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1.
Vaccines (Basel) ; 9(3)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808916

RESUMO

Limited information is available to determine the effectiveness of Mexico's national influenza vaccination guidelines and inform policy updates. We aim to propose reforms to current influenza vaccination policies based on our analysis of cost-effectiveness studies. This cross-sectional epidemiological study used influenza case, death, discharge and hospitalization data from several influenza seasons and applied a one-year decision-analytic model to assess cost-effectiveness. The primary health outcome was influenza cases avoided; secondary health outcomes were influenza-related events associated with case reduction. By increasing vaccination coverage to 75% in the population aged 12-49 years with risk factors (diabetes, high blood pressure, morbid obesity, chronic renal failure, asthma, pregnancy), and expanding universal vaccination coverage to school-aged children (5-11 years) and adults aged 50-59 years, 7142-671,461 influenza cases; 1-15 deaths; 7615-262,812 healthcare visits; 2886-154,143 emergency room admissions and 2891-97,637 hospitalizations could be prevented (ranges correspond to separate age and risk factor groups), with a net annual savings of 3.90 to 111.99 million USD. Such changes to the current vaccination policy could potentially result in significant economic and health benefits. These data could be used to inform the revision of a vaccination policy in Mexico with substantial social value.

2.
Sci Rep ; 11(1): 8276, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859283

RESUMO

An emerging concern is the influences of early life exposure to environmental toxicants on offspring characteristics in later life. Since recent evidence suggests a transgenerational transference of aberrant phenotypes from exposed-parents to non-exposed offspring related to adult-onset diseases including reproductive phenotype. The transgenerational potential of arsenic a well know genotoxic and epigenetic modifier agent has not been assessed in mammals until now. In this experimental study, we evaluated the transgenerational effects of arsenic in a rat model with chronic exposure to arsenic. Rats chronically exposed to arsenic in drinking water (1 mg As2O3/mL) (F0) were mated to produce the arsenic lineage (F1, F2, and F3). The arsenic toxic effects on were evaluated over the four generations by analyzing the DNA methylation percentage, genotoxicity in WBC and physical and reproductive parameters, including sperm quality parameters and histopathological evaluation of the gonads. Chronic exposure to arsenic caused genotoxic damage (F0-F3) different methylation patterns, alterations in physical and reproductive parameters, aberrant morphology in the ovaries (F0 and F1) and testicles (F1-F3), and a decrease in the quality of sperm (F0-F3, except F2). Parental chronic arsenic exposure causes transgenerational genotoxicity and changes in global DNA methylation which might be associated with reproductive defects in rats. Combined with recent studies reveal that disturbances in the early life of an individual can affect the health of later generations.

3.
Sensors (Basel) ; 21(9)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925583

RESUMO

In recent years, electroencephalographic (EEG) signals have been intensively used in the area of emotion recognition, partcularly in distress identification due to its negative impact on physical and mental health. Traditionally, brain activity has been studied from a frequency perspective by computing the power spectral density of the EEG recordings and extracting features from different frequency sub-bands. However, these features are often individually extracted from single EEG channels, such that each brain region is separately evaluated, even when it has been corroborated that mental processes are based on the coordination of different brain areas working simultaneously. To take advantage of the brain's behaviour as a synchronized network, in the present work, 2-D and 3-D spectral images constructed from common 32 channel EEG signals are evaluated for the first time to discern between emotional states of calm and distress using a well-known deep-learning algorithm, such as AlexNet. The obtained results revealed a significant improvement in the classification performance regarding previous works, reaching an accuracy about 84%. Moreover, no significant differences between the results provided by the diverse approaches considered to reconstruct 2-D and 3-D spectral maps from the original location of the EEG channels over the scalp were noticed, thus suggesting that these kinds of images preserve original spatial brain information.


