Search

ABSTRACT Objective: The frequency of obstructive sleep apnea (OSA) in patients with idiopathic pulmonary fibrosis (IPF) is high. The clinical course of non-IPF interstitial lung disease (ILD) can be similar to that of IPF. We sought to assess the frequency and predictors of OSA in patients with non-IPF fibrotic ILD, as well as the impact of positive airway pressure (PAP) therapy on the quality of life of such patients. Methods: This was a prospective study in which non-IPF fibrotic ILD patients underwent a home sleep apnea test. The patients with and without OSA were compared, and a multivariate logistic regression model was used to identify independent predictors of OSA. At 3 months after initiation of PAP therapy, we evaluated the participating patients for respiratory events, nocturnal hypoxemia, and changes in quality of life. Results: Of a total of 50 patients, 50% were male, and 76% were diagnosed with OSA. The mean age was 67.8 ± 8.3 years. The patients with OSA had significantly lower TLC (p = 0.033) and awake SpO2 (p = 0.023) than did those without OSA. In the multivariate logistic regression model, SpO2 (OR = 0.46; p = 0.016) and TLC (OR = 0.95; p = 0.026) remained significantly associated with OSA risk. A total of 12 patients received PAP therapy. At 3 months after initiation of PAP therapy, 91.7% were well controlled, Epworth Sleepiness Scale scores decreased significantly (p = 0.006), and emotional well-being tended to improve (p = 0.068). PAP therapy corrected nocturnal hypoxemia in all patients. Conclusions: We found a high frequency of OSA in patients with non-IPF fibrotic ILD. A low TLC was an independent predictor of a higher risk of OSA. PAP therapy can correct nocturnal hypoxemia. There should be a low threshold for suspicion of OSA and initiation of PAP therapy in patients with non-IPF fibrotic ILD.

IntroductionThe COVID-19 pandemic disproportionately affected farmworkers in the United States and Europe, leading to increased morbidity and mortality. However, little is known about the specific impact of the pandemic on agriculture and food production workers in low- and middle-income countries. This study aimed to investigate the prevalence of SARS-CoV-2 infection and assess the mental health and economic consequences of the COVID-19 pandemic among avocado farmworkers in Michoacan, Mexico.MethodsWe conducted a cross-sectional study of adult farmworkers (n = 395) in May 2021. We collected survey data, nasal swabs and saliva samples for SARS-CoV-2 RNA detection, and blood samples for immunoglobulin G (IgG) reactivity measurements.ResultsNone of the farmworkers tested positive for SARS-CoV-2 RNA. However, among unvaccinated farmworkers (n = 336, 85%), approximately one-third (33%) showed evidence of past infection (positive for IgG against SARS-CoV-2). Unvaccinated farmworkers who lived with other farmworkers (aRR = 1.55; 95% CI: 1.05, 2.05), had ever lived with someone with COVID-19 (aRR = 1.82; 95% CI: 1.22, 2.43), and who had diabetes (aRR = 2.19; 95% CI: 1.53, 2.85) had a higher risk of testing IgG-positive for SARS-CoV-2 infection. In contrast, unvaccinated farmworkers living in more rural areas (outside of Tingambato or Uruapan) (aRR = 0.71; 95% CI: 0.46, 0.96) or cooking with wood-burning stove (aRR = 0.75; 95% CI: 0.55, 0.96) had a lower risk of IgG-positivity. Moreover, 66% of farmworkers reported a negative impact of the pandemic on their lives, 29% reported experiencing food insecurity and difficulty paying bills, and 10% reported depression or anxiety symptoms.ConclusionThe COVID-19 pandemic has significantly affected the mental health and financial well-being of avocado farmworkers. Consequently, the implementation of interventions and prevention efforts, such as providing mental health support and food assistance services, is imperative.

