,6′-disinapoyl sucrose (DS), schisandrin B (SSB), epimedin C (EC), icariin (ICA), and jujuboside B (JB) were considered as the potential chemical markers for NLSC quality control. Conclusion. The experimental results illustrated that the combinative strategy was valuable for quick pharmaceutical quality assessment, which can potentially differentiate the origin, decide the realness, and assess the overall quality of the formulation.

Mucopolysaccharidoses (MPS) and mucolipidosis (ML II/III) are a group of lysosomal storage disorders (LSDs) that occur due to a dysfunction of the lysosomal hydrolases responsible for the catabolism of glycosaminoglycans (GAGs). However, ML is caused by a deficiency of the enzyme uridine-diphosphate N-acetylglucosamine:lysosomal-enzyme-N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase, EC2.7.8.17), which tags lysosomal enzymes with a mannose 6-phosphate (M6P) marker for transport to the lysosome. A timely diagnosis of MPS and ML can lead to appropriate therapeutic options for patients. To improve the accuracy of diagnosis for MPS and ML in a high-risk population, we propose a combination method based on known biomarkers, enzyme activities, and specific GAGs. We measured five lysosomal enzymes (α-L-iduronidase (MPS I), iduronate-2-sulfatase (MPS II), α-N-acetylglucosaminidase (MPS IIIB), N-acetylglucosamine-6-sulfatase (MPS IVA), and N-acetylglucosamine-4-sulfatase (MPS VI)) and five GAGs (two kinds of heparan sulfate (HS), dermatan sulfate (DS), and two kinds of keratan sulfate (KS)) in dried blood samples (DBS) to diagnose suspected MPS patients by five-plex enzyme and simultaneous five GAGs assays. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) for both assays. These combined assays were tested for 43 patients with suspected MPS and 103 normal control subjects. We diagnosed two MPS I, thirteen MPS II, one MPS IIIB, three MPS IVA, two MPS VI, and six ML patients with this combined method, where enzymes, GAGs, and clinical manifestations were compatible. The remaining 16 patients were not diagnosed with MPS or ML. The five-plex enzyme assay successfully identified MPS patients from controls. Patients with MPS I, MPS II, and MPS IIIB had significantly elevated HS and DS levels in DBS. Compared to age-matched controls, patients with ML and MPS had significantly elevated mono-sulfated KS and di-sulfated KS levels. The results indicated that the combination method could distinguish these affected patients with MPS or ML from healthy controls. Overall, this study has shown that this combined method is effective and can be implemented in larger populations, including newborn screening.

The aminocoumarin antibiotic clorobiocin contains a 5-methylpyrrole-2-carboxylic acid unit, attached via an ester bond to the 3-OH group of the deoxysugar moiety. To investigate candidate genes responsible for the formation of this ester bond, a gene inactivation experiment was carried out in the clorobiocin producer Streptomyces roseochromogenes var. oscitans DS 12.976. An in-frame deletion was created in the coding sequence of the gene cloN2. The production of secondary metabolites in the wild-type and in the cloN2 mutant was analysed. The wild-type showed clorobiocin as the main product, whereas the cloN2 mutant accumulated a new aminocoumarin derivative, novclobiocin 104, lacking the pyrrole moiety at the 3-OH of the deoxysugar. In addition, free pyrrole-2-carboxylic acid accumulated in the culture extract of the cloN2 mutant. The structures of the metabolites were confirmed by NMR and LC-MS analysis. Clorobiocin production was successfully restored in the cloN2 mutant by introducing a replicative plasmid containing the cloN2 sequence. These results prove an involvement of cloN2 in the formation of the ester bond between the pyrrole moiety and the deoxysugar in clorobiocin biosynthesis. Furthermore, they indicate that the C-methylation at position 5 of the pyrrole moiety occurs after the attachment of pyrrole-2-carboxylic acid unit to the deoxysugar moiety.

Agrifood by-products and microalgae represent a low-cost and valuable source of bioactive compounds with neuroprotective properties. However, the neuroprotective effectiveness of therapeutic molecules can be limited by their capacity to cross the blood–brain barrier (BBB) and reach the brain. In this research, various green extracts from Robinia pseudoacacia (ASFE), Cyphomandra betacea (T33), Coffea arabica (PPC1), Olea europaea L., (OL-SS), Citrus sinensis (PLE100) by-products and from the microalgae Dunaliella salina (DS) that have demonstrated in vitro neuroprotective potential were submitted to an in vitro BBB permeability and transport assay based on an immortalized human brain microvascular endothelial cells (HBMEC) model. Toxicity and BBB integrity tests were performed, and the transport of target bioactive molecules across the BBB were evaluated after 2 and 4 h of incubation using gas and liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (GC/LC-Q-TOF-MS). The HBMEC-BBB transport assay revealed a high permeability of representative neuroprotective compounds, such as mono- and sesquiterpenoids, phytosterols and some phenolic compounds. The obtained results from the proposed in vitro BBB cellular model provide further evidence of the neuroprotective potential of the target natural extracts, which represent a promising source of functional ingredients to be transferred into food supplements, food additives, or nutraceuticals with scientifically supported neuroprotective claims.

In the present study, the role of a novel protein involved in neurite development and endoplasmic reticulum (ER) stress, canopy homolog 2 (CNPY2), was investigated in mouse and human hepatocarcinogenesis. Firstly, a sensitive quantitative and qualitative detection of protein expression using QSTAR Elite LC-Ms/Ms was performed for the analysis of lysates of microdissected hepatocellular altered foci (AF), adenomas (HCAs), carcinomas (HCCs) and peri-tumoral livers from C57Bl/6J mice treated with diethylnitrosamine (DEN) and then maintained for 27 or 38 weeks on basal diet. Significant overexpression of 18.5 kDa CNPY2 processed form was demonstrated in AF, HCAs and HCCs, while low expression was observed in the livers of DEN-treated and control mice. Furthermore, CNPY2 elevation in AF and tumors was coordinated with accumulation of numerous cytoskeletal proteins, including cytokeratins 8 and 18, actin, non-muscle myosin and septin 9 and those involved in ER and mitochondrial stresses such as calreticulin, prohibitins 1 and 2 and YME1-like-1. Knockdown of CNPY2 in Huh7 and HepG2 human liver cancer cells resulted in significant suppression of cell survival and invasive potential, inhibition of cyclin D1, induction of p21Waf1/Cip1 and suppression of the apoptosis inhibitor Bcl2. In contrast, transfection of a mouse CNPY2 (mCNPY2-Ds-Red) vector plasmid in Huh7 and HepG2 cancer cells, with subsequent accumulation of CNPY2 in the ER, resulted in significant increase in cancer cells survival. Clinicopathological analysis in 90 HCV-positive HCC patients, revealed significant association of CNPY2 overexpression with poor overall (p = 0.041) survival. Furthermore, CNPY2 increase was associated with vessel invasion (p = 0.038), poor histological differentiation (p = 0.035) and advanced clinical stage (p = 0.016). In conclusion, CNPY2 is a promising molecular target elevated early in hepatocarcinogenesis and prognostic marker for human HCV-associated HCC. CNPY2 is involved in the processes of ER stress, cell cycle progression, proliferation, survival and invasion of liver tumor cells.