Assuntos
Eletroencefalografia , Redes Neurais de Computação , Algoritmos , Encéfalo , Emoções
4.
Vaccines (Basel) ; 9(3)2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33668199

RESUMO

The Mexican influenza vaccination program does not include a recommendation for people aged 50-59 years without risk factors for influenza complications, and there are limited data regarding the cost-effectiveness of vaccinating this population. To explore the clinical and economic effects of including this population in the vaccination schedule, we performed a cross-sectional epidemiological study using records (2009-2018) from Mexico's Influenza Surveillance System (SISVEFLU), death records (2010-2015) from the National Mortality Epidemiological and Statistical System, and discharge and hospitalization records (2010-2015) from the Automated Hospital Discharge System databases. A 1-year decision-analytic model was used to assess cost-effectiveness through a decision-tree based on data from SISVEFLU. The primary outcome was influenza cases avoided; with associated influenza-related events as secondary outcomes. Including the population aged 50-59 years without risk factors in Mexico's influenza immunization program would have resulted in 199,500 fewer cases; 67,008 fewer outpatient consultations; 33,024 fewer emergency room consultations; 33,091 fewer hospitalizations; 12 fewer deaths. These reductions equate to a substantial public health benefit as well as an economic benefit; yielding net savings of 49.8 million US dollars over a typical influenza season. Expansion of the current Mexican vaccination schedule to include these people would be a cost-saving and dominant strategy.

5.
Clin Res Hepatol Gastroenterol ; 45(4): 101519, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33636655

RESUMO

INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is a risk factor for liver disease. PASD-positive inclusions have been found unexpectedly in approximately 10% of liver explants in patients with no previous diagnosis of AATD, particularly, in patients with non-alcoholic steatohepatitis (NASH), supporting a synergistic mechanism of liver injury between AATD and environmental factors. We aimed to determine the clinical characteristics of mestizo patients in which AATD was diagnosed before or after liver transplantation. METHODS: Liver explants of patients with cryptogenic, alcoholic, and NAFLD/NASH cirrhosis undergoing orthotopic liver transplantation (OLT) were included. Liver histopathology was assessed by two expert pathologists. Hematoxylin and eosin staining, PASD staining, and confirmatory AAT immunohistochemistry were performed. In explants with positive histopathology, genotyping for SERPINA1 was performed. RESULTS: A total of 180 liver transplants were performed during the study period. Of these, 44 patients with cryptogenic cirrhosis, NASH, and alcoholic cirrhosis were included. Of these patients, two liver explants (4.5%) had PASD-positive inclusions stain and confirmatory immunochemistry. During the period evaluated, another two patients with a diagnosis of AATD before the OLT were also included. The four patients had overweight or obesity, three had type 2 diabetes mellitus, and two developed liver steatosis after the OLT. CONCLUSION: AATD was found to be an infrequent finding in patients with cryptogenic, NASH/NAFLD, and alcoholic cirrhosis in our population. However, it is important to consider this entity as it may represent an additional factor in the appearance and progression of liver fibrosis in patients with metabolic syndrome.

6.
Trop Anim Health Prod ; 53(1): 122, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33443652

RESUMO

To establish the diversity, structure, and phylogenetic relationships among Colombian Creole cattle, six native breeds and one introduced breed were genotyped for 20 microsatellite loci. The average number of alleles per breed ranged from 7050 (Romosinuano) to 10,100 (Casanareño), and the expected heterozygosity ranged from 0.691 (San martinero) to 0.785 (Casanareño). The deviation from the Hardy-Weinberg equilibrium (HWE) was statistically significant (p < 0.05) in 59 out of 120 tests carried out in the six breeds for the 20 microsatellite loci analyzed. Colombian Creole bovine breeds have maintained a high level of genetic differentiation within the same populations (93%), and the rest is explained by differences between breeds (7%). The differentiation pattern and the genetic relationships between the Colombian Creole bovine breeds showed high consistency with the evolutionary history of each. Both the Bayesian grouping analysis and the neighbor-joining tree exhibited a reliable grouping pattern, which revealed two main groups: one comprised by the breeds Blanco Orejinegro, Hartón del Valle, Costeño Con Cuernos, Romosinuano, and San Martinero, and the other one by the Creole breed Casanareño and Zebu. These were probably caused by different historical, reproductive, and geographic isolation precedents, as well as by different levels of inbreeding. This study will help understand the genetic characteristics of Colombian Creole cattle and will benefit future conservation programs.