Summary: Background: Despite the extensive distribution of COVID-19 vaccines across Latin America, research on their real-world performance remains limited. We aimed to evaluate the effectiveness of five vaccines (BNT162b2, AZD1222, CoronaVac, Gam-COVID-Vac, and Ad5-nCoV) in a cohort of 2,559,792 pensioners covered by the Mexican Institute of Social Security. Methods: We conducted a nested test-negative design study on 28,271 individuals tested for SARS-CoV-2 infection between April and November 2021, accounting for 29,226 separate episodes. We used mixed-effects logistic regression models to estimate the vaccine effectiveness (VE) in fully vaccinated individuals for symptomatic infection, hospitalization, severe disease, and death. Findings: The median age of the study population was 70 years (interquartile range 65–76) and 76.4% (21,598/28,271) were male. VE rates were 56.3%, 75.3%, 79.7%, and 79.8% against symptomatic infection (95% confidence interval [CI]: 53.5–59.0), hospitalization (95% CI: 73.4–77.0), severe disease (95% CI: 78.0–81.3), and death (95% CI: 78.1–81.4), respectively. When evaluating vaccines individually, all showed moderate to high VE, with the best being BNT162b2 (symptomatic infection, 69.8%, 95% CI: 67.3–72.0; hospitalization, 84.1%, 95% CI: 82.5–85.6; severe disease, 88.2%, 95% CI: 86.7–89.5; and death, 88.3%, 95% CI: 86.9–89.6) and Gam-COVID-Vac (symptomatic infection, 70.0%, 95% CI: 64.8–74.4; hospitalization, 86.8%, 95% CI: 83.7–89.3; severe disease, 91.9%, 95% CI: 89.4–93.9; and death, 92.0%, 95% CI: 89.5–93.9). Interpretation: All five SARS-CoV-2 vaccines available for this population showed moderate to high levels of protection against COVID-19 and its progression to severe outcomes. Funding: Fundación IMSS, México.

This work reports the first photographic record of the Symmachia basilissa basilissa Bates, 1868 subspecies, a butterfly originally described by Henry Walter Bates in 1868. This subspecies had only been recorded three before but had never been photographed alive in Brazil. The photograph was taken in the Chapada das Mesas National Park, located in the southern part of the state of Maranhão. This record was uploaded and georeferenced on the iNaturalist app/website. The taxon Symmachia basilissa comprises four subspecies, and the article provides information on the morphological differences between them. We also discuss the use of iNaturalist and similar tools to integrate academic and citizen science for a better understanding of biodiversity, especially in tropical regions and areas that are difficult to access. Overall, our work makes a valuable contribution to the knowledge of this data deficient butterfly species and highlights the importance of utilizing new technologies and collaborative approaches to advance scientific research.

Abstract Background Although tuberculosis (TB) is a curable disease, treatment is complex and prolonged, requiring considerable commitment from patients. This study aimed to understand the common perspectives of TB patients across Brazil, Russia, India, China, and South Africa throughout their disease journey, including the emotional, psychological, and practical challenges that patients and their families face. Methods This qualitative market research study was conducted between July 2020 and February 2021. Eight TB patients from each country (n = 40) completed health questionnaires, video/telephone interviews, and diaries regarding their experiences of TB. Additionally, 52 household members were interviewed. Patients at different stages of their TB treatment journey, from a range of socioeconomic groups, with or without TB risk factors were sought. Anonymized data underwent triangulation and thematic analysis by iterative coding of statements. Results The sample included 23 men and 17 women aged 13–60 years old, with risk factors for TB reported by 23/40 patients. Although patients were from different countries and cultural backgrounds, experiencing diverse health system contexts, five themes emerged as common across the sample. 1) Economic hardship from loss of income and medical/travel expenses. 2) Widespread stigma, delaying presentation and deeply affecting patients’ emotional wellbeing. 3) TB and HIV co-infection was particularly challenging, but increased TB awareness and accelerated diagnosis. 4) Disruption to family life strained relationships and increased patients’ feelings of isolation and loneliness. 5) The COVID-19 pandemic made it easier for TB patients to keep their condition private, but disrupted access to services. Conclusions Despite disparate cultural, socio-economic, and systemic contexts across countries, TB patients experience common challenges. A robust examination of the needs of individual patients and their families is required to improve the patient experience, encourage adherence, and promote cure, given the limitations of current treatment.