Abstract The zinc finger transcription factor GATA-1 is required for proliferative inhibition and terminal maturation of megakaryocytes, and is mutated in Down Syndrome Transient Myeloproliferative Disorder (TMD) and Acute Megakaryoblastic Leukemia (DS-AMKL). Yet the molecular mechanisms that regulate GATA-1 activity in megakaryopoiesis remain incompletely understood. Many transcription factors, in addition to binding DNA, make important protein-protein interactions that modulate their activity. In order to further understand GATA-1’s function, and possibly identify new factors involved in megakaryopoiesis, we purified GATA-1 containing multiprotein complexes from the murine L8057 megakaryocytic cell line. We generated stable L8057 cell lines expressing metabolically biotinylated and FLAG epitope tagged GATA-1, and then performed a tandem anti-FLAG immunoaffinity and streptavidin affinity purification. Using mass spectrometry (LC/MS/MS), we identified the known GATA-1 associated proteins Friend of GATA-1 (FOG-1), SCL, Ldb1, Runx-1/Cbf-β. SP1 and all components of the NuRD complex (which binds FOG-1) as co-purifying proteins. In addition, we reproducibly obtained several novel proteins. We previously reported the identification of the kruppel-type zinc finger transcription factor zfp148 (also called ZBP-89), and showed that it plays an essential role in megakaryopoiesis and definitive erythropoiesis. Here we report the identification of Kindlin 3 (also called URP2 for UNC-112 related protein 2), a member of a family of PH and FERM domain containing proteins that are thought to play a role in integrin-mediated processes. Expression of Kindlin 3 is restricted to hematopoietic cells, principally megakaryocytes and lymphocytes. It is first expressed at ~E9.5 during murine embryogenesis, and is abundant in fetal liver megakaryocytes by day E14.5. In order to begin to assess the role of Kindlin 3 in megakaryopoiesis in vivo, we performed morpholino-mediated knockdown of Kindlin 3 expression in CD41-GFP transgenic zebrafish embryos. In contrast to control embryos, embryos injected with Kindlin 3 specific morpholinos exhibited nearly complete loss of GFP+ thrombocytes (equivalent to mammalian megakaryocyte/platelets). Erythroid development (equivalent to mammalian primitive erythropoiesis at this stage of development) was not significantly affected, similar to embryos injected with zfp148-specific morpholinos. Given the role of integrin outside-to-inside signaling in megakaryopoiesis, we propose that Kindlin 3 may play a role linking extracellular signals to megakaryocyte maturation and growth control via GATA-1 transcription complexes. Further analysis in murine systems is underway to test this hypothesis.

Methyl cellulose and its derivatives are widely used in the food industry, cosmetics, and as construction materials. The properties of methyl celluloses (MC) strongly depend on their degrees and positions of substitution. In order to generate MCs with uncommon blocky substitution, we apply fully protected O-benzyl-O-methyl celluloses (BnMC). Such complex polysaccharide derivatives could not be deprotected completely and without shift of the composition by methods usually applied to mono- and oligosaccharides. Therefore, a facile debenzylation method was developed based on photo-initiated free-radical bromination in the presence of hydrobromic acid scavengers followed by alkaline treatment. The reaction proceeds under homogeneous conditions and without the aid of any catalyst. There is no need for expensive equipment, materials, anhydrous reagents, or running the reaction under anhydrous conditions. Reaction parameters were investigated and optimized for successful debenzylation of completely protected BnMC with degrees of methyl substitution (DSMe) around 1.9 (and DSBn around 1.1). Side-product-free and almost complete debenzylation was achieved when 1,2-epoxybutane (0.5 eq./eq. N-bromosuccinimide) and 2,6-di-tert-butylpyridine (0.5 eq./eq. N-bromosuccinimide) were used in the reaction. Furthermore, ATR-IR and 1H NMR spectroscopy confirmed the successful removal of benzyl ether groups. The method was developed to monitor the transglycosylation reaction of the BnMC with permethylated cellulose, for which the deprotection of many small samples in parallel is required. This comprises the determination of the methyl pattern in the glucosyl units by gas-liquid chromatography (GLC), as well as oligosaccharide analysis by liquid chromatography mass spectrometry (LC-MS) after perdeuteromethylation and partial hydrolysis to determine the methyl pattern in the chains. The unavoidable partial chain degradation during debenzylation does not interfere with this analytical application, but, most importantly, the DS and the methyl pattern were almost congruent for the debenzylated product and the original MC, indicating the full success of this approach The presented method provides an unprecedented opportunity for high throughput and parallel debenzylation of complicated glucans, such as BnMC (as a model compound), for analytical purposes. For comparison, debenzylation using Na/NH3 was applied to BnMC and resulted in a completely debenzylated product with a remarkably high recovery yield of 99 mol% and is, thus, the method of choice for synthetic applications, e.g., for the transglycosylation product prepared under the selected conditions in a preparative scale.

