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BACKGROUND: The Peruvian 'chanque' or Chilean 'loco' Concholepas concholepas is an economically, ecologically, and culturally important muricid gastropod heavily exploited by artisanal fisheries in the temperate southeastern Pacific Ocean. In this study, we have profited from a set of bioinformatics tools to recover important biological information of C. concholepas from low-coverage short-read NGS datasets. Specifically, we calculated the size of the nuclear genome, ploidy, and estimated transposable elements content using an in silico k-mer approach, we discovered, annotated, and quantified those transposable elements, we assembled and annotated the 45S rDNA RNA operon and mitochondrial genome, and we confirmed the phylogenetic position of C. concholepas within the muricid subfamily Rapaninae based on translated protein coding genes. RESULTS: Using a k-mer approach, the haploid genome size estimated for the predicted diploid genome of C. concholepas varied between 1.83 Gbp (with kmer = 24) and 2.32 Gbp (with kmer = 36). Between half and two thirds of the nuclear genome of C. concholepas was composed of transposable elements. The most common transposable elements were classified as Long Interspersed Nuclear Elements and Short Interspersed Nuclear Elements, which were more abundant than DNA transposons, simple repeats, and Long Terminal Repeats. Less abundant repeat elements included Helitron mobile elements, 45S rRNA DNA, and Satellite DNA, among a few others.The 45S rRNA DNA operon of C. concholepas that encodes for the ssrRNA, 5.8S rRNA, and lsrRNA genes was assembled into a single contig 8,090 bp long. The assembled mitochondrial genome of C. concholepas is 15,449 bp long and encodes 13 protein coding genes, two ribosomal genes, and 22 transfer RNAs. CONCLUSION: The information gained by this study will inform the assembly of a high quality nuclear genome for C. concholepas and will support bioprospecting and biomonitoring using environmental DNA to advance development of conservation and management plans in this overexploited marine snail.
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Gastrópodes , Genoma Mitocondrial , Animais , Gastrópodes/genética , Gastrópodes/metabolismo , Elementos de DNA Transponíveis/genética , Tamanho do Genoma , Filogenia , RNA Nuclear/metabolismo , Caramujos/genética , Óperon , PloidiasRESUMO
To assess the possible interactions between the dorsolateral periaqueductal gray matter (dlPAG) and the different domains of the nucleus ambiguus (nA), we have examined the pattern of double-staining c-Fos/FoxP2 protein immunoreactivity (c-Fos-ir/FoxP2-ir) and tyrosine hydroxylase (TH) throughout the rostrocaudal extent of nA in spontaneously breathing anaesthetised male Sprague-Dawley rats during dlPAG electrical stimulation. Activation of the dlPAG elicited a selective increase in c-Fos-ir with an ipsilateral predominance in the somatas of the loose (p < 0.05) and compact formation (p < 0.01) within the nA and confirmed the expression of FoxP2 bilaterally in all the domains within the nA. A second group of experiments was made to examine the importance of the dlPAG in modulating the laryngeal response evoked after electrical or chemical (glutamate) dlPAG stimulations. Both electrical and chemical stimulations evoked a significant decrease in laryngeal resistance (subglottal pressure) (p < 0.001) accompanied with an increase in respiratory rate together with a pressor and tachycardic response. The results of our study contribute to new data on the role of the mesencephalic neuronal circuits in the control mechanisms of subglottic pressure and laryngeal activity.
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Estimulação Elétrica , Laringe , Substância Cinzenta Periaquedutal , Proteínas Proto-Oncogênicas c-fos , Ratos Sprague-Dawley , Animais , Masculino , Ratos , Substância Cinzenta Periaquedutal/metabolismo , Substância Cinzenta Periaquedutal/fisiologia , Estimulação Elétrica/métodos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Laringe/fisiologia , Laringe/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , Pressão , Bulbo/metabolismo , Bulbo/fisiologia , Ácido Glutâmico/metabolismoRESUMO
The search for long molecular wires that can transport charge with maximum efficiency over many nanometers has driven molecular electronics since its inception. Single-molecule conductance normally decays with length and is typically far below the theoretical limit of G0 (77.5 µS). Here, we measure the conductances of a family of edge-fused porphyrin ribbons (lengths 1-7 nm) that display remarkable behavior. The low-bias conductance is high across the whole series. Charging the molecules in situ results in a dramatic realignment of the frontier orbitals, increasing the conductance to 1 G0 (corresponding to a current of 20 µA). This behavior is most pronounced in the longer molecules due to their smaller HOMO-LUMO gaps. The conductance-voltage traces frequently exhibit peaks at zero bias, showing that a molecular energy level is in resonance with the Fermi level. This work lays the foundations for long, perfectly transmissive, molecular wires with technological potential.