7.
Entropy (Basel) ; 22(7)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33286505

RESUMO

Atrial fibrillation (AF) is the most common heart rhythm disturbance in clinical practice. It often starts with asymptomatic and very short episodes, which are extremely difficult to detect without long-term monitoring of the patient's electrocardiogram (ECG). Although recent portable and wearable devices may become very useful in this context, they often record ECG signals strongly corrupted with noise and artifacts. This impairs automatized ulterior analyses that could only be conducted reliably through a previous stage of automatic identification of high-quality ECG intervals. So far, a variety of techniques for ECG quality assessment have been proposed, but poor performances have been reported on recordings from patients with AF. This work introduces a novel deep learning-based algorithm to robustly identify high-quality ECG segments within the challenging environment of single-lead recordings alternating sinus rhythm, AF episodes and other rhythms. The method is based on the high learning capability of a convolutional neural network, which has been trained with 2-D images obtained when turning ECG signals into wavelet scalograms. For its validation, almost 100,000 ECG segments from three different databases have been analyzed during 500 learning-testing iterations, thus involving more than 320,000 ECGs analyzed in total. The obtained results have revealed a discriminant ability to detect high-quality and discard low-quality ECG excerpts of about 93%, only misclassifying around 5% of clean AF segments as noisy ones. In addition, the method has also been able to deal with raw ECG recordings, without requiring signal preprocessing or feature extraction as previous stages. Consequently, it is particularly suitable for portable and wearable devices embedding, facilitating early detection of AF as well as other automatized diagnostic facilities by reliably providing high-quality ECG excerpts to further processing stages.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33225569

RESUMO

The role of wildlife in the epidemiology of antimicrobial resistance is unclear. Raccoons in North America can carry a variety of enteric bacteria, with associated antimicrobial resistance, that could infect humans and livestock. The potential for raccoons to carry these bacteria in Europe, where they are an invasive species, has not been explored. Our objectives were to determine the prevalence of Escherichia coli with associated antimicrobial resistance in raccoons from the Madrid region of Spain and to determine whether they are carriers of potential human pathogens, including verotoxin-producing E. coli (VTEC) and enteropathogenic E. coli (EPEC). In total, we tested 237 E. coli isolates from the faeces of 83 euthanized raccoons for susceptibility to 14 antimicrobial agents and the presence of VTEC and EPEC. Antimicrobial resistance to at least one antimicrobial was detected in the faeces of 51% (42/83; 95% CI, 40.1-61.1) of the raccoons tested. A high percentage of raccoons carried, in their faeces, E. coli isolates resistant to ampicillin (33%), streptomycin (33%), tetracycline (30%), sulphafurazole (31%) and trimethoprim-sulphamethoxazole (23%). We detected one isolate of extended-spectrum ß-lactamase-producing E. coli from the faeces of one raccoon. We detected VTEC in the faeces of one raccoon, and EPEC in the faeces of 12% (10/83) of the raccoons. Of the raccoons that carried EPEC in their faeces, 60% (6/10) carried EPEC isolates that exhibited characteristics associated with pathogenicity in humans. Raccoons in Madrid can carry pathogenic and antimicrobial-resistant E. coli in their faeces and may be a risk to public health because of their potential to contaminate food and the environment with their faeces.

9.
Vet Immunol Immunopathol ; 230: 110148, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33189999

RESUMO

Human leishmaniosis caused by Leishmania infantum is a zoonotic disease, with dogs as the main reservoir in Mediterranean Basin countries. The largest European outbreak of human leishmaniosis declared in the southwestern Madrid region (Spain) is characterized by unusual epidemiological and clinical features, such as the emergence of new wild reservoirs (hares and rabbits), whereas the seroprevalence, infection, and severity of canine leishmaniosis have not substantially changed since the first studies conducted in Madrid before the outbreak. Previous studies reported that L. infantum isolates from the Madrid leishmaniosis focus displayed elevated virulence in in vivo models of infection and increased infectivity in murine target cells. With the aim of studying whether changes in the host-parasite interaction and virulence profile have developed, we first assessed the behaviour of one circulating isolate of the outbreak, IPER/ES/2012/BOS1FL1 (BOS1FL1), compared to that of a well-characterized strain from canine leishmaniosis, MCAN/ES/1996/BCN150 (BCN150), in terms of infection capacity (percentage of infected cells, representing infectivity, and number of amastigotes per infected cell, representing the intensity of infection) in canine monocytes and macrophages. BCN150 displayed significantly higher infectivity (76.82 ±â€¯4.40 vs 38.58 ±â€¯2.19; P <  0.0001) and intensity of infection (3.64 ± 0.13 vs 1.83 ±â€¯0.12; P <  0.0001) than BOS1FL1 when interacting with canine cells. Our ROS induction results did not differ significantly between the two isolates or with the responses previously described for other L. infantum isolates. Paradoxically, increased resilience to hydrogen peroxide exposure was observed for BOS1FL1 (% viability 40.62 ±â€¯5.54 vs 26.37 ±â€¯2.93; P = 0.039). Finally, we demonstrated that a decreased intracellular load of BOS1FL1 was associated with increased IFN-γ (261.21 ±â€¯26.29 vs 69.80 ±â€¯9.02; P = 0.0151) and decreased IL-10 production (165.06 ±â€¯23.87 vs 264.41 ±â€¯30.58; P = 0.0002). In this study, we provide the first detailed insight into the differences between the isolate BOS1FL1 from the outbreak in Madrid and the well-characterized strain BCN150 MON-1 obtained from a dog in their response to interacting with canine cells. However, further studies are necessary to shed light on the immune mechanisms resulting in BOS1FL1 exhibiting less virulent behaviour in canine cells than in cells derived from other host species.