The phthalate and semi-volatile organic compounds (SVOCs) are modern chemical substances and extensively existing in the indoor environment. The European Commission stipulated the “European Unified Test Criteria”, since 2011, for the declared specifications of building products (CEN/TS 16516), based on the “lowest concentrations of interest (LCI)”, the index pollutants, test method, and emission standard of “phthalate” and “SVOC” were specified in detail. The purpose of this study is to use six common indoor floor construction products in Taiwan (regenerated pseudoplastic rubber flooring, healthy pseudoplastic imitation wood floor, regenerated pseudoplastic rubber flooring, PVC floor tile/floor, plastic click floor, composite floor covered with carpet) to detect the changes in the concentration of phthalate emitted to the air. The ISO 16000-25 Indoor air—Part 25: Determination of the emission of semi-volatile organic compounds by building products—micro-chamber method is used to build a DS-BMEMC (glass micro-chamber: volume 630 mL), the SVOC, including phthalate, is collected in two stages, in the stable conditions of temperature 25 °C, relative humidity 50% and air change rate 2 times/h, the Stage 1 emission detection experiment (24 h) is performed, and then the Stage 2 heating-up desorption emission detection experiment (40 min air sampling) is performed, the temperature rises to 200–220 °C, the phthalate and SVOC adsorbed on the glass micro-chamber is desorbed at a high temperature to catch the air substances, the air is caught by Tenax®—TA and Florisil® adsorption tube, and then the GC/MS and LC/MSMS analysis methods are used for qualitative and emission concentration analyses of SVOC of two-stage emission, respectively. The findings show that the floor construction materials emit nine phthalate SVOCs: DEHP, DINP, DNOP, DIDP, BBP, DBP, DIBP, DEP, and DMP, the two-stage emission concentrations are different, Stage 1 (normal temperature) emission concentration of six floor construction materials is 0.01–1.2% of Stage 2 (high temperature) emission concentration, meaning the phthalate SVOC of floor construction materials is unlikely to be volatilized or emitted at normal temperature. An interesting finding is that only S3 was detected DINP 72.6 (μg/m3) in stage 1. Others were detected DINP in stage 2. This might be because S3 has carpet on the surface. This implies that floor material with carpet may have an emission of DINP at normal temperature. The result of this study refers to the limited value evaluation of EU structural material standard emission TSVOC ≤ 0.1 ug/m3, the floor building material emissions are much higher than the evaluation criteria, increasing the health risk of users. The detection method and baseline can be used as the standard for controlling the emission of phthalate SVOC of Taiwan’s green building material labeling system in the future.

A higiene bucal, parte integrante dos cuidados corporais, é realizada com o auxílio de dispositivos, em especial, a escova dental. Com a evolução tecnológica, as escovas dentais passaram a ser fabricadas com diferentes materiais. Objetivou-se investigar as marcas e modelos de escovas dentárias disponíveis no mercado brasileiro; analisar a legislação vigente sobre a produção e verificar as informações fornecidas pelo fabricante ao consumidor final. Trata-se de um estudo transversal, descritivo, qualitativo, de análise documental. Foi realizado levantamento nas páginas eletrônicas da Agencia Nacional de Vigilância Sanitária e do Instituto Nacional de Metrologia, Qualidade e Tecnologia sobre a legislação vigente, que estabelece as características exigidas para produção e comercialização de escovas dentárias. Foram pesquisadas marcas e modelos disponíveis no mercado brasileiro, nas páginas eletrônicas das empresas, fabricantes ou importadoras e em pontos de vendas para o consumidor final para verificar as informações disponíveis nas embalagens. A Resolução N° 54/17 da Diretoria Colegiada da ANVISA, estabelece algumas características físicas, tais como: largura máxima da cabeça e comprimento mínimo da escova dentária. Foram incluídos nesta pesquisa 20 marcas comerciais, as quais distribuem 108 modelos no mercado brasileiro. Apenas 2 modelos (1,85%) apresentaram todas as informações exigidas pela resolução da ANVISA, sendo a “supervisão do adulto” e “orientação do dentista” os itens menos contemplados. Não apresentaram indicação para uso adulto ou infantil 44,4% do total. Conclui-se, que existem muitas marcas e modelos no mercado brasileiro, porém faltam informações importantes para o profissional realizar a indicação apropriada e o paciente, a aquisição consciente. 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Background: Although sleep has been identified as an important modifiable risk factor for sports injury, the effect of decreased sleep on sports injuries in adolescents is poorly studied. Purpose: To systematically review published literature to examine if a lack of sleep is associated with sports injuries in adolescents and to delineate the effects of chronic versus acute lack of sleep. Methods: PubMed and EMBASE databases were systematically searched for studies reporting statistics regarding the relationship between sleep and sports injury in adolescents aged <19 years published between 1/1/1997 and 12/21/2017. From included studies, the following information was extracted: bibliographic and demographic information, reported outcomes related to injury and sleep, and definitions of injury and decreased sleep. Additionally, a NOS (Newcastle-Ottawa Scale) assessment and an evaluation of the OCEM (Oxford Center for Evidence-Based Medicine) level of evidence for each study was conducted to assess each study’s individual risk of bias, and the risk of bias across all studies. Results: Of 907 identified articles, 7 met inclusion criteria. Five studies reported that adolescents who chronically slept poorly were at a significantly increased likelihood of experiencing a sports or musculoskeletal injury. Two studies reported on acute sleep behaviors. One reported a significant positive correlation between acutely poor sleep and injury, while the other study reported no significant correlation. In our random effects model, adolescents who chronically slept poorly were more likely to be injured than those who slept well (OR 1.58, 95% CI 1.05 to 2.37, p = 0.03). OCEM criteria assessment showed that all but one study (a case-series) were of 2b level of evidence—which is the highest level of evidence possible for studies which were not randomized control trials or systematic reviews. NOS assessment was conducted for all six cohort studies to investigate each study’s individual risk of bias. Five out of six of these studies received between 4 to 6 stars, categorizing them as having a moderate risk of bias. One study received 7 stars, categorizing it as having a low risk of bias. NOS assessment revealed that the most consistent source of bias was in ascertainment of exposure: all studies relied on self-reported data regarding sleep hours rather than a medical or lab record of sleep hours. Conclusions: Chronic lack of sleep in adolescents is associated with greater risk of sports and musculoskeletal injuries. Current evidence cannot yet definitively determine the effect of acute lack of sleep on injury rates. 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The pandemic of COVID-19 has afflicted every individual and has initiated a cascade of directly or indirectly involved events in precipitating mental health issues. The human species is a wanderer and hunter-gatherer by nature, and physical social distancing and nationwide lockdown have confined an individual to physical isolation. The present review article was conceived to address psychosocial and other issues and their aetiology related to the current pandemic of COVID-19. The elderly age group has most suffered the wrath of SARS-CoV-2, and social isolation as a preventive measure may further induce mental health issues. Animal model studies have demonstrated an inappropriate interacting endogenous neurotransmitter milieu of dopamine, serotonin, glutamate, and opioids, induced by social isolation that could probably lead to observable phenomena of deviant psychosocial behavior. Conflicting and manipulated information related to COVID-19 on social media has also been recognized as a global threat. Psychological stress during the current pandemic in frontline health care workers, migrant workers, children, and adolescents is also a serious concern. Mental health issues in the current situation could also be induced by being quarantined, uncertainty in business, jobs, economy, hampered academic activities, increased screen time on social media, and domestic violence incidences. The gravity of mental health issues associated with the pandemic of COVID-19 should be identified at the earliest. Mental health organization dedicated to current and future pandemics should be established along with Government policies addressing psychological issues to prevent and treat mental health issues need to be developed. References World Health Organization (WHO) Coronavirus Disease (COVID-19) Dashboard. 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Objective: The technology, network pharmacology and molecular docking technology of the ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) were used to explore the potential molecular mechanism of Platycodon grandiflorum (PG) in the treatment of lung cancer (LC).Methods: UPLC-Q-TOF-MS/MS technology was used to analyze the ingredients of PG and the potential LC targets were obtained from the Traditional Chinese Medicine Systems Pharmacology database, and the Analysis Platform (TCMSP), GeneCards and other databases. The interaction network of the drug-disease targets was constructed with the additional use of STRING 11.0. The pathway enrichment analysis was carried out using Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) in Metascape, and then the “Drug-Ingredients-Targets-Pathways-Disease” (D-I-T-P-D) network was constructed using Cytoscape v3.7.1. Finally, the Discovery Studio 2016 (DS) software was used to evaluate the molecular docking.Results: Forty-seven compounds in PG, including triterpenoid saponins, steroidal saponins and flavonoids, were identified and nine main bioactive components including platycodin D were screened. According to the method of data mining, 545 potential drug targets and 2,664 disease-related targets were collected. The results of topological analysis revealed 20 core targets including caspase 3 (CASP3) and prostaglandin-endoperoxide synthase 2 (PTGS2) suggesting that the potential signaling pathway potentially involved in the treatment of LC included MAPK signaling pathway and P13K-AKT signaling pathway. The results of molecular docking proved that the bound of the ingredients with potential key targets was excellent.Conclusion: The results in this study provided a novel insight in the exploration of the mechanism of action of PG against LC.