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BACKGROUND: Neoadjuvant dabrafenib plus trametinib has a high pathological response rate and impressive short-term survival in patients with resectable stage III melanoma. We report 5-year outcomes from the phase II NeoCombi trial. PATIENTS AND METHODS: NeoCombi (NCT01972347) was a single-arm, open-label, single-centre, phase II trial. Eligible patients were adults (aged ≥18 years) with histologically confirmed, resectable, RECIST-measurable, American Joint Committee on Cancer seventh edition clinical stage IIIB-C BRAF V600E/K-mutant melanoma and Eastern Cooperative Oncology Group performance status ≤1. Patients received 52 weeks of treatment with dabrafenib 150 mg (orally twice per day) plus trametinib 2 mg (orally once per day), with complete resection of the pre-therapy tumour bed at week 12. RESULTS: Between 20 August 2014 and 19 April 2017, 35 patients were enrolled. At data cut-off (17 August 2021), the median follow-up was 60 months [95% confidence interval (CI) 56-72 months]. Overall, 21 of 35 (60%) patients recurred, including 12 (57%) with first recurrence in locoregional sites (followed by later distant recurrence in 6) and 9 (43%) with first recurrence in distant sites, including 3 in the brain. Most recurrences occurred within 2 years, with no recurrences beyond 3 years. At 5 years, recurrence-free survival (RFS) was 40% (95% CI 27% to 60%), distant metastasis-free survival (DMFS) was 57% (95% CI 42% to 76%), and overall survival was 80% (95% CI 67% to 94%). Five-year survival outcomes were stratified by pathological response: RFS was 53% with pathological complete response (pCR) versus 28% with non-pCR (P = 0.087), DMFS was 59% versus 55% (P = 0.647), and overall survival was 88% versus 71% (P = 0.205), respectively. CONCLUSIONS: Neoadjuvant dabrafenib plus trametinib has high pathological response rates in clinical stage III melanoma, but low rates of RFS, similar to those achieved with adjuvant targeted therapy alone. Patients with a pCR to dabrafenib plus trametinib still had a high risk of recurrence, unlike that seen with immunotherapy where recurrences are rare.
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Protocolos de Quimioterapia Combinada Antineoplásica , Imidazóis , Melanoma , Terapia Neoadjuvante , Estadiamento de Neoplasias , Oximas , Piridonas , Pirimidinonas , Humanos , Oximas/administração & dosagem , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/mortalidade , Pirimidinonas/administração & dosagem , Piridonas/administração & dosagem , Imidazóis/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Adulto , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/mortalidade , SeguimentosRESUMO
The purpose of this study was to analyze and molecularly describe the largest group of patients with ABCA4-associated retinal degeneration in Latin America. Pathogenic variants in ABCA4, a member of the ATP Binding Cassette (ABC) transporters superfamily, is one of the most common causes of inherited visual deficiency in humans. Retinal phenotypes associated with genetic defects in ABCA4 are collectively known as ABCA4-associated retinal degenerations (ABCA4R), a group of recessively inherited disorders associated with a high allelic heterogeneity. While large groups of Caucasian and Asiatic individuals suffering from ABCA4R have been well characterized, molecular information from certain ethnic groups is limited or unavailable, precluding a more realistic knowledge of ABCA4-related mutational profile worldwide. In this study, we describe the molecular findings of a large group of 211 ABCA4R index cases from Mexico. Genotyping was performed using either next generation sequencing (NGS) of a retinal dystrophy genes panel or exome. ABCA4 targeted mutation testing was applied to a subgroup of subjects in whom founder mutations were suspected. A total of 128 different ABCA4 pathogenic variants were identified, including 22 previously unpublished variants. The most common type of genetic variation was single nucleotide substitutions which occurred in 92.7% (408/440 alleles). According to the predicted protein effect, the most frequent variant type was missense, occurring in 83.5% of disease-causing alleles (368/440). Mutations such as p.Ala1773Val are fully demonstrated as a founder effect in native inhabitants of certain regions of Mexico. This study also gives us certain indications of other founder effects that need to be further studied in the near future. This is the largest molecularly characterized ABCA4R Latin American cohort, and our results supports the value of conducting genetic screening in underrepresented populations for a better knowledge of the mutational profile leading to monogenic diseases.