10.
Pharmacol Rep ; 72(6): 1529-1537, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33165762

RESUMO

BACKGROUND: This study was aimed to assess the efficacy and safety of tocilizumab (TCZ) and to investigate the factors related to the progress and mortality of patients with a secondary cytokine release syndrome caused by SARS-CoV-2. METHODS: A retrospective descriptive observational study of hospitalised patients with a positive polymerase chain reaction (PCR) result for SARS-CoV-2 and whose clinical evolution required the administration of one or more doses of TCZ was conducted. Demographic variables, clinical evolution, radiologic progress and analytical parameters were analysed on days 1, 3 and 5 after administration the first dose of TCZ. RESULTS: A total of 75 patients with a clinical history of Accurate Respiratory Distress Syndrome (ARDS) were analysed, among whom, 19 had mild ARDS (25.3%), 37 moderate ARDS (49.4%) and 19 severe ARDS (25.3%). Lymphocytopenia and high levels of PCR, D-Dimer and IL-6 were observed in almost all the patients (91.8%). Treatment with TCZ was associated with a reduction of lymphocytopenia, C-reactive protein (CRP) levels, severe ARDS cases and fever. Although a better evolution of PaO2/FiO2 was observed in patients who received two or more doses of TCZ (38/75), there was an increase in their mortality (47.4%) and ICU admission (86.8%). The 30-day mortality rate was 30.7% (20.5-42.4% CI) being hypertension, high initial D-dimer levels and ICU admission the only predictive factors found. CONCLUSION: Based on our results, treatment with TCZ was associated with a fever, swelling and ventilator support improvement. However, there is no evidence that the administration of two or more doses of TCZ was related to a mortality decrease.

11.
Sci Rep ; 10(1): 14548, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883988

RESUMO

Emotional response in aging is typically studied using the dimensional or the discrete models of emotion. Moreover, it is typically studied using subjective or physiological variables but not using both perspectives simultaneously. Additionally, tenderness is neglected in emotion induction procedures with older adults, with the present work being the first to include the study of physiological tenderness using film clips. This study integrated two separate approaches to emotion research, comparing 68 younger and 39 older adults and using a popular set of film clips to induce tenderness, amusement, anger, fear, sadness and disgust emotions. The direction of subjective emotional patterns was evaluated with self-reports and that of physiological emotional patterns was evaluated with a wearable emotion detection system. The findings suggest a dual-process framework between subjective and physiological responses, manifested differently in young and older adults. In terms of arousal, the older adults exhibited higher levels of subjective arousal in negative emotions and tenderness while young adults showed higher levels of physiological arousal in these emotions. These findings yield information on the multidirectionality of positive and negative emotions, corroborating that emotional changes in the adult lifespan appear to be subject to the relevance of the emotion elicitor to each age group.

12.
Chembiochem ; 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32815664

RESUMO

Epigenetic marks are modest chemical modifications on DNA and histone proteins that regulate the activation or silencing of genes through modulation of the intermolecular interactions between the DNA strands and the protein machinery. The process is complex and not always well understood. One of the systems studied in greater detail is the epigenetic mark on H3K9: lysine 9 of histone 3. The degree of methylation or acetylation of this histone is linked to silencing or activation of the corresponding gene, but it is not clear which effect each mark has in gene expression. We shed light on this particular methylation process by using density functional theory (DFT) calculations. First, we built a model consisting of a DNA double strand containing three base pairs and a sequence of three amino acids of the histone's tail. Then, we computed the modulation introduced into the intermolecular interactions by each epigenetic modification: from mono- to trimethylation and acetylation. The calculations show that whereas acetylation and trimethylation result in a reduction of the DNA-peptide interaction; non-, mono-, and dimethylation increase the intermolecular interactions. Such observations compare well with the findings reported in the literature, and highlight the correlation between the balance of intermolecular forces and biological properties, simultaneously advancing quantum-mechanical studies of large biochemical systems at molecular level through the use of DFT methods.