AbstractBackground:The systematic evaluation of the clinical concordance of various 25-hydroxyvitamin D (25OHD) testing methods is presented. The need for this approach is raised by the discrepancies in the analytical performance of the available assays.Methods:The analytical and clinical performance of six automated 25OHD assays and an in-house liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was investigated. Leftover serum samples (n=162, SA: n=114) were analyzed and all 21 assay combinations were evaluated. The utility of Cohen’s κ values was assessed by transforming them into minimum percentage agreement (MPA). McNemar’s hypothesis test was employed for testing the symmetry of the disagreeing classification outcomes within each method pair.Results:Depending on the assay method, the ratio of results classified as positive (<20 ng/mL) was 13.5%–40.0%. The percentage agreement (PA) was 74.1%–92.6%. Compared to other methods, significantly more hypovitaminosis cases were delivered by DiaSorin Liaison® 25 OH vitamin D Total (DL) and significantly fewer by IDS-iSYS 25-Hydroxy Vitamin DS (II). The strongest clinical concordance was exerted by II vs. LC-MS/MS. The κ-derived MPA showed close similarity to the PA scores. McNemar’s tests confirmed the asymmetry of the disagreement in the classification in 14 method combinations.Conclusions:The presented approach allows the prediction of the clinical consequences of a 25OHD method transfer. Differences in the clinical classification of assay results are likely encountered when transferring to a new method, even between assays standardized according to the Vitamin D Standardization Program (VDSP) Reference Method Procedure (RMP).

Perineuronal nets (PNNs) are extracellular matrix (ECM) structures that enmesh and regulate neurocircuits involved in motor and sensory function. Maladaptive changes to the composition and/or abundance of PNNs have been implicated in preclinical models of neuroinflammation and neurocircuit destabilization. The central nervous system (CNS) is limited in its capacity to repair and reorganize neural networks following traumatic brain injury (TBI) and little is known about mechanisms of ECM repair in the adult brain after TBI. In this study, adult male C57BL/6 mice were subjected to a TBI via a controlled cortical impact (CCI) to the right motor and somatosensory cortices. At 7 days following CCI, histological analysis revealed a loss of Wisteria floribunda agglutinin (WFA) positive PNN matrices in the ipsilateral cortex. PNNs are comprised of chondroitin sulfate (CS) and dermatan sulfate (DS)-glycosaminoglycans (GAGs), the composition of which are known to influence neuronal integrity and repair. Using an innovative liquid chromatography tandem mass spectrometry (LC-MS/MS) method, we analyzed the relative abundance of six specific CS/DS-GAG isomers (Δ4S-, Δ6S-, Δ4S6S-, Δ2S6S-, Δ0S-CS, and Δ2S4S-DS) from fixed-brain sections after CCI injury. We report a significant shift in CS/DS-GAG sulfation patterns within the rostro-caudal extent of the injury site from mice exposed to CCI at 7 days, but not at 1 day, post-CCI. In the ipsilateral thalamus, the appearance of WFA+ puncta occurred in tandem with gliosis at 7 days post-CCI, but weakly colocalized with markers of gliosis. Thalamic WFA+ puncta showed moderate colocalization with neuronal ubiquitin C-terminal hydrolase L1 (UCHL1), a clinical biomarker for TBI injury. A shift in CS/DS-GAG sulfation was also present in the thalamus including an increase of 6S-CS, which is a specific isomer that associates with the presence of glial scarring. Upregulation of the 6S-CS-specific sulfotransferase (CHST3) gene expression was accompanied by reactive gliosis in both the ipsilateral cortex and thalamus. Moreover, changes in 6S-CS extracted from the thalamus positively correlated with deficits in motor coordination after CCI. Collectively, these data argue that CCI alters CS/DS-GAG sulfation in association with the spatiotemporal progression of neurorepair. Therapeutic interventions targeting restoration of CS/DS-GAG sulfation patterns may improve outcomes from TBI.

Down syndrome (DS) is mainly caused by an extra copy of chromosome 21 (trisomy 21), and patients display a variety of developmental symptoms, including characteristic facial features, physical growth delay, intellectual disability, and neurodegeneration (i.e., Alzheimer’s disease; AD). One of the pathological hallmarks of AD is insoluble deposits of neurofibrillary tangles (NFTs) that consist of hyperphosphorylated tau. The human DYRK1A gene is mapped to chromosome 21, and the protein is associated with the formation of inclusion bodies in AD. For example, DYRK1A directly phosphorylates multiple serine and threonine residues of tau, including Thr212. However, the mechanism underpinning DYRK1A involvement in Trisomy 21-related pathological tau aggregation remains unknown. Here, we explored a novel regulatory mechanism of DYRK1A and subsequent tau pathology through a phosphatase. Using LC-MS/MS technology we analyzed multiple DYRK1A-binding proteins, including PPM1B, a member of the PP2C family of Ser/Thr protein phosphatases, in HEK293 cells. We found that PPM1B dephosphorylates DYRK1A at Ser258, contributing to the inhibition of DYRK1A activity. Moreover, PPM1B-mediated dephosphorylation of DYRK1A reduced tau phosphorylation at Thr212, leading to inhibition of toxic tau oligomerization and aggregation. In conclusion, our study demonstrates that DYRK1A autophosphorylates Ser258, the dephosphorylation target of PPM1B, and PPM1B negatively regulates DYRK1A activity. This finding also suggests that PPM1B reduces the toxic formation of phospho-tau protein via DYRK1A modulation, possibly providing a novel cellular protective mechanism to regulate toxic tau-mediated neuropathology in AD of DS.