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Transportadores de Cassetes de Ligação de ATP , Genótipo , Degeneração Retiniana , Humanos , Transportadores de Cassetes de Ligação de ATP/genética , México , Masculino , Feminino , Degeneração Retiniana/genética , Criança , Mutação , Adulto , Adolescente , Pessoa de Meia-Idade , Sequenciamento de Nucleotídeos em Larga Escala , Alelos , Fenótipo , Pré-Escolar , Adulto Jovem , LinhagemRESUMO
Antiaromaticity is a fundamental concept in chemistry, but the study of molecular wires incorporating antiaromatic units is limited. Despite initial predictions, very few studies show that antiaromaticity has a beneficial effect on electron transport. Dibenzo[a,e]pentalene (DBP) is a stable structure that displays appreciable antiaromaticity within the five-membered rings of the pentalene core. We have investigated derivatives of DBP furnished with pyridyl (Py) and F4-pyridyl (PyF4) anchor groups, and compared the conductance with purely aromatic phenyl and anthracene analogues. We find that the low-bias conductance of DBP-Py is approximately 60 % larger than that of the anthracene analogue Anth-Py and 250 % larger compared to the phenyl derivative Ph-Py. This is due to a better alignment of the LUMO with the gold Fermi level, which we confirm by conductance-voltage spectroscopy where the conductance of DBP-Py shows the greatest voltage-dependence. The F4-pyridyl compounds, which have lower LUMO energies compared to the pyridyl analogues, did not, however, form detectable molecular junctions. The strongly electron-withdrawing fluorine atoms reduce the donor capability of the nitrogen lone-pair to the point where stable N-Au bonds no longer form.
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Over the last years metal halide perovskites have demonstrated remarkable potential for integration in light emitting devices. Heterostructures allow for tunable bandgap depending on the local anion composition, crucial for optoelectronic devices, but local structural effects of anion exchange in single crystals is not fully understood. Here, we investigate how the anion exchange of CsPbBr3nanowires fully and locally exposed to HCl vapor affects the local crystal structure, using nanofocused x-rays. We study the nanoscale composition and crystal structure as function of HCl exposure time and demonstrate the correlation of anion exchange with changes in the lattice parameter. The local composition was measured by x-ray fluorescence and x-ray diffraction, with general agreement of both methods but with much less variation using latter. The heterostructured nanowires exhibit unintentional gradients in composition, both axially and radially. Ferroelastic domains are observed for all HCl exposure times, and the magnitude of the lattice tilt at the domain walls scales with the Cl concentration.
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PURPOSE: The quality, rather than the quantity, of carbohydrate intake may play a major role in the etiology of obesity-related cancers (ORCs). We assessed the association between a previously defined carbohydrate quality index (CQI) and the risk of developing ORCs in the "Seguimiento Universidad de Navarra" (SUN) cohort. METHODS: A total of 18,446 Spanish university graduates [mean age 38 years (SD 12 years), 61% women, mean BMI 23.5 kg/m2 (SD 3.5 kg/m2)], with no personal history of cancer, were followed-up. Baseline CQI was assessed summing quintiles of four previously defined criteria: high dietary fiber intake, low glycemic index (GI), high whole-grain: total-grain carbohydrates ratio and high solid carbohydrates: total carbohydrates ratio. Participants were classified into tertiles of their total CQI. Incident ORCs were confirmed by an oncologist using medical records and by querying the National Death Index blindly to dietary exposures. RESULTS: During a median follow-up of 13.7 years, 269 incident cases of ORC were confirmed. A higher CQI was inversely associated with ORC incidence [multivariable-adjusted hazard ratio (HR) for the upper (T3) versus the lowest tertile (T1) of 0.68 (95% CI: 0.47-0.96), p for trend = 0.047]. Particularly, higher dietary fiber intake was inversely associated with ORC, HRT3 vs. T1=0.57 (95% CI 0.37-0.88 p for trend = 0.013). CONCLUSION: In this prospective Mediterranean cohort, an inverse association between a better global quality of carbohydrate intake and the risk of ORCs was found. Strategies for cancer prevention should promote a higher quality of carbohydrate intake.