Objetivo. Describir a la plataforma Cursos en Línea Masivos del IMSS (CLIMSS) como herramienta de alfabetización en salud, a través de la evaluación de la eficiencia terminal, la ganancia de competencias y satisfacción de los usuarios de cursos en línea masivos en el tema de Covid-19. Material y métodos. Se analizaron datos de 20 cursos ofertados entre marzo y octubre de 2020. Se evaluaron las calificaciones pre y pos, el número total de registros, el total de cursos terminados y la satisfacción del usuario. Resultados. Se registraron un total de 4.9 millones de usuarios y 10 millo­nes de inscripciones, en todos los estados de la República mexicana, con una eficiencia terminal de 85%, una ganancia de competencias de 30% y una satisfacción de 9.34 (10). Conclusiones. La plataforma CLIMSS ha mostrado ser una herramienta para la alfabetización en salud con un alcance de millones de mexicanos en temas relacionados con la crisis sanitaria Covid-19.

We examined respiratory disease short-term disability claims submitted to the Mexican Social Security Institute during 2020. A total of 1,631,587 claims were submitted by 19.1 million insured workers. Cumulative incidence (8.5%) was 3.6 times higher than that for January 2015‒December-2019. Workers in healthcare, social assistance, self-service, and retail stores were disproportionately affected.

Objetivo. Describir el comportamiento de la epidemia de SARS-CoV-2 entre los trabajadores afiliados al Instituto Mexicano del Seguro Social (IMSS). Material y métodos. Se analizaron las incapacidades temporales para el trabajo por enfermedades respiratorias (ITT-ER), las hospitalizaciones y defunciones asociadas durante el periodo del 1 marzo al 31 diciembre 2020. Se estimó la tasa de ataque (TA) por SARS-CoV-2, así como los riesgos relativos (RR) de ITT-ER, hos­pitalización y defunción. Resultados. De los trabajadores afiliados al IMSS, 8.8% (n=1 730 334) recibió al menos una ITT-ER. La TA fue mayor en mujeres y en ambos sexos fue menor en el grupo de >60 años. Los RR de hospitalización y defunción fueron mayores en hombres y aumentaron con la edad. Comparado con las ITT-ER de 2015-2019, Durango, Tamaulipas y Nuevo León tuvieron un RR mayor de ITT-ER que el resto del país. Conclusiones. La epidemia de SARS-CoV-2 tuvo repercusiones importantes en los trabajadores afiliados al IMSS; se observó un exceso de ITT-ER de 4.6 veces respecto a la frecuencia esperada y cerca de un millón de casos de SARS-CoV-2. Los datos sugieren que el sistema de ITT-ER puede ser utilizado como elemento adicional para la vigilancia epidemiológica de enfermedades emergentes.

Socio-demographic changes in recent decades and fire policies centered on fire suppression have substantially diminished the ability to maintain low fuel loads at the landscape scale in marginal lands. Currently, shepherds face many barriers to the use of fire for restoring pastures in shrub-encroached communities. The restrictions imposed are based on the lack of knowledge of their impacts on the landscape. We aim to contribute to this clarification. Therefore, we used a dataset of burned areas in the Alto Minho region for seasonal and unseasonal (pastoral) fires. We conducted statistical and spatial analyses to characterize the fire regime (2001–2018), the distribution of fuel types and their dynamics, and the effects of fire on such changes. Unseasonal fires are smaller and spread in different spatial contexts. Fuel types characteristic of maritime pine and eucalypts are selected by seasonal fires and avoided by unseasonal fires which, in turn, showed high preference for heterogeneous mosaics of herbaceous and shrub vegetation. The area covered by fuel types of broadleaved and eucalypt forest stands increased between 2000 and 2018 at the expense of the fuel type corresponding to maritime pine stands. Results emphasize the role of seasonal fires and fire recurrence in these changes, and the weak effect of unseasonal fires. An increase in the maritime pine fuel type was observed only in areas burned by unseasonal fires, after excluding the areas overlapping with seasonal fires.