13.
Vaccines (Basel) ; 8(3)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32630347

RESUMO

Visceral leishmaniosis (VL) caused by Leishmania infantum is a disease with an increasing prevalence worldwide. Treatments are expensive, toxic, and ineffective. Therefore, vaccination seems to be a promising approach to control VL. Peptide-based vaccination is a useful method due to its stability, absence of local side effects, and ease of scaling up. In this context, bioinformatics seems to facilitate the use of peptides, as this analysis can predict high binding affinity epitopes to MHC class I and II molecules of different species. We have recently reported the use of HisAK70 DNA immunization in mice to induce a resistant phenotype against L. major, L. infantum, and L. amazonensis infections. In the present study, we used bioinformatics tools to select promising multiepitope peptides (HisDTC and AK) from the polyprotein encoded in the HisAK70 DNA to evaluate their immunogenicity in the murine model of VL by L. infantum. Our results revealed that both multiepitope peptides were able to induce the control of VL in mice. Furthermore, HisDTC was able to induce a better cell-mediated immune response in terms of reduced parasite burden, protective cytokine profile, leishmanicidal enzyme modulation, and specific IgG2a isotype production in immunized mice, before and after infectious challenge. Overall, this study indicates that the HisDTC chimera may be considered a satisfactory tool to control VL because it is able to activate a potent CD4+ and CD8+ T-cell protective immune responses.

14.
Transbound Emerg Dis ; 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32668083

RESUMO

Recent anthropic activity related to the construction of the Bosquesur Green Park in a large urban setting in Madrid (Spain) has resulted in the largest reported community outbreak of human leishmaniosis in Europe. Previous phylogenetic and molecular-typing studies of parasite isolates have implicated the Leishmania infantum ITS-Lombardi genotype in this outbreak. In an unusual scenario, visceral leishmaniosis (VL) is affecting a significant number of individuals, suggesting that an increase in parasite virulence has occurred. In this work, using an in vivo BALB/c model of VL, we aimed to investigate the properties of emergent virulence of the L. infantum POL2FL7 and BOS1FL1 isolates obtained from Phlebotomus perniciosus collected in the outbreak area and compare them with those of the well-characterized strain BCN150 MON-1 isolated from a dog. The P. perniciosus specimens were collected during an entomological survey conducted in the transmission season of 2012. We observed a range of virulence phenotypes from moderately to highly aggressive after 5 weeks of infection. IV challenge of mice with outbreak isolates from sand flies induced higher splenic and liver parasite burdens, higher serological titres of specific anti-Leishmania antibodies and impaired capacities to control infection, as revealed by the arginine metabolism and low ratios of Th1/Th2 cytokine profiles analysed, compared with the corresponding measures evaluated in mice infected with the BCN150 strain. The BOS1FL1 isolate showed the highest degree of virulence among the isolates, superior to that of POL2FL7, as evidenced by the analysed biomarkers and the histopathological severity of liver lesions. These results provide insight into how L. infantum isolates from sand flies collected in the outbreak area have been able to affect not only immunosuppressed patients but also middle-aged people with normal immunocompetence in the largest human VL outbreak in Europe.

15.
Int J Neural Syst ; 30(7): 2050031, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32507059

RESUMO

Early detection of stress condition is beneficial to prevent long-term mental illness like depression and anxiety. This paper introduces an accurate identification of stress/calm condition from electrodermal activity (EDA) signals. The acquisition of EDA signals from a commercial wearable as well as their storage and processing are presented. Several time-domain, frequency-domain and morphological features are extracted over the skin conductance response of the EDA signals. Afterwards, a classification is undergone by using several classical support vector machines (SVMs) and deep support vector machines (D-SVMs). In addition, several binary classifiers are also compared with SVMs in the stress/calm identification task. Moreover, a series of video clips evoking calm and stress conditions have been viewed by 147 volunteers in order to validate the classification results. The highest F1-score obtained for SVMs and D-SVMs are 83% and 92%, respectively. These results demonstrate that not only classical SVMs are appropriate for classification of biomarker signals, but D-SVMs are very competitive in comparison to other classification techniques. In addition, the results have enabled drawing useful considerations for the future use of SVMs and D-SVMs in the specific case of stress/calm identification.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32432089

