Review of the Myelodysplastic Syndrome as a Cause of Group 5 Pulmonary Arterial Hypertension: An Orphan Disease in an Orphan Pulmonary Hypertension Group.

The coexistence of MDS and pulmonary hypertension (PH) is not a common finding and often goes unnoticed because symptoms such as dyspnea can be confused with the underlying pathology. The annual incidence of idiopathic pulmonary arterial hypertension (PAH) is only around 0.2 cases per 100,000 inhabitants, while MDS is 1 to 8 cases per 100,000 inhabitants. This review summarizes the clinical manifestations, functional respiratory tests, hemodynamic parameters using right heart catheterization, and imaging findings using echocardiography and tomography of pulmonary hypertension in myelodysplastic syndrome. We centered our discussion on the diagnosis of these patients within the hematologic disorders, especially in patients with the detriment of the functional class, as we were not used to looking for this diagnosis as a first choice. Several specialties dealing with patients with hematologic disorders (internists, hematologists, family physicians, geriatrics, oncologists) will find helpful the contents of this review.

Widespread elevated concentrations of gaseous elemental mercury in Guanajuato, Mexico, centuries after historical silver refining by mercury amalgamation.

Silver (Ag) production in Hispanic America between the 16th and 19th centuries is thought to be one of the largest sources of anthropogenic mercury (Hg) emissions in history. Recent reviews of the chemistry behind the patio process, which used Hg amalgamation to extract Ag from ore, reveal that a large amount of the Hg may not have been immediately released to the atmosphere; instead, it may have been captured in the form of calomel (Hg2Cl2, in which Hg exists as monovalent HgI) and remained in the local environment. Here we show that Hg used in the patio process centuries ago in the Guanajuato Mining District of Mexico continues to elevate present-day concentrations of gaseous elemental mercury (GEM) throughout the region. In the ground-level air, GEM ranged from 8 to 454 ng m-3, exceeding the Northern Hemispheric average (~1.4 ng m-3) by up to two orders of magnitude. Much higher concentrations, up to 44,700 ng m-3, were found in the interstitial air of reprocessed mineral wastes, sediment, and soil. These highly elevated present-day GEM values are due, at least in part, to the disproportionation of legacy calomel, as supported by the presence of HgI in the reprocessed wastes and by the GEM release pattern from calomel disproportionation. Our results imply that the contribution of historical Ag refining to atmospheric Hg emissions must be re-evaluated to account for calomel and its subsequent disproportionation and releases of GEM to the present-day.

Interplay between carbon, nitrogen and phosphate utilization in the control of secondary metabolite production in Streptomyces.

Streptomyces species are a wide and diverse source of many therapeutic agents (antimicrobials, antineoplastic and antioxidants, to name a few) and represent an important source of compounds with potential applications in medicine. The effect of nitrogen, phosphate and carbon on the production of secondary metabolites has long been observed, but it was not until recently that the molecular mechanisms on which these effects rely were ascertained. In addition to the specific macronutrient regulatory mechanisms, there is a complex network of interactions between these mechanisms influencing secondary metabolism. In this article, we review the recent advances in our understanding of the molecular mechanisms of regulation exerted by nitrogen, phosphate and carbon sources, as well as the effects of their interconnections, on the synthesis of secondary metabolites by members of the genus Streptomyces.

Carbon catabolite regulation in Streptomyces: new insights and lessons learned.

One of the most significant control mechanisms of the physiological processes in the genus Streptomyces is carbon catabolite repression (CCR). This mechanism controls the expression of genes involved in the uptake and utilization of alternative carbon sources in Streptomyces and is mostly independent of the phosphoenolpyruvate phosphotransferase system (PTS). CCR also affects morphological differentiation and the synthesis of secondary metabolites, although not all secondary metabolite genes are equally sensitive to the control by the carbon source. Even when the outcome effect of CCR in bacteria is the same, their essential mechanisms can be rather different. Although usually, glucose elicits this phenomenon, other rapidly metabolized carbon sources can also cause CCR. Multiple efforts have been put through to the understanding of the mechanism of CCR in this genus. However, a reasonable mechanism to explain the nature of this process in Streptomyces does not yet exist. Several examples of primary and secondary metabolites subject to CCR will be examined in this review. Additionally, recent advances in the metabolites and protein factors involved in the Streptomyces CCR, as well as their mechanisms will be described and discussed in this review.