La gestión del conocimiento se ha convertido en un tema de interés para académicos y profesionales, quienes reconocen su impacto positivo sobre el rendimiento de todo tipo de organizaciones, dentro de las que se incluyen las Instituciones de Educación Superior, sin embargo, estas presentan unas condiciones particulares que deben considerarse. Por tal razón, este artículo tiene como objetivo caracterizar la gestión del conocimiento en estas instituciones a partir de una reflexión teórica. El estudio consiste en una revisión bibliográfica de diseño cualitativo, aplicando la técnica de análisis e interpretación de contenidos a documentos de carácter científicos, hallados en diversas bases de datos. Los resultados revelan que la gestión del conocimiento es un proceso que adquiere gran relevancia para las Instituciones de Educación Superior en su esfuerzo por desarrollar exitosamente sus funciones sustantivas, no obstante, existen algunas dificultades que limitan su proceso de implementación. Para contribuir a superar estos desafíos, se propone un modelo de gestión del conocimiento compuesto por 4 fases: identificación, creación, distribución y medición; adaptado adecuadamente al funcionamiento de estas organizaciones. Se concluye que, la gestión del conocimiento es una tarea pendiente para estas, pero el modelo propuesto puede ser un punto de partida para alcanzar resultados significativos.

BackgroundCancer patients appear to be at a higher risk of complications from coronavirus disease 2019 (COVID-19). Specific data related to lung cancer (LC) patient management, active treatment, and/or recent diagnosis are still very limited. Here, we aimed to investigate the clinical presentation, baseline features, and clinical outcomes of LC patients with COVID-19.MethodsA retrospective case study was performed at Centro Hospitalar Universitário de São Joao, a tertiary hospital in the North of Portugal. Data from LC patients diagnosed with COVID-19 were collected during the first 10 months of the COVID-19 pandemic (March 2020–January 2021).ResultsTwenty-eight patients with active LC were diagnosed with COVID-19, being adenocarcinoma the most common histological type present (n = 13, 46.4%). Sixteen patients had metastatic stage IV LC (61.5%). Twenty-five patients (89.3%) had relevant comorbidities including hypertension (39.3%) and chronic obstructive pulmonary disease (32.1%). For patients undergoing antineoplastic treatment, the median time from the last chemotherapy administration to COVID-19 diagnosis was of 16 days (interquartile range = 13–41 days). Half of patients were previously on corticosteroid therapy. Twenty patients (71.4%) needed hospitalization, 18 received oxygen therapy (64.3%), 3 (10.7%) of them received high-flow nasal cannula with good tolerability, and 1 (3.6%) needed non-invasive ventilation. Hydroxychloroquine and antibiotics were given to 4 (14.3%) and 12 (42.9%) patients, respectively. Seven patients (25%) died at a median time of 5 days following COVID-19 diagnosis.ConclusionThis is one of the first studies reporting the adverse outcomes associated with COVID-19 in LC patients at same time that adds evidence regarding the need to create protocols and guidelines to reduce the infection risk in such patients.

Abstract A new species of Trypoxylon is described from females and males collected in trap-nests and Malaise traps disposed in sites of Atlantic forest in southern Brazil (Paraná and São Paulo states). Trypoxylon basirufum sp. nov. is structurally very similar to Pisoxylon roosevelti Antropov, differing in details of the color pattern, clypeal apex, male antenna and propleura. In an ongoing molecular phylogenetic study of the genus Trypoxylon, T. basirufum sp. nov. did not group with Pisoxylon amenkei Antropov, a species very close morphologically to P. xanthosoma Menke, the type species of Pisoxylon. Based on these results, the scope of the Neotropical wasp genus Pisoxylon Menke is changed to include only the type species and P. amenkei, and consequently Pisoxylon roosevelti is transferred to Trypoxylon s. str.

A new species of rockling fish genus Gaidropsarus is described based on six specimens collected in Galicia and Porcupine Banks, in Atlantic European waters. An analysis of morphological characters has confirmed the specific status of specimens of a previously described clade by comparison of DNA sequences. Gaidropsarus gallaeciae sp. nov. it is distinguished from congeners by the following combination of characters: 43–44 vertebrae; 54–60 third dorsal fin rays; 44–52 anal fin rays; 21–23 pectoral fin rays; head length 21.1–25.2% of standard length (SL); length of the pelvic fin 16.2–19% SL; length of the first dorsal fin ray 15.8–27% of head length (%HL); eye diameter 15.8–20.5% HL; and interorbital space 21.7–28% HL. Using the nucleotide sequence of the 5’ end of the mitochondrial COI gene as a molecular marker, the genetic p-distance between the new species and its congeners far exceeds the usual 2%, granting the former the status of an independent taxon, which is in accordance with the morphological identification. A comparison with the other 12 valid species of the genus is presented. The study also highlights the morphological diversity resulting from the meristic and biometric variability of Gaidropsarus species and lays the groundwork for future taxonomic studies on this genus.