AbstractAmyloid plaques contain many proteins in addition to beta amyloid (Aβ). Previous studies examining plaque-associated proteins have shown these additional proteins are important; they provide insight into the factors that drive amyloid plaque development and are potential biomarkers or therapeutic targets for Alzheimer’s disease (AD). The aim of this study was to comprehensively identify proteins that are enriched in amyloid plaques using unbiased proteomics in two subtypes of early onset AD: sporadic early onset AD (EOAD) and Down Syndrome (DS) with AD. We focused our study on early onset AD as the drivers of the more aggressive pathology development in these cases is unknown and it is unclear whether amyloid-plaque enriched proteins differ between subtypes of early onset AD. Amyloid plaques and neighbouring non-plaque tissue were microdissected from human brain sections using laser capture microdissection and label-free LC–MS was used to quantify the proteins present. 48 proteins were consistently enriched in amyloid plaques in EOAD and DS. Many of these proteins were more significantly enriched in amyloid plaques than Aβ. The most enriched proteins in amyloid plaques in both EOAD and DS were: COL25A1, SMOC1, MDK, NTN1, OLFML3 and HTRA1. Endosomal/lysosomal proteins were particularly highly enriched in amyloid plaques. Fluorescent immunohistochemistry was used to validate the enrichment of four proteins in amyloid plaques (moesin, ezrin, ARL8B and SMOC1) and to compare the amount of total Aβ, Aβ40, Aβ42, phosphorylated Aβ, pyroglutamate Aβ species and oligomeric species in EOAD and DS. These studies showed that phosphorylated Aβ, pyroglutamate Aβ species and SMOC1 were significantly higher in DS plaques, while oligomers were significantly higher in EOAD. Overall, we observed that amyloid plaques in EOAD and DS largely contained the same proteins, however the amount of enrichment of some proteins was different in EOAD and DS. Our study highlights the significant enrichment of many proteins in amyloid plaques, many of which may be potential therapeutic targets and/or biomarkers for AD.

Introduction: Puerto Rican adults living on the US mainland tend to have poor quality diets and adverse cardiometabolic risk. Plasma metabolomic signatures reflect dietary intakes and variability in metabolic response to diet. Hypothesis: A plasma metabolomic signature reflecting adherence to the American Heart Association (AHA) dietary guidelines will be associated with cardiometabolic risk. Methods: We used LC/MS to measure plasma metabolites (>700) among Boston Puerto Rican Health Study participants, aged 45-75 years, without (n=252) and with (n=254) type 2 diabetes (T2D). We calculated a modified version of a previously validated AHA diet score (AHA-DS), which included variety and amounts of fruits/vegetables, whole grains, fish, saturated fat, trans fat, sodium, and added sugars. We used elastic net regression to identify a metabolomic signature that associated with higher adherence to the AHA-DS among those without T2D (training set) and replicated the associations among those with T2D (testing set). A metabolomic score was calculated as the weighted sum of the diet associated metabolites. We used general linear models to determine the cross-sectional associations between the AHA-DS, metabolomic score, and cardiometabolic risk factors. Results: A diet-associated metabolomic signature with 58 metabolites, primarily lipids and amino acids, was identified. This metabolomic score correlated moderately with the AHA-DS among those with and without T2D (r=0.42-0.46, P <5.7x10 -12 ). In all participants (n=506), the metabolomic score, but not the AHA-DS, was significantly associated with higher HDL-C and LDL-C concentrations, and lower waist circumference ( P <0.004; Table 1). No associations were observed for triglyceride concentrations, glycemia measures, or blood pressure. Conclusions: In individuals of Puerto Rican descent, we identified a metabolomic signature that reflected adherence and metabolic response to the AHA dietary guidelines and that associated with cardiometabolic risk factors.

Abstract Background Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor drug for treating premature ejaculation. This study was designed to develop and validate a sensitive and selective LC–MS/MS method for trace analysis of genotoxic impurity ethyl methanesulfonate in Dapoxetine hydrochloride. Results Chromatographic separation was achieved on the Shodex RSpak DS-413 column, 150 × 4.6 mm, 3.0 µm using eluent containing a equal volumes of acetonitrile and 0.1% v/v formic acid in water was used in the isocratic elution mode at a pump flow of 1.0 mL/min. No interference was observed at the retention time of ethyl methanesulfonate, indicating that the developed method is specific and selective for trace level quantification.The developed method was found to be linear in the concentration range of 1–50 ppm with coefficient of regression of 0.9997. Detection limit and quantification limit were determined to be 0.6 ppm and 1.0 ppm respectively. Acceptable RSD values (< 10.0%) and recovery results (> 90%) obtained from the accuracy and precison experiments indicate that the developed method is precise and accurate in the concentration range of 1–50 ppm. Ethyl methanesulfonate solutions were stable for two days when stored at room and refrigerated temperatures. Conclusion The developed method has the ability to quantify ethyl methanesulfonate in dapoxetine hydrochloride. Thus, the anticipated method has high probability to adopt in the quality testing laboratories of pharmaceutical industry.

Introduction: Puerto Rican (PR) adults living on the US mainland are at high risk for developing type 2 diabetes (T2D), and dietary factors may contribute to this increased risk. Network analysis is a data-reduction tool that can identify correlated clusters of co-regulated metabolites that reflect mechanisms underlying diet-T2D associations. Hypothesis: Diet quality will associate with T2D-associated metabolite clusters among PR adults. Methods: We used LC/MS to measure fasting plasma metabolites (>700) among Boston PR Health Study participants, aged 45-75 years, with (n=258) and without (n=421) T2D. We applied an unsupervised correlation network-based method to identify metabolite clusters within a global metabolite network and calculated a score for each cluster using a weighted sum of metabolite concentrations. To estimate diet quality, we calculated a modified version of a previously validated American Heart Association diet score (AHA-DS). Logistic regression was used to assess cross-sectional associations between metabolite clusters and prevalent T2D, and linear regression was used to assess associations between the continuous AHA-DS and T2D-associated metabolite clusters among controls, adjusting for potential confounders and correcting for multiple testing. Results: We identified 7 metabolite clusters that were associated with prevalent T2D ( p <0.05). For every 1-standard deviation (SD) increase in cluster score, the odds ratios for prevalent T2D and 95% confidence intervals were as the follows: acylcholines [0.40 (0.31, 0.50)], aromatic hydrocarbon derivatives [0.33 (0.22, 0.47)], sphingolipids [0.46 (0.33, 0.64)], tricarboxylic acid (TCA) cycle amino acids/peptides [0.39 (0.25, 0.62)], branched-chain amino acid metabolites [4.1 (2.9, 6.0)], acylcarnitines [1.8 (1.3, 2.5)], and TCA cycle/energy metabolites [2.0 (1.4, 3.0)]. The AHA-DS was only significantly associated with the acylcholine metabolites cluster [β (standard error) = 0.01 (0.004) SD increase in cluster score, p=0.02]. Conclusions: In individuals of PR descent, we identified a cluster of acylcholine metabolites where concentrations are higher among those with better diet quality and lower among those with prevalent T2D.