Efecto de barnices fluorados sobre el esmalte erosionado a través de microscopia de fuerza atómica: Estudio in vitro / Efeitos de vernizes fluoretados em esmalte erodido mediante microscopia de força atômica: Estudo in vitro / Effect of fluoride varnishes on eroded enamel by atomic force microscopy: In vitro study

Objetivo: Evaluar el efecto de diferentes barnices fluorados sobre el esmalte erosionado a través de Microscopia de Fuerza Atómica (MFA). Materiales y métodos: Se utilizaron 30 muestras de esmalte de incisivos bovinos sin lesiones de caries defectos estructurales o fracturas, fueron divididas en 3 grupos (N=10): G1 control negativo, G2 Duraphat (Colgate) y G3 Clinpro White Varnish (3M ESPE). El MFA equipado con una punta de no contacto, con parámetros de rugosidad media (Ra) y rugosidad media cuadrática (Rrms), con imágenes de un área de 50x50 micras a una resolución de 256x256 pixeles y 0,5 Hz. Se midió la rugosidad inicial, luego se realizó desafío erosivo con Sprite Zero y remineralización con saliva artificial, después de 4 ciclos de erosión y remineralización se midió la rugosidad del esmalte como protección mecánica y al 1, 2, 3 y 4 días como protección química. Los datos se analizaron estadísticamente con las pruebas de ANOVA, Tukey y T de Student con un nivel de significancia al 5%. Resultados: El test de ANOVA mostró una diferencia en los grupos de barnices de flúor en el 2º, 3º y 4º día en comparación con el grupo control (p <0,05). El test de Tukey mostró una diferencia entre Duraphat y Clinpro en valores de Ra (p = 0,03) y Rrms (p = 0,05) en el 4°día. La T de Student demostró que no hay diferencias para Clinpro en Ra (p = 0,14) y Rrms (p = 0,13) desde los valores iniciales hasta el 4º día. Conclusión: Clinpro White Varnish tiene una mejor acción para reducir la rugosidad superficial en la superficie del esmalte cuando se somete a desafíos ácidos.

Purpose: To evaluate the effect of different fluoride varnishes on eroded enamel through Atomic Force Microscopy (AFM). Materials and Methods: 30 samples of bovine incisor enamel without carious lesions, defective structure or fractures were divided into 3 groups (N = 10): G1: negative control, G2: Duraphat® (Colgate) and G3: Clinpro™ White Varnish (3M ESPE). The AFM was used, equipped with a non-contact tip with parameters such as average roughness (Ra) and the mean square roughness (Rrms) at an area for images of 50 x 50 microns with a resolution of 256 X 256 pixels and 0.5 Hz. First, the initial roughness was measured, then an erosive trail was carried out with Sprite Zero and remineralization with artifi-cial saliva. After 4 cycles of erosion and remineralization, the roughness of enamel as mechanic protection was measured and at 1, 2, 3 and 4 days as chemical protection. Data were analyzed statistically with ANOVA, Tukey and Student T with a significance level of 5%. Results: The ANOVA test showed a difference in the groups of fluoride varnishes on the 2nd, 3rdand 4th day in comparison with the control group (p <0.05). The Tukey test showed a difference between Duraphat® and Clinpro™ in the values of Ra (p = 0.03) and Rrms (p = 0.05) on the 4th day. The Student's T test showed no difference for Clinpro™ in Ra (p = 0.14) and Rrms (0.13) from the initial values until 4th day. Conclusion: Clinpro™ White Varnish shows better results to reduce surface roughness in the enamel when subjected to acidic trails.