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SS 433 is a binary system containing a supergiant star that is overflowing its Roche lobe with matter accreting onto a compact object (either a black hole or neutron star)1-3. Two jets of ionized matter with a bulk velocity of approximately 0.26c (where c is the speed of light in vacuum) extend from the binary, perpendicular to the line of sight, and terminate inside W50, a supernova remnant that is being distorted by the jets2,4-8. SS 433 differs from other microquasars (small-scale versions of quasars that are present within our own Galaxy) in that the accretion is believed to be super-Eddington9-11, and the luminosity of the system is about 1040 ergs per second2,9,12,13. The lobes of W50 in which the jets terminate, about 40 parsecs from the central source, are expected to accelerate charged particles, and indeed radio and X-ray emission consistent with electron synchrotron emission in a magnetic field have been observed14-16. At higher energies (greater than 100 gigaelectronvolts), the particle fluxes of γ-rays from X-ray hotspots around SS 433 have been reported as flux upper limits6,17-20. In this energy regime, it has been unclear whether the emission is dominated by electrons that are interacting with photons from the cosmic microwave background through inverse-Compton scattering or by protons that are interacting with the ambient gas. Here we report teraelectronvolt γ-ray observations of the SS 433/W50 system that spatially resolve the lobes. The teraelectronvolt emission is localized to structures in the lobes, far from the centre of the system where the jets are formed. We have measured photon energies of at least 25 teraelectronvolts, and these are certainly not Doppler-boosted, because of the viewing geometry. We conclude that the emission-from radio to teraelectronvolt energies-is consistent with a single population of electrons with energies extending to at least hundreds of teraelectronvolts in a magnetic field of about 16 microgauss.
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In this Letter, owing to a production error, the penultimate version of the PDF was published. The HTML version was always correct. The PDF has been corrected online.
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Barnard's star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs1, it is the closest single star to the Sun; only the three stars in the α Centauri system are closer. Barnard's star is also among the least magnetically active red dwarfs known2,3 and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging4-6, astrometry7,8 and direct imaging9, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard's star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard's star, making it an excellent target for direct imaging and astrometric observations in the future.
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OBJECTIVE: To examine the relationship between the age-adjusted Charlson comorbidity index (A-CCI) with body composition and overall survival in patients newly diagnosed with colorectal cancer (CRC). RESEARCH METHODS AND PROCEDURES: In this cohort study, patients (≥ 18 years old) with CRC were followed for 36 months. Computed tomography images of the third lumbar were analyzed to determine body composition, including skeletal muscle area (SMA), skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Phenotypes based on comorbidity burden assessed by A-CCI and body composition parameters were established. RESULTS: A total of 436 participants were included, 50% male, with a mean age of 61 ± 13.2 years. Approximately half of the patients (50.4%) had no comorbidity, and the A-CCI median score was 4 (interquartile range: 3-6). A higher A-CCI score was a risk factor for 36-month mortality (HR = 3.59, 95% CI = 2.17-5.95). Low SMA and low SMD were associated with a higher A-CCI. All abnormal phenotypes (high A-CCI and low SMA; high A-CCI and low SMD; high A-CCI and high VAT) were independently associated with higher 36-month mortality hazard (adjusted HR 5.12, 95% CI 2.73-9.57; adjusted HR 4.58, 95% CI 2.37-8.85; and adjusted HR 2.36, 95% CI 1.07-5.22, respectively). CONCLUSION: The coexistence of comorbidity burden and abnormal body composition phenotypes, such as alterations in muscle or fat compartments, may pose an additional risk of mortality in patients newly diagnosed with CRC. Early assessment and management of these phenotypes could be crucial in optimizing outcomes in such patients.