Objetivo: El artículo tiene como objetivo analizar el endomarketing desde el paradigma de la sostenibilidad, mediante la elaboración de una revisión de la literatura. La relevancia que evidencia la variable como tópico de investigación de la disciplina del mercadeo en la actualidad y la necesidad de apuntar a la sostenibilidad organizacional para poder participar activa y responsablemente en el mercado, justifica la pertinencia del estudio. Método: Dentro de este marco, la investigación se presenta con un diseño cualitativo e interpretativo, de tipo documental, el cual determinó el procedimiento de selección, acceso y registro de la muestra documental, empleándose la técnica del análisis de contenido para la interpretación de los datos, privilegiando como fuente de información artículos indexados en la base de datos SCOPUS, Google Académico y Dialnet [226 artículos]. Resultados y discusión: Los resultados sugieren que el endomarketing toma relevancia en la literatura científica desde el ámbito empresarial debido a sus aportes sobre la productividad, especialmente asociado al desarrollo y motivación de los colaboradores, vinculando así el paradigma de la sostenibilidad, desde su dimensión social que persigue de la misma forma el bienestar y satisfacción del personal como respuesta a la responsabilidad de las organizaciones con sus grupos de interés. Conclusiones: En cuanto al objetivo del estudio se concluye que la implementación del endomarketing en las organizaciones contribuye al logro de los objetivos corporativos a través de la motivación del cliente interno, y al mismo tiempo, permite cubrir el compromiso social de las empresas con los trabajadores, en respuesta al enfoque de sostenibilidad que ha sido adoptado con mayor frecuencia en la actualidad.

The difficulties involved in the study of deep-sea species imply the existence of a wide gap in knowledge of this ecosystem. Here, we have obtained the mitogenome of the Oven's halosaur, Halosaurus ovenii, for the first time using low coverage Illumina Paired-end (PE) sequencing. This species belongs to order Notacanthiformes, a poorly studied group of deep-sea fishes. Moreover, given their evolutionary placement, they are critical to investigate the early diversification of the Teleostei. The assembled mitogenome displays the expected gene arrangement for vertebrate mtDNA. Phylogenetic analyses combining all the available mitogenomes of the Order Notacanthiformes were performed. The evolutionary relationships among H. ovenii and the rest of the Halosauridae family were confirmed. This mitogenome provides a valuable baseline for future research of H. ovenii.

The taxonomic identification of one Kyphosus sectatrix and two Kyphosus vaigiensis specimens caught in the European Atlantic waters of Galicia, northwestern Spain, was carried out by means of integrative taxonomy, combining the examination of morphological characters and DNA barcodes. Taxonomical assignation based on morphological characters of these specimens was tested by comparing their COI sequences with available data of Kyphosus deposited in public repositories. The resulting neighbour-joining tree defined four clades corresponding to Barcode Index Number (BIN) and indicated that some nucleotide sequences from Kyphosus, previously deposited, probably originate from misidentified specimens, as would be expected from cryptic and sympatric species. The specimens of Kyphosus vaigiensis represent a new record for the waters of Galicia and the northernmost record in the eastern Atlantic. This kind of herbivorous tropical fishes could play an important role in the tropho-dynamic context of this temperate coastal ecosystem.

Encoded Library Technology (ELT) has streamlined the identification of chemical ligands for protein targets in drug discovery. Here, the authors optimize the ELT approach to screen multiple proteins in parallel and identify promising targets and antibacterial compounds forS. aureus, A. baumannii and M. tuberculosis.

Deep-sea fish taxa are elusive, difficult to study, and in multiple cases, represent taxonomic conundrums. Here, we sequenced the complete mitogenome of the shortfin spiny eel, Notacanthus bonaparte, for the first time using low coverage Illumina Paired-end (PE) sequencing. The shortfin spiny eel belongs to the order Notacanthiformes, a relatively unknown taxon of deep-sea marine fishes mostly benthopelagic and bathydemersal. The total length of the assembled mitogenome is 16,623 bp and displays the expected gene orientation for vertebrate mtDNA. Phylogenetic analyses combining all the available mitogenomes of the order Notacanthiformes were performed. The position of N. bonaparte as a member of the Notacanthidae family was confirmed. This mitogenome provides a valuable baseline for future research of N. bonaparte.