Os casos de neuralgia do trigêmeo no âmbito da Odontologia merecem, ainda, maior atenção devido ao difícil e criterioso diagnóstico desta condição que, muitas vezes, acaba confundida com outras patologias associadas às dores orofaciais. Este trabalho visa relatar o caso de uma paciente idosa edêntula com quadros de dor em topografia de nervo mentual direito, com sensibilização em mucosa gengival e lábio inferior à direita, compatível com neuralgia trigeminal, a qual foi tratada com indução à neurólise do nervo mentual direito por necrose asséptica estimulada por solução alcoólica. A paciente encontra-se com dois anos de acompanhamento e sem os episódios de dor. Mesmo o processo de diagnóstico sendo extenso e exigindo muito critério, foi possível diagnosticar a nevralgia da paciente e empregar o passo-a-passo do tratamento, chegando a melhor opção para este caso, que foi a alcoolização do nervo mentual.Descritores: Neuralgia Facial; Neuralgia; Neuralgia do Trigêmeo; Bloqueio Nervoso.ReferênciasSiqueira SRDT, Siqueira JTT. Neuralgia do trigêmeo: diagnóstico diferencial com odontalgias. APCD. 2003.Leocádio JCM, Santos LC, Sousa MCA, Gonçalves NJC, Campos IC. Neuralgia do trigêmeo: uma revisão de literatura. Braz J Surg Clin Res. 2014;7(2):33-7.Headache Classification Subcommitte of the International Headache Society. The International Classification of Headache Disorders. 2nd ed. Cephalalgia. 2004;24(Suppl):9-160.Quesada GAT, Baptista CE, Pedroso DS, Flores DL. Neuralgia trigeminal: do diagnóstico ao tratamento. Rev Dentíst Online. 2005;5(11):46-54.Bertoli FMP, Koczicki VC, Meneses MS. A neuralgia do trigêmeo: um enfoque odontológico. JBA. 2003;3(10):125-29.Classificação Internacional de Cefaleias. 3. ed. 2014. Disponível em: https://www.ichd-3.org/wp-content/uploads/2016/08/2087_ichd-3-beta-versao-pt-portuguese.pdf. Acesso em 04 out 2018.Domingues RB, Kuster GW, Aquino CCH. Treatment of trigeminal neuralgia with low doses of topiramate. Arq Neuropsiquiatr. 2007;65(3B):792-94.Borbolato RM, Ambiel CR. Neuralgia do trigêmeo: aspectos importantes na clínica odontológica. Saúde e Pesquisa. 2009;2(2):201-8.Mattos JMB, Bueno FV, Mattos LR. Neuralgia do trigêmeo: um novo protocolo de tratamento clínico. Rev Dor. 2005;6(4):652-56.Kitt CA, Gruber K, Davis M, Woolf CJ, Levine JD. Trigeminal neuralgia: opportunities for research and treatment. Pain. 2000;85(1-2):3-7.Frizzo HM, Hasse PN, Veronese RM. Neuralgia do trigêmeo: revisão bibliográfica analítica. Rev Cir Traumatol Buco-Maxilo-Facial. 2004;4(4):212-17.Alves TCA, Azevedo GS, Carvalho ES. Tratamento farmacológico da neuralgia do trigêmeo: revisão sistemática e metanálise. Rev Bras Anestesiol. 2004;54(6):836-49.Felix F, Olivaes MCD, Gismondi RAOC, Belmont H, Felix JAP. Tratamento conservador da síndrome de Gradenigo. Rev Bras Otorrinol. 2003;69(2):256-59.Okeson JP. Dores bucofaciais de Bell: tratamento clínico da dor bucofacial. 6. ed. São Paulo: Quintessence, 2006.Poluha RL, Silva RS. Neuralgia do trigêmeo – V3: relato de caso. Rev Uningá. 2015;45(1):40-2.

Abstract Consumption of foods and dietary supplements (DS) adulterated with unprescribed or non-permitted phosphodiesterase-5 inhibitors (PDE-5i) and their analogs can cause serious risk to human health. This study aims to analyze 93 PDE-5i and their analogs present in adulterated foods and DS using an established and validated method involving high-performance liquid chromatography (HPLC). The method was validated in solid and liquid samples, resulting in a limit of detection and quantitation of 0.03–0.5 and 0.08–1.6 μg/mL, respectively. Using the validated method, a total of 404 samples were screened. It was found that 32% of 404 samples were illegally adulterated with PDE-5i and their analogs; moreover, 16.9% of the adulterated samples were found to contain more than three compounds. HPLC-quadrupole-time-of-flight (TOF)/mass spectrometry (MS) analysis was conducted on all the samples to confirm the detected compounds accurately based on fragmentation ion patterns. In addition, sildenafil and tadalafil were detected from the capsule shells of DS unusually. Subsequently, the detected compounds were identified and quantified using HPLC at concentrations ranging from 0.007 to 370.0 mg/g. NMR analysis was carried out to confirm the accurate chemical structure of a compound found during the TOF/MS analysis, which did not match with the 93 reference standards.; it was identified to be N-desmethylthiosildenafil. In this study, various PDE-5i compounds and their analogs were detected from low to high concentrations in a sample. Therefore, the study sheds light on the misuse of PDE-5i and their analogs in consumable products, which pose a severe threat to public health.