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Composição Corporal , Neoplasias Colorretais , Comorbidade , Humanos , Masculino , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Pessoa de Meia-Idade , Feminino , Idoso , Estudos de Coortes , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos , Fatores EtáriosRESUMO
PURPOSE: Vitamin D deficiency has been associated with multiple chronic diseases, including metabolic disorders such as insulin resistance and type 2 diabetes (T2D). The aim of the study was to analyze the association between validated predicted serum vitamin D status and the risk of developing T2D in a large prospective cohort based on a Mediterranean population. METHODS: The SUN project is a prospective and dynamic Spanish cohort that gathers university graduates who have answered lifestyle questionnaires, including a validated Food Frequency Questionnaire. The association between predicted serum vitamin D and the risk of T2D was assessed through Cox regression models according to quartiles (Q) of predicted vitamin D at baseline. The models were adjusted for potential confounders and sensitivity analyses were performed to ensure the robustness of our findings. RESULTS: Our study included a total of 18,594 participants and after a total follow-up of 238,078 person-years (median follow-up of 13.5 years), 209 individuals were diagnosed with incident T2D. We found a significant inverse association between predicted levels of serum vitamin D and the risk of developing T2D, after adjusting for potential confounders and performing different sensitivity analyses (hazard ratio Q4 vs. Q1: 0.48, 95% CI 0.26-0.88; p for trend = 0.032). CONCLUSION: The outcomes suggest that higher levels of vitamin D at baseline may be associated with a reduced risk of developing T2D.
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Diabetes Mellitus Tipo 2 , Deficiência de Vitamina D , Vitamina D , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Estudos Prospectivos , Masculino , Feminino , Vitamina D/sangue , Pessoa de Meia-Idade , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Adulto , Fatores de Risco , Seguimentos , Espanha/epidemiologia , IncidênciaRESUMO
This chapter analyses the taxonomic position of the Dicrocoeliidae family and several of its genera and species. The chapter reviews the biology of major veterinary disease-causing species, including Dicrocoelium dendriticum, Dicrocoelium hospes, Dicrocoelium chinensis, Eurytrema pancreaticum and Platynosomum fastosum. All these species have indirect life cycles with two intermediate hosts: molluscs as the first host and ants, grasshoppers and lizards as the second host. Dicrocoelium dendriticum is a widespread liver fluke found in ruminants across Europe, Asia, North Africa and North America. It can also infect humans. Dicrocoelium hospes is widely distributed in the savanna areas of Africa south of the Sahara, while D. chinensis is mainly found in ruminants in East Asia and some European countries (probably imported from Asia). Eurytrema pancreaticum is a common parasite that lives in the bile ducts, gall bladder, pancreatic ducts and intestines of ruminants. It is found in Europe, Madagascar, Asia and South America. Adults of P. fastosum live in the liver, gall bladder and pancreas of birds and mammals in Europe, Africa, Asia, North, Central and South America. Information on the epidemiology, pathology, clinical aspects, diagnosis, treatment, control, prevention and economic impact of Dicrocoeliosis caused by D. dendriticum, Eurytrematodosis and Platynosomiosis have been included.
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Dicrocoeliidae , Animais , Dicrocoeliidae/genética , Dicrocoeliidae/patogenicidade , Dicrocelíase/epidemiologia , Dicrocelíase/diagnóstico , Dicrocelíase/veterinária , Dicrocelíase/parasitologia , HumanosRESUMO
PURPOSE: To describe a novel endoscopic technique to approach the maxillary sinus (MS), the Modified Anterior Medial Maxillary Approach (MAMMA), preserving the inferior turbinate (IT) and the nasolacrimal duct (NLD). To perform radiological measurements and describe a case series to study the feasibility and limits of MAMMA. METHODS: Computed tomography (CT) scans (n = 150 nasal cavities) were used to calculate areas of the MAMMA to define surgical limits and extensions. Measurement of distances to critical anatomy landmarks and total area for the MAMMA were calculated. An instructional case illustrating the surgical technique and outcome was also included. RESULTS: Radiological analysis showed a mean distance from the Piriform Aperture (PA) to the anterior limit of the NLD of 1.03 ± 0.18 cm (range 0.59-1.48) and a mean distance from de PA to the posterior limit of the NLD of 1.57 ± 0.22 cm (range 1.02-2.11). The mean distance from the nasal floor to the Hasner's valve was 1.61 ± 0.27 cm (range 1.06-2.52) and the distance from the nasal floor to the insertion of the IT was 2.20 ± 0.36 cm (range 1.70-3.69). Finally, the mean total area for the MAMMA was 4.04 ± 0.52 cm2 (range 3.17-5.53). No complications or recurrence of the pathology were observed in operated patients. CONCLUSION: The MAMMA provides a wide surgical field of the MS walls comparable to more aggressive techniques, with preservation of the sinonasal and lacrimal function. MAMMA is an effective alternative to treat different MS pathologies including benign recurrent maxillary sinus tumors.