Objetivo: Avaliar o efeito de diferentes vernizes fluoretados no esmalte erodido por meio de microscopia de força atômica (MFA). Materiais e Métodos: Foram selecionadas 30 amostras de esmalte de incisivos bovinos sem cárie, defeitos de estrutura ou fraturas, foram divididas em 3 grupos (n = 10): G1: controle negativo, G2: Duraphat (Colgate) e G3: Clinpro White Varnish (3M ESPE). Foi utilizado MFA, equipado com uma ponta de não contato. Determinaram-se parâmetros fotográficos como a rugosidade média (Ra) e rugosidade média quadrática (Rrms) da superfície, com imagens de uma área de 50 x 50 microns com uma resolução de 256 X 256 pixels e 0,5 Hz. Em primeiro lugar procedeu-se realizar a medição da rugosidade inicial, foi realizada o desafio erosivo com Sprite Zero e remineralização com saliva artificial, após 4 ciclos de erosão e remineralização foi medido a rugosidade do esmalte foi medida como proteção mecânica e ao 1, 2, 3 e 4 dias como proteção química. Os dados foram analisados estatisticamente com ANOVA, Tukey T de Student com um nível de significância de 5%. Resultados: O Teste de ANOVA mostrou uma diferença dos grupos de vernizes fluoretados no 2º, 3º e 4º dia em comparação com o grupo controle (p <0,05). O Teste de Tukey mostrou uma diferença entre Duraphat e Clinpro nos valores de Ra (p = 0,03) e Rrms ao 4° dia (p = 0,05). O teste T de Student não mostrou nenhuma diferença para Clinpro em Ra (p = 0,14) e Rrms (0,13) dos valores iniciais até ao dia 4. Conclusão: O Verniz Clinpro White Varnish tem melhor ação na redução da rugosidade da superfície do esmalte quando foi submetido à desafios ácidos.

Transcriptomic analysis of a classical model of carbon catabolite regulation in Streptomyces coelicolor.

BACKGROUND: In the genus Streptomyces, one of the most remarkable control mechanisms of physiological processes is carbon catabolite repression (CCR). This mechanism regulates the expression of genes involved in the uptake and utilization of alternative carbon sources. CCR also affects the synthesis of secondary metabolites and morphological differentiation. Even when the outcome effect of CCR in different bacteria is the same, their essential mechanisms can be quite different. In several streptomycetes glucose kinase (Glk) represents the main glucose phosphorylating enzyme and has been regarded as a regulatory protein in CCR. To evaluate the paradigmatic model proposed for CCR in Streptomyces, a high-density microarray approach was applied to Streptomyces coelicolor M145, under repressed and non-repressed conditions. The transcriptomic study was extended to assess the ScGlk role in this model by comparing the transcriptomic profile of S. coelicolor M145 with that of a ∆glk mutant derived from the wild-type strain, complemented with a heterologous glk gene from Zymomonas mobilis (Zmglk), insensitive to CCR but able to grow in glucose (ScoZm strain). RESULTS: Microarray experiments revealed that glucose influenced the expression of 651 genes. Interestingly, even when the ScGlk protein does not have DNA binding domains and the glycolytic flux was restored by a heterologous glucokinase, the ScGlk replacement modified the expression of 134 genes. From these, 91 were also affected by glucose while 43 appeared to be under the control of ScGlk. This work identified the expression of S. coelicolor genes involved in primary metabolism that were influenced by glucose and/or ScGlk. Aside from describing the metabolic pathways influenced by glucose and/or ScGlk, several unexplored transcriptional regulators involved in the CCR mechanism were disclosed. CONCLUSIONS: The transcriptome of a classical model of CCR was studied in S. coelicolor to differentiate between the effects due to glucose or ScGlk in this regulatory mechanism. Glucose elicited important metabolic and transcriptional changes in this microorganism. While its entry and flow through glycolysis and pentose phosphate pathway were stimulated, the gluconeogenesis was inhibited. Glucose also triggered the CCR by repressing transporter systems and the transcription of enzymes required for secondary carbon sources utilization. Our results confirm and update the agar model of the CCR in Streptomyces and its dependence on the ScGlk per se. Surprisingly, the expected regulatory function of ScGlk was not found to be as global as thought before (only 43 out of 779 genes were affected), although may be accompanied or coordinated by other transcriptional regulators. Aside from describing the metabolic pathways influenced by glucose and/or ScGlk, several unexplored transcriptional regulators involved in the CCR mechanism were disclosed. These findings offer new opportunities to study and understand the CCR in S. coelicolor by increasing the number of known glucose and ScGlk -regulated pathways and a new set of putative regulatory proteins possibly involved or controlling the CCR.