Screens for bactericidal compounds have resulted in promising anti-tubercular hits. Here, the authors analyse in detail the target of an indazole sulfonamide (GSK3011724A), and find that it has a different mode of inhibition compared to other Kas inhibitors of fatty acid biosynthesis in bacteria.

Despite being one of the first antitubercular agents identified, isoniazid (INH) is still the most prescribed drug for prophylaxis and tuberculosis (TB) treatment and, together with rifampicin, the pillars of current chemotherapy. A high percentage of isoniazid resistance is linked to mutations in the pro-drug activating enzyme KatG, so the discovery of direct inhibitors (DI) of the enoyl-ACP reductase (InhA) has been pursued by many groups leading to the identification of different enzyme inhibitors, active against Mycobacterium tuberculosis (Mtb), but with poor physicochemical properties to be considered as preclinical candidates. Here, we present a series of InhA DI active against multidrug (MDR) and extensively (XDR) drug-resistant clinical isolates as well as in TB murine models when orally dosed that can be a promising foundation for a future treatment.

Mycobacterium phenotypic hits are a good reservoir for new chemotypes for the treatment of tuberculosis. However, the absence of defined molecular targets and modes of action could lead to failure in drug development. Therefore, a combination of ligand-based and structure-based chemogenomic approaches followed by biophysical and biochemical validation have been used to identify targets for Mycobacterium tuberculosis phenotypic hits. Our approach identified EthR and InhA as targets for several hits, with some showing dual activity against these proteins. From the 35 predicted EthR inhibitors, eight exhibited an IC50 below 50 μM against M. tuberculosis EthR and three were confirmed to be also simultaneously active against InhA. Further hit validation was performed using X-ray crystallography yielding eight new crystal structures of EthR inhibitors. Although the EthR inhibitors attain their activity against M. tuberculosis by hitting yet undefined targets, these results provide new lead compounds that could be further developed to be used to potentiate the effect of EthA activated pro-drugs, such as ethionamide, thus enhancing their bactericidal effect.

Tuberculosis is a major problem in public health. While new effective treatments to combat the disease are currently under development, they tend suffer from poor solubility often resulting in low and/or inconsistent oral bioavailability. Mesoporous materials are here investigated in an in vitro intracellular assay, for the effective delivery of compound PA-824; a poorly soluble bactericidal agent being developed against Tuberculosis (TB). Mesoporous materials enhance the solubility of PA-824; however, this is not translated into a higher antibacterial activity in TB-infected macrophages after 5 days of incubation, where similar values are obtained. The lack of improved activity may be due to insufficient release of the drug from the mesopores in the context of the cellular environment. However, these results show promising data for the use of mesoporous particles in the context of oral delivery with expected improvements in bioavailability.

Background: Photodynamic therapy (PDT) is a method of microbial reduction which can benefit periodontal treatment in areas of difficult access, such as deep pockets and furcations. The aim of this randomized controlled clinical trial was to evaluate the effects of PDT as an adjunct to full-mouth ultrasonic debridement in the treatment of severe chronic periodontitis. Material and Methods: Twenty-two patients with at least one pocket with a probing depth (PD) of ≥7 mm and one pocket with a PD of ≥5 mm and bleeding on probing (BOP) on each side of the mouth were included, characterizing a split mouth design. The control group underwent full-mouth ultrasonic debridement and the test group received the same treatment associated with PDT. The PDT was performed on only one side of the mouth and the initial step consisted of subgingival irrigation with 0.005% methylene blue dye. Two minutes after applying the photosensitizer, the low power laser – AsGaAl (Photon Lase III – PL7336, DMC, São Carlos -São Paulo, Brazil) was applied (660 nm, 100 mW, 9 J, 90 seconds per site, 320 J/cm 2 , diameter tip 600 µm). The following clinical parameters were evaluated: plaque index, gingival index, BOP, gingival recession (GR), PD, and clinical attachment level (CAL). All parameters were collected before, 1, 3 and 6 months after treatment. Results: An improvement in BOP, PD and CAL was observed after treatment, in both groups, but without any difference between them. After 6 months, the PD decreased from 5.11±0.56 mm to 2.83±0.47 mm in the test group (p

Nature Communications 8: Article number: 16081 (2017); Published: 17 July 2017, Updated: 13 July 2018 The original version of this Article omitted the following from the Acknowledgements: ‘We thank Robert Kirkpatrick for implementing the high throughput protein design strategy that enabled screeningand triage of essential A.