O parto pré-termo, é aquele que ocorre antes da 37ª semana de gestação, e é o problema perinatal atual mais importante, pois está associado à morbidade e mortalidade significativas no início da vida. O objetivo do estudo foi caracterizar o nascimento de pré-termos entre mulheres residentes no Estado do Piauí, no período entre 2011 a 2015. Trata-se de estudo descritivo utilizando os dados do Sistema de Informações sobre Nascidos Vivos (SINASC) coletados do banco de dados do Departamento de Informática do Sistema Único de Saúde (DATASUS). A população foi constituída por 23.754 nascidos vivos, sendo 26.182 pré-termos. Houve aumento percentual do número de recém-nascidos pré-termos entre os anos estudados. Observou-se que idade materna variou entre 20 e 34 anos, a maioria das mães eram casadas, com escolaridade de 8 a 11 anos, de gravidez única, com 7 consultas pré-natal ou mais, recém-nascido de raça/cor parda relacionaram-se com o nascimento pré-termo. Partos vaginais, recém-nascidos do sexo masculino, também se relacionaram à prematuridade, assim como, a influência da situação socioeconômica. Os recém-nascidos pré-termos caracterizaram-se principalmente por serem de 32 a 36 semanas, sexo masculino, pardos e peso normal ao nascer. Assim, os dados obtidos permitem concluir que o conhecimento e a avaliação do perfil das mães e o número e a situação do nascimento dessas crianças é importante no planejamento de estratégias de saúde eficazes na atenção materno-infantil, objetivando aprimorar políticas públicas para a sobrevivência do recém-nascido e a consequente redução da ocorrência da prematuridade.Descritores: Recém-Nascido Prematuro; Declaração de Nascimento; Sistemas de Saúde.ReferênciasMontenegro RF. Obstetrícia fundamental. Rio de Janeiro: Guanabara Koogan; 2008.Saigal S, Doyle LW. An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet. 2008;371(9608):261-69.Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008;371(9606):75-84.Bettiol H, Rona RJ, Chinn S, Goldani M, Barbieri MA. Factors associated with preterm births in southeast Brazil: a comparison of two birth cohorts born 15 years apart. Paediatr Perinat Epidemiol. 2000;14(1):30-8.Barros FC, Victora CG, Barros AJ, Santos IS, Albernaz E, Matijasevich A, et al. The challenge of reducing neonatal mortality in middle-income countries: findings from three Brazilian birth cohorts in 1982, 1993, and 2004. Lancet. 2005;365(9462):847-54.De Farias Aragão VM, Barbieri MA, Moura Da Silva AA, Bettiol H, Ribeiro VS. Risk factors for intrauterine growth restriction: a comparison between two Brazilian cities. Pediatr Res. 2005;57(5 Pt 1):674-79.Blencowe H, Cousens S, Chou D, Oestergaard M, Say L, Moller AB et al. Born Too Soon: The global epidemiology of 15 million preterm births. Reprod Health. 2013;10(Suppl 1):S2. Martins MG, Santos GHN, Sousa MS, Costa JEFB, Simões VMF. Associação da gravidez na adolescência e prematuridade. Rev Bras Ginecol Obstet. 2011;33(11):354-60.Almeida MVL. Prematuridade. In: Chaves Netto H, Moreira de Sá RA. Obstetrícia básica. São Paulo: Atheneu; 2007.Kilsztajn S, Rossbach A, Carmo MSN, Sugahara GTL. Assistência pré-natal, baixo peso e prematuridade no Estado de São Paulo. Rev Saúde Pública. 2003;37(3):303-10.Cascaes AM, Gauche H, Baramarchi FM, Borges CM, Peres KG. Prematuridade e fatores associados no Estado de Santa Catarina, Brasil, no ano de 2005: análise dos dados do Sistema de Informações Sobre Nascidos Vivos. Cad Saúde Pública. 2008;24(5):1024-32.Silva LA, Silva RGA, Rojas PFB, Laus FF, Sakae TM. Fatores de risco associados ao parto pré-termo em hospital de referência de Santa Catarina. Rev AMRIGS. 2009;53(4):354-60.Costa CE, Gotlieb SLD. Estudo epidemiológico do peso ao nascer a partir da Declaração de Nascido Vivo. Rev Saude Publica. 1998; 32(4):328-34.Uchimura TT, Pelissari DM, Soares DFPP, Uchimura NS, Santana RG, Moraes CMS. Fatores de risco para o baixo peso ao nascer segundo as variáveis da mãe e do recém-nascido, em Maringá-PR, no período de 1996 a 2002. Cienc Cuid Saude. 2007;6(1):51-8.Brasil. Fundação Nacional de Saúde. Manual de instruções para o preenchimento da declaração de nascidos vivos. Brasília-DF; 2001.Silveira MF, Santos IS, Barros AJD, Matijasevich A, Barros FC, Victora CG. Aumento da prematuridade no Brasil: revisão de estudos de base populacional. Rev Saúde Pública. 2008;42(5):957-64.Silveira MF, Santos IS, Matijasevich A, Malta DC, Duarte EC. Nascimentos pré-termo no Brasil entre 1994 e 2005 conforme o Sistema de Informações Sobre Nascidos Vivos (SINASC). Cad Saúde Pública 2009;25(6):1267-75.Wen SW, Smith G, Yang Q, Walker M. Epidemiology of preterm birth and neonatal outcome. Semin Fetal Neonatal Med. 2004;9(6):429-35.Rodrigues LS, Batista RFL, Sousa ACV, Cantanhede JV, Costa LC. Caracterização dos recém-nascidos pré-termos nascidos em São Luís – MA no período de 2006 a 2010: análise do SINASC. Cad Pesq. 2012; 19(3):95-104.Giglio MRP, Lamounier JA, Morais Neto OL. Via de parto e mortalidade neonatal em Goiânia em 2000. Rev Saúde Pública. 2005; 39(3):350-57.Barros AJD, Santos IS, Victora CG, Albernaz EP, Domingues MR, Timm IK et al. Coorte de nascimentos de Pelotas, 2004: metodologia e descrição. Rev Saúde Pública. 2006;40(3):402-13.Silva RP, Caires BR, Nogueira DA, Moreira DS, Gradim CVC, Leite EPRC. Prematuridade: características maternas e neonatais segundo dados do sistema de informações sobre nascidos vivos. Rev enferm UFPE online. 2013;7(5):1349-55.Almeida MF, Guinsburg R, Martinez FE, Procianoy RS, Leone CR, Marba ST et al. Perinatal factors associated with early deaths of preterm infants born in Brazilian Networkon Neonatal Research centers. J Pediatr. 2008;84(4):300-7.Ramos HAC, Cuman RKN. Prematuridade e fatores de risco: pesquisa documental. Anna Nery. 2009;13(2):297-304.Aragão VMF, Silva AAM, Aragão LF, Barbieri MA, Bettiol H, Coimbra LC et al. Fatores de risco para prematuridade em São Luís, Maranhão, Brasil. Cad Saúde Pública 2004;20(1):57-63.Sampaio RMM, Pinto FJM, Sampaio JC. Fatores de risco associados à prematuridade em nascidos vivos no estado do Ceará. Rev baiana saúde pública. 2012;36(4):969-78.Dadorian D. Gravidez na adolescência: um novo olhar. Psicol cienc prof. 2003;23(1):84-91.Ferraz RT, Neves ET. Fatores de risco para baixo peso ao nascer em maternidades públicas. Rev Gaúcha Enferm. 2011;32(1):86-92.Almeida AC, Jesus ACP, Lima PFT, Araújo MFM, Araújo TM. Fatores de risco maternos para prematuridade em uma maternidade pública de Imperatriz- MA. Rev Gaúcha Enferm. 2012;33(2):86-94.Silva AAM, Ribeiro VS, Borba Júnior AF, Coimbra LC, Silva RA. Avaliação da qualidade dos dados do Sistema de Informações sobre Nascidos Vivos em 1997-1998. Rev Saúde Pública. 2001; 35(6):508-14.Salge AKM, Vieira AVC, Aguiar AKA, Lobo SF, Xavier RM et al. Fatores maternos e neonatais associados à prematuridade. Rev Eletr Enf. 2009;11(3):642-46.Caixeta FF, Corrêa MSNP. Os defeitos do esmalte e a erupção dentária em crianças prematuras. Rev Assoc Med Bras. 2005;51(4):195-99.