Nasalância na presença e ausência da fricativa faríngea / Nasalance at presence and absence of pharyngeal fricative

RESUMO Objetivo: comparar os valores de nasalância em amostras de fala com e sem o uso de fricativa faríngea e, também, com e sem hipernasalidade. Métodos: um total de 840 amostras de fala foi analisado neste estudo. As amostras foram julgadas por três juízas experientes por consenso quanto aos aspectos hipernasalidade e fricativa faríngea. Os julgamentos foram distribuídos em quatro grupos: G1: 255 amostras de fala julgadas como representativas de hipernasalidade; G2: 130 amostras julgadas como representativas do uso de fricativa faríngea e hipernasalidade; G3: 280 amostras julgadas como representativas de fala normal em falantes com história de fissura labiopalatina; G4: 175 amostras julgadas como representativas de fala normal em falantes sem história de fissura labiopalatina. Para análise dos dados foi utilizando o teste Kruskal-Wallis e quando houve diferença estatisticamente significante foi aplicado o teste Dunn's para comparar os grupos aos pares. Resultados: os julgamentos aferidos por consenso pelas três juízas permitiram a identificação de amostras representativas do uso de fricativa faríngea e da presença e ausência de hipernasalidade. Foram estabelecidos valores de nasalância (média e desvio padrão) para cada grupo e observou-se que houve diferença estatisticamente significante entre os grupos com alteração de fala (G1 e G2) e aqueles sem alteração (G3 e G4). A diferença entre o grupo com hipernasalidade (G1) e o grupo com FF (G2) não foi significante. Conclusão: o uso de FF não influenciou significantemente os valores de nasalância para a amostra estudada.

ABSTRACT Purpose: to compare nasalance scores between speech samples with and without pharyngeal fricative and with and without hypernasality. Methods: a total of 840 speech samples was analyzed in this study. The samples were rated by three experienced judges with consensus regarding the aspects of hypernasality and pharyngeal fricative. The ratings were distributed into 4 groups: G1: 255 samples rated as representative of presence of hypernasality; G2: 130 samples rated as representative of use of pharyngeal fricative and hypernasality; G3: 280 samples rated as representative of normal speech for speakers with history of cleft palate; G4: 175 samples rated as representative of normal speech for speakers without history of cleft palate. Statistical analysis involved the Kruskal-Wallis test and when significant the Dunn's test was used to compared pairs of data. Results: the ratings established with agreement between the 3 experienced judges allowed for the identification of the samples representative of use of pharyngeal fricative and hypernasal speech. Nasalance scores were establish for each group revealing a significant difference between groups G1+G2 (representative of speech errors) and groups G3+G4 (representative of normal speech). The difference between the group with hypernasality (G1) and the group with pharyngeal fricative (G2) was not significant. Conclusion: the use of pharyngeal fricative did not influence significantly the nasalance values obtained for the studied sample.

Teletrabajo y su relación con la seguridad y salud en el trabajo / Telework and its relationship with health and safety at work

El teletrabajo es una modalidad laboral que está siendo promovida e implementada en Colombia como estrategia de generación de empleo. Sin embargo, esta forma de flexibilización del trabajo exige que se den unas garantías mínimas en materia de protección a los trabajadores. Por tal razón, el presente artículo busca mostrar cuáles han sido los avances en investigación del teletrabajo, particularmente en lo relacionado con la seguridad y salud en el trabajo. Para este propósito se realizó una revisión de estudios en diferentes bases de datos y revistas científicas indexadas. Como resultado se identificaron aspectos como la ampliación del mercado laboral, flexibilidad laboral, inclusión de la población en situación de discapacidad a la vida laboral y conciliación con la vida familiar. Sin embargo, se encontró que en cuanto a la salud de los teletrabajadores y sus riesgos, son las empresas quienes los asumen en la mayoría de los casos. Por otra parte, se observó que falta regulación legal y jurídica para la implementación del teletrabajo en muchos de los países donde se realizaron las investigaciones y estudios. En conclusión, se hace necesario determinar aspectos contractuales, responsabilidades de las empresas, definición de horarios y tiempos de trabajo, condiciones de salud y seguridad, vigilancia, acompañamiento, necesidad de crear capacitaciones específicas para el teletrabajador y las empresas que tengan esta modalidad.