The main objective of this study is to review and summarize recent findings on electroencephalographic patterns in individuals with chronic pain. We also discuss recent advances in the use of quantitative Electroencephalography (qEEG) for the assessment of pathophysiology and biopsychosocial factors involved in its maintenance over time. Data collection took place from February 2014 to July 2015 in PubMed, SciELO and PEDro databases. Data from cross-sectional studies and longitudinal studies, as well as clinical trials involving chronic pain participants were incorporated into the final analysis. Our primary findings related to chronic pain were an increase of theta and alpha EEG power at rest, and a decrease in the amplitude of evoked potentials after sensory stimulation and cognitive tasks. This review suggests that qEEG could be considered as a simple and objective tool for the study of brain mechanisms involved in chronic pain, as well as for identifying the specific characteristics of chronic pain condition. In addition, results show that qEEG probably is a relevant outcome measure for assessing changes in therapeutic studies.

Notacanthiformes Goodrich, 1909 is an order of deep-sea, benthopelagic or benthic fishes distributed from the continental slope to the abyssal plain, at a depth of between 125 and 4,900 m, but mostly occurring at depths of 450-2,500 m. They are characterized by an eel-like body, a snout projecting conspicuously beyond the mouth, large connective tissue nodules inserted between the pterygoid arch and maxilla and pelvic fin webs joined in the ventral midline. Fishes from this order were classified applying DNA barcoding. Cytochrome c oxidase subunit I (COI) sequences belonging to new North Atlantic specimens and already deposited BOLD public records were used. The specimens from the two families of the order, Halosauridae (halosaurs) and Notacanthidae (spiny eels), formed separated monophyletic clades in neighbor-joining trees and the sequences clustered as coherent species. Nine out of 16 species of Halosauridae and 9 out of 10 species of Notacanthidae were represented including 166 sequences of which 96% were successfully identified. The DNA barcode of the rare species Lipogenys gillii was obtained for the first time ever. The DNA barcode was further tested by exploring the genetic structure and historical demography of four species of notacanthiforms from five sample locations of the North Atlantic and South West Pacific. Neutrality tests, mismatch distribution and haplotype networks analyses pointed to a past bottleneck episode followed by a fast demographic expansion for all the samples. The genetic structure of the abyssal halosaur Halosauropsis macrochir showed no significant differences between the North Atlantic and South West Pacific samples. DNA barcoding was successful in validating field identifications and assigning species names to sequences of notacanthiforms worldwide. These results constitute a first example of high connectivity and gene flow in this group of deep-sea fish species. The historical demography suggests population variations that may be due to past glaciation events.

The lack of success in target-based screening approaches to the discovery of antibacterial agents has led to reemergence of phenotypic screening as a successful approach of identifying bioactive, antibacterial compounds. A challenge though with this route is then to identify the molecular target(s) and mechanism of action of the hits. This target identification, or deorphanization step, is often essential in further optimization and validation studies. Direct experimental identification of the molecular target of a screening hit is often complex, precisely because the properties and specificity of the hit are not yet optimized against that target, and so many false positives are often obtained. An alternative is to use computational, predictive, approaches to hypothesize a mechanism of action, which can then be validated in a more directed and efficient manner. Specifically here we present experimental validation of an in silico prediction from a large-scale screen performed against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. The two potent anti-tubercular compounds studied in this case, belonging to the tetrahydro-1,3,5-triazin-2-amine (THT) family, were predicted and confirmed to be an inhibitor of dihydrofolate reductase (DHFR), a known essential Mtb gene, and already clinically validated as a drug target. Given the large number of similar screening data sets shared amongst the community, this in vitro validation of these target predictions gives weight to computational approaches to establish the mechanism of action (MoA) of novel screening hit.