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Neoplasias do Seio Maxilar , Ducto Nasolacrimal , Papiloma Invertido , Humanos , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/cirurgia , Seio Maxilar/anatomia & histologia , Endoscopia/métodos , Conchas Nasais/diagnóstico por imagem , Conchas Nasais/cirurgia , Conchas Nasais/patologia , Cavidade Nasal/patologia , Ducto Nasolacrimal/diagnóstico por imagem , Ducto Nasolacrimal/cirurgia , Papiloma Invertido/patologia , Neoplasias do Seio Maxilar/cirurgiaRESUMO
The thermoelectric properties of molecular junctions consisting of a metal Pt electrode contacting [60]fullerene derivatives covalently bound to a graphene electrode have been studied by using a conducting-probe atomic force microscope (c-AFM). The [60]fullerene derivatives are covalently linked to the graphene via two meta-connected phenyl rings, two para-connected phenyl rings, or a single phenyl ring. We find that the magnitude of the Seebeck coefficient is up to nine times larger than that of Au-C60-Pt molecular junctions. Moreover, the sign of the thermopower can be either positive or negative depending on the details of the binding geometry and on the local value of the Fermi energy. Our results demonstrate the potential of using graphene electrodes for controlling and enhancing the thermoelectric properties of molecular junctions and confirm the outstanding performance of [60]fullerene derivatives.
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Microorganisms drive the degradation of organic matter thanks to their enzymatic versatility. However, the structure of lignocellulose poses a great challenge for the microbiota inhabiting a compost pile. Our purpose was to increase the biodegradability of vegetable waste in the early stages of the composting process by applying a microbial consortium with lignocelllulolytic capacity. For this, a previous screening was performed among the culturable microbiota from different composting processes to find inoculants with ligninocellulolytic activity. Selected strains were applied as a pure culture and as a microbial consortium. The starting material was composed of tomato plant and pruning remains mixed in a ratio (50:50 v/v), whose humidity was adjusted to around 65%. To determine the ability of both treatments to activate the biodegradation of the mixtures, moisture, organic matter, ash, C/N ratio, 4-day cumulative respirometric index (AT4) and degradation rates of cellulose, hemicellulose and lignin were evaluated. Subsequently, a real composting process was developed in which the performance of the microbial consortium was compared with the composting process without inoculum (control). According to our tests, three microbial strains (Bacillus safensis, Bacillus licheniformis and Fusarium oxysporum) were selected. The results showed that the application of the bacteria strains at low doses (104 CFU g-1 on the complete residual material of the pile) resulted in higher rates of lignocelullose degradation after 10 days of treatment compared to that observed after application of the fungus in pure culture or untreated controls. The implementation of the strategy described in this work resulted in obtaining compost with better agronomic quality than the uninoculated controls. Therefore, the application of this consortium could be considered as an interesting tool for bioactivation of lignocellulosic waste prior to the composting process.