This article shows the results obtained according to telework and its relation to health and safety, building cataloging objectives studies have been performed to identify the achievements obtained in the different studies and research and categorize them according to the evidence found. In different databases and scientific journals a review of studies and research was conducted, which were related to the main theme. As a result were identified issues such as the expansion of the labor market, labor flexibility, inclusion of people with disabilities in working life, family life reconciliation. However, it was found that in terms of the health of teleworkers and their risks are the companies who take in most cases. On the other hand, lack of legal and judicial regulation for the implementation of teleworking in many of the countries where the research and studies conducted. It is necessary to determine contractual, corporate responsibilities, defining work schedules and time, health and safety conditions, monitoring, need for specific training for teleworkers and companies with this modality.

Interaction of SCO2127 with BldKB and its possible connection to carbon catabolite regulation of morphological differentiation in Streptomyces coelicolor.

In Streptomyces coelicolor, the sco2127 gene is located upstream of the gene encoding for glucose kinase. This region restores sensitivity to carbon catabolite repression (CCR) of Streptomyces peucetius var. caesius mutants, resistant to 2-deoxyglucose (Dog(R)). In order to search for the possible mechanisms behind this effect, sco2127 was overexpressed and purified for protein-protein interaction studies. SCO2127 was detected during the late growth phase of S. coelicolor grown in a complex media supplemented with 100 mM glucose. Pull-down assays using crude extracts from S. coelicolor grown in the same media, followed by far-western blotting, allowed detection of two proteins bound to SCO2127. The proteins were identified by MALDI-TOF mass spectrometry as SCO5113 and SCO2582. SCO5113 (BldKB) is a lipoprotein ABC-type permease (∼66 kDa) involved in mycelium differentiation by allowing the transport of the morphogenic oligopeptide Bld261. SCO2582, is a putative membrane metalloendopeptidase (∼44 kDa) of unknown function. In agreement with the possible role of SCO2127 in mycelium differentiation, delayed aerial mycelium septation and sporulation was observed when S. coelicolor A3(2) was grown in the presence of elevated glucose concentrations (100 mM), an effect not seen in a Δ-sco2127 mutant derived from it. We speculate that SCO2127 might represent a key factor in CCR of mycelium differentiation by interacting with BldKB.

S-allylcysteine scavenges singlet oxygen and hypochlorous acid and protects LLC-PK(1) cells of potassium dichromate-induced toxicity.

It has been found that S-allylcysteine (SAC), a garlic-derived compound, has in vivo and in vitro antioxidant properties. In addition, it is known that SAC is able to scavenge different reactive oxygen or nitrogen species including superoxide anion (O(2)(-)), hydrogen peroxide (H(2)O(2)), hydroxyl radical (OH()), and peroxynitrite anion (ONOO(-)) although the IC(5O) values for each reactive species has not been calculated and the potential ability of SAC to scavenge singlet oxygen ((1)O(2)) and hypochlorous acid (HOCl) has not been explored. The purposes of this work was (a) to explore the potential ability of SAC to scavenge (1)O(2) and HOCl, (b) to further characterize the O(2)(-), H(2)O(2), OH(), and ONOO(-) scavenging ability of SAC by measuring the IC(50) values using in vitro assays, and (c) to explore the potential ability of SAC to ameliorate the potassium dichromate (K(2)Cr(2)O(7))-induced cytotoxicity in LLC-PK1 cells in which oxidative stress is involved. The scavenging activity was compared against the following reference compounds: N-acetylcysteine for O(2)(-), sodium pyruvate for H(2)O(2), dimethylthiourea for OH(), lipoic acid and glutathione for (1)O(2), lipoic acid for HOCl, and penicillamine for ONOO(-). It was found that SAC was able to scavenge concentration-dependently all the species assayed with the following IC(5O) (mean+/-SEM, mM): O(2)(-) (14.49+/-1.67), H(2)O(2) (68+/-1.92), OH() (0.68+/-0.06), (1)O(2) (1.93+/-0.27), HOCl (2.86+/-0.15), and ONOO(-) (0.80+/-0.05). When the ability of SAC to scavenge these species was compared to those of the reference compounds it was found that the efficacy of SAC (a) to scavenge O(2)(-), H(2)O(2), OH(), and ONOO(-) was lower, (b) to scavenge HOCl was similar, and (c) to scavenge (1)O(2) was higher. In addition, it was found that SAC was able to prevent K(2)Cr(2)O(7)-induced toxicity in LLC-PK1 cells in culture. It was showed for the first time that SAC is able to scavenge (1)O(2) and HOCl and to ameliorate the K(2)Cr(2)O(7)-induced toxicity.