As a follow up to the antimycobacterial screening exercise and the release of GSK´s first Tres Cantos Antimycobacterial Set (TCAMS-TB), this paper presents the results of a second antitubercular screening effort of two hundred and fifty thousand compounds recently added to the GSK collection. The compounds were further prioritized based on not only antitubercular potency but also on physicochemical characteristics. The 50 most attractive compounds were then progressed for evaluation in three different predictive computational biology algorithms based on structural similarity or GSK historical biological assay data in order to determine their possible mechanisms of action. This effort has resulted in the identification of novel compounds and their hypothesized targets that will hopefully fuel future TB drug discovery and target validation programs alike.

The human pathogen Mycobacterium tuberculosis is the causative agent of pulmonary tuberculosis (TB), a disease with high worldwide mortality rates. Current treatment programs are under significant threat from multi-drug and extensively-drug resistant strains of M. tuberculosis, and it is essential to identify new inhibitors and their targets. We generated spontaneous resistant mutants in Mycobacterium bovis BCG in the presence of 10× the minimum inhibitory concentration (MIC) of compound 1, a previously identified potent inhibitor of mycobacterial growth in culture. Whole genome sequencing of two resistant mutants revealed in one case a single nucleotide polymorphism in the gene aspS at (535)GAC>(535)AAC (D179N), while in the second mutant a single nucleotide polymorphism was identified upstream of the aspS promoter region. We probed whole cell target engagement by overexpressing either M. bovis BCG aspS or Mycobacterium smegmatis aspS, which resulted in a ten-fold and greater than ten-fold increase, respectively, of the MIC against compound 1. To analyse the impact of inhibitor 1 on M. tuberculosis AspS (Mt-AspS) activity we over-expressed, purified and characterised the kinetics of this enzyme using a robust tRNA-independent assay adapted to a high-throughput screening format. Finally, to aid hit-to-lead optimization, the crystal structure of apo M. smegmatis AspS was determined to a resolution of 2.4 Å.

Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide (THPP) and N-benzyl-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran] (Spiro) analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign. Herein, we describe the attractive in vitro and in vivo anti-tubercular profiles of both lead series. The generation of M. tuberculosis spontaneous mutants and subsequent whole genome sequencing of several resistant mutants identified single mutations in the essential mmpL3 gene. This 'genetic phenotype' was further confirmed by a 'chemical phenotype', whereby M. bovis BCG treated with both the THPP and Spiro series resulted in the accumulation of trehalose monomycolate. In vivo efficacy evaluation of two optimized THPP and Spiro leads showed how the compounds were able to reduce >2 logs bacterial cfu counts in the lungs of infected mice.

Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. Through the use of high throughput whole cell screening of an extensive compound library a number of imidazo[1,2-a]pyridine (IP) compounds were obtained as potent lead molecules active against M. tuberculosis and Mycobacterium bovis BCG. The IP inhibitors (1-4) demonstrated minimum inhibitory concentrations (MICs) in the range of 0.03 to 5 µM against a panel of M. tuberculosis strains. M. bovis BCG spontaneous resistant mutants were generated against IP 1, 3, and 4 at 5× MIC and subsequent whole genome sequencing identified a single nucleotide polymorphism (937)ACC>(937)GCC (T313A) in qcrB, which encodes the b subunit of the electron transport ubiquinol cytochrome C reductase. This mutation also conferred cross-resistance against IP 1, 3 and 4 demonstrating a common target. Gene dosage experiments confirmed M. bovis BCG QcrB as the target where over-expression in M. bovis BCG led to an increase in MIC from 0.5 to >8 µM for IP 3. An acute murine model of TB infection established bacteriostatic activity of the IP series, which await further detailed characterization.

Abstract As defined in PNSB - Law 12.334/2010 (Brasil, 2010), the DNPM, which manages the Brazilian mineral resources, is also responsible for overseeing the safety management of tailings dams in the country. The purpose of this article is to present the actions carried out in this context by the Department since the enactment of the Law in 2010, such as: elaboration of infra-legal regulatory instruments, training of civil servants, inspection actions throughout the country, seminars and lectures at mining companies and the organized civil society in general, among others, with the primary purpose of monitoring the implementation of the law instruments by mining companies, such as PSB and PAEBM, in order to avoid / mitigate accidents related to these structures.