RESUMO

Although biological upgrading of lignocellulosic sugars represents a promising and sustainable route to bioplastics, diverse and variable feedstock compositions (e.g., glucose from the cellulose fraction and xylose from the hemicellulose fraction) present several complex challenges. Specifically, sugar mixtures are often incompletely metabolized due to carbon catabolite repression while composition variability further complicates the optimization of co-utilization rates. Benefiting from several unique features including division of labor, increased metabolic diversity, and modularity, synthetic microbial communities represent a promising platform with the potential to address persistent bioconversion challenges. In this work, two unique and catabolically orthogonal Escherichia coli co-cultures systems were developed and used to enhance the production of D-lactate and succinate (two bioplastic monomers) from glucose-xylose mixtures (100 g L-1 total sugars, 2:1 by mass). In both cases, glucose specialist strains were engineered by deleting xylR (encoding the xylose-specific transcriptional activator, XylR) to disable xylose catabolism, whereas xylose specialist strains were engineered by deleting several key components involved with glucose transport and phosphorylation systems (i.e., ptsI, ptsG, galP, glk) while also increasing xylose utilization by introducing specific xylR mutations. Optimization of initial population ratios between complementary sugar specialists proved a key design variable for each pair of strains. In both cases, ∼91% utilization of total sugars was achieved in mineral salt media by simple batch fermentation. High product titer (88 g L-1 D-lactate, 84 g L-1 succinate) and maximum productivity (2.5 g L-1 h-1 D-lactate, 1.3 g L-1 h-1 succinate) and product yield (0.97 g g-total sugar-1 for D-lactate, 0.95 g g-total sugar-1 for succinate) were also achieved.

17.
Nat Mater ; 19(10): 1114-1123, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32451513

RESUMO

Cells comprise mechanically active matter that governs their functionality, but intracellular mechanics are difficult to study directly and are poorly understood. However, injected nanodevices open up opportunities to analyse intracellular mechanobiology. Here, we identify a programme of forces and changes to the cytoplasmic mechanical properties required for mouse embryo development from fertilization to the first cell division. Injected, fully internalized nanodevices responded to sperm decondensation and recondensation, and subsequent device behaviour suggested a model for pronuclear convergence based on a gradient of effective cytoplasmic stiffness. The nanodevices reported reduced cytoplasmic mechanical activity during chromosome alignment and indicated that cytoplasmic stiffening occurred during embryo elongation, followed by rapid cytoplasmic softening during cytokinesis (cell division). Forces greater than those inside muscle cells were detected within embryos. These results suggest that intracellular forces are part of a concerted programme that is necessary for development at the origin of a new embryonic life.

18.
Adv Appl Microbiol ; 111: 33-87, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32446412

RESUMO

The rapid development in the field of metabolic engineering has enabled complex modifications of metabolic pathways to generate a diverse product portfolio. Manipulating substrate uptake and product export is an important research area in metabolic engineering. Optimization of transport systems has the potential to enhance microbial production of renewable fuels and chemicals. This chapter comprehensively reviews the transport systems critical for microbial production as well as current genetic engineering strategies to improve transport functions and thus production metrics. In addition, this chapter highlights recent advancements in engineering microbial efflux systems to enhance cellular tolerance to industrially relevant chemical stress. Lastly, future directions to address current technological gaps are discussed.

19.
Nanomaterials (Basel) ; 10(5)2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32392901

RESUMO

Micrometer-sized silicon chips have been demonstrated to be cell-internalizable, offering the possibility of introducing in cells even smaller nanoelements for intracellular applications. On the other hand, silicon nanowires on extracellular devices have been widely studied as biosensors or drug delivery systems. Here, we propose the integration of silicon nanowires on cell-internalizable chips in order to combine the functional features of both approaches for advanced intracellular applications. As an initial fundamental study, the cellular uptake in HeLa cells of silicon 3 µm × 3 µm nanowire-based chips with two different morphologies was investigated, and the results were compared with those of non-nanostructured silicon chips. Chip internalization without affecting cell viability was achieved in all cases; however, important cell behavior differences were observed. In particular, the first