A Universidade responde pela formação de cidadãos com pensamento crítico, fundamentado em conceitos atualizados, capazes de favorecer uma postura dinâmica e participativa deste profissional na comunidade na qual estará inserido. A educação para o desenvolvimento sustentável, permeada pela articulação entre o conhecimento e os fenômenos sociais e culturais, traz consigo o desafio de incorporar habilidades, conferindo valores indispensáveis não só para o entendimento das relações históricas entre o ser humano e o ambiente, como também para a melhoria da qualidade de vida. A “Declaração Mundial sobre a Educação Superior para o Século XXI - Visão e Ação” pauta o processo educativo por sua missão em formar profissionais cidadãos, altamente esclarecidos, motivados, integrados e aptos a criarem uma sociedade fundamentada no amor à humanidade e na sabedoria. O equilíbrio entre as funções básicas de ensino, pesquisa e extensão dentro da Universidade concorre para que o educando se aproprie da construção de seu próprio conhecimento em uma perspectiva de formação integral do ser humano, ciente de sua responsabilidade social e política em prol de uma sociedade ambientalmente saudável. O presente trabalho tem o objetivo de, orientado pela revisão de literatura, construir algumas considerações sobre o papel da Universidade na educação para a sustentabilidade.Descritores: Universidades; Educação Superior; Educação Ambiental.ReferênciasBrasil. Identidades da Educação ambiental Brasileira. Brasília: DEA/MMA, 2004.Sato M. Educação Ambiental. São Carlos: Rima, 2002.Sorrentino M, Trajber R, Mendonça P, ferraro Jr. LA. Educação ambiental como política pública. Educ Pesq. 2005;31(2):285-99.Morales AGM. A formação do profissional educador ambiental [tese]. Curitiba: Programa em Meio Ambiente e Desenvolvimento, Universidade Federal do Paraná; 2007.Carvalho ICM. Educação ambiental: a formação do sujeito ecológico. São Paulo: Cortez; 2004.Gomes MAC. Educação para o Desenvolvimento Sustentável no contexto da década: discursos e práticas no ensino básico.[tese]. Lisboa: Instituto de Geografia e Ordenamento do Território, Universidade de Lisboa; 2012.Jacobi P. Educação ambiental: cidadania e sustentabilidade. Cad Pesqui. 2003;118(3):189-205.Guimaraes SSM, Tomazello MGC. A formação universitária para o ambiente: educação para a sustentabilidade. Ambiente e Educação. 2003, 55-71, 2003Sato M, Santos JE. A contribuição da educação ambiental à esperança de Pandora. São Carlos: Rima Editora, 2001. Piato RS, Capalbo LC, Alves Rezende MIR, Lehfeld LS, Alves Rezende MCR. O papel da Universidade Aberta à Terceira Idade na educação ambiental. Arch Health Invest. 2014;3(5):66-71.Menezes Neto PE. Universidade: ação e reflexão. 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La internacionalización de la educación superior: paradigma para la ciudadanía global. Guadalajara: Universidad de Guadalajara, 2003.Bernheim CT, Chaui MS. Challenges of the university in the knowledge society, five years after the World. Conference on Higher Education. Paris: UNESCO, 2003. Série Documentos Ocasionais de Fórum da UNESCO.Amin S. Capitalism in the age of globalization: the management of contemporary society. London: Zed Books, 1997.World Conference on Higher Education in the Twenty-first Century: Vision and Action; Paris; 1998. Paris: UNESCO, 1998.Brasil. Ministério da Educação. Secretaria de Educação Fundamental. Parâmetros curriculares nacionais: Vol. 1 – Introdução aos Parâmetros Curriculares Nacionais. Brasília: MEC/SEF, 1997.Brasil. Ministério da Educação. Secretaria de Educação Fundamental. Parâmetros curriculares nacionais: Vol. 8 – Apresentação dos Temas Transversais e Ética. Brasília: MEC/SEF, 1997.Marcomin FE, Silva ADV. 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Introdução: O termo ageismo é definido como uma forma de intolerância relacionada com a idade por meio de estereótipos, ou seja, qualquer pessoa poderia ser alvo de discriminação pela idade que tem, sendo os idosos um dos grupos mais vulneráveis. Teoricamente qualquer pessoa pode ser atingida pelo ageísmo ao longo de sua vida, desde que viva o suficiente para envelhecer. Objetivos: O propósito desse trabalho foi apresentar o papel das Universidades no combate ao ageísmo. Métodos: Para a elaboração do presente trabalho as seguintes etapas foram percorridas: estabelecimento da hipótese e objetivos do estudo; estabelecimento de critérios de inclusão e exclusão de artigos (seleção da amostra). Formulou-se a seguinte questão: as Universidades contribuem para a redução do ageísmo? Os artigos foram selecionados utilizando a base de dados The National Library of Medicine, Washington DC (MEDLINE – PubMed) e Google Scholar. As estratégias utilizadas para localizar os artigos tiveram como eixo norteador a pergunta e os critérios de inclusão da revisão, previamente estabelecidos para manter a coerência na busca dos artigos e evitar possíveis vieses. Como descritores foram utilizados os termos “Ageísmo”, “Universidades”; Expectativa de Vida” e “Relação entre Gerações”, acordando com o Decs. Os critérios de inclusão foram artigos publicados em inglês, espanhol e português com os resumos disponíveis, no período compreendido entre 1990-2020. A partir da pesquisa preliminar nas bases de dados, leitura do título e resumo, 20 artigos foram selecionados para leitura na íntegra. Resultados: A Universidade, por meio de seus projetos de extensão universitária voltados aos idosos tem contribuído para redução das atitudes que nutrem papéis sociais estereotipados com base na idade das pessoas. 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