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Compostagem , Lignina , Lignina/metabolismo , Celulose , Bactérias/metabolismo , SoloRESUMO
BACKGROUND: The past 5 years have seen a proliferation of new treatments for atopic dermatitis (AD). We analyzed recent drug survival data for cyclosporine in this setting. Because the Spanish National Healthcare system requires patients with AD to be treated with cyclosporine before they can be prescribed other systemic treatments, drug survival for cyclosporine may be shorter than in other diseases. MATERIAL AND METHOD: Multicenter, observational, prospective cohort study using data from the Spanish Atopic Dermatitis Registry (BIOBADATOP). Data from the Spanish Registry of Systemic Treatments in Psoriasis (BIOBADADERM) were used to create a comparison cohort. RESULTS: We analyzed data for 130 patients with AD treated with cyclosporine (median drug survival, 1 year). Median cyclosporine survival in the psoriasis comparison group (150 patients) was 0.37 years. Drug survival was significantly longer in AD than in psoriasis (P<.001). CONCLUSION: Drug survival of cyclosporine in the BIOBADATOP registry is similar to that described in other series of patients with AD and longer than that observed in the BIOBADADERM psoriasis registry.
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Dermatite Atópica , Psoríase , Humanos , Ciclosporina/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Imunossupressores/uso terapêutico , Estudos Prospectivos , Psoríase/tratamento farmacológico , Sistema de Registros , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed. OBJECTIVES: the aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP. MATERIALS AND METHODS: we studied a total of 10 SPTCL and 10 LEP patients using targeted Next Generation Sequencing and pyrosequencing. Differences in gene expression between molecular subgroups were investigated using NanoString technology. Clinical data were collected, and correlations sought with the molecular data obtained. RESULTS: the mutational profile of SPTCL and LEP is different. We identified fewer pathogenic mutations than previously reported in SPTCL, noting a single HAVCR2-mutated SPTCL case. Interestingly, 40% of our SPTCL cases showed the pathogenic TP53 (p.Pro72Arg) (P72R) variant. Although cases showing HAVCR2 mutations or the TP53 (P72R) variant had more severe symptomatic disease, none developed hemophagocytic syndrome (HPS). Furthermore, TP53 (P72R)-positive cases were characterized by a lower metabolic signaling pathway and higher levels of CD28 expression and Treg signaling genes. In addition, 30% of our cases featured the same mutation (T735C) of the epigenetic modificatory gene DNMT3A. None of the LEP cases showed mutations in any of the studied genes. CONCLUSIONS: the mutational landscape of SPTCL is broader than previously anticipated. We describe, for the first time, the involvement of the TP53 (P72R) pathogenic variant in this subgroup of tumors, consider the possible role of different genetic backgrounds in the development of SPTCL, and conclude that LEP does not follow the same pathogenic pathway as SPTCL.
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Stimulation of the dorsolateral periaqueductal grey matter (dlPAG) in rats evokes an active defensive behaviour together with a cardiorespiratory response characterised by tachypnoea, tachycardia and hypertension. The dlPAG neurons involved in these responses are excitatory, presumably glutamatergic, due to the presence of vesicular glutamate transporter VGLUT2 within their axon terminals. Previously, our group described a functional interaction between dlPAG and the pontine A5 region. Accordingly, in the present work, in order to characterize the role of glutamate within this interaction, experiments were carried out in spontaneously breathing anaesthetized rats (sodium pentobarbitone 60 mg/kg i.p., suplemented with 20 mg/kg i.p.). The cardiorespiratory response evoked by electrical stimulation of the dlPAG (1 ms pulses, 20-50 µA, given at 100 Hz, during 5 s) was analysed before and after the microinjection, within the A5 region, of either kynurenic acid (non-specific glutamate receptor antagonist; 5-10 nmol), DAP-5 (NMDA antagonist; 1 pmol), CNQX (non-NMDA antagonist; 1 pmol) or MCPG (metabotropic antagonist; 0,1 nmol). Kynurenic acid decreased the intensity of both the tachypnoea (p < 0,001) and tachycardia (p < 0,001) induced by dl-PAG stimulation. Blockade of no-NMDA receptors reduced the increase of respiratory frequency, heart rate and pressor response to dl-PAG stimulation (p < 0,01, p < 0,001, p < 0,05 respectively). Blockade of either NMDA or metabotropic receptors reduced the dlPAG-evoked tachycardia and pressor response (p < 0,01; p < 0,05 respectively). These results suggest a neuromodulatory role for A5 region via glutamate neurotransmission of the dlPAG-evoked cardiorespiratory response, confirming the role of the ventrolateral pons in the neuronal circuits involved in respiratory and heart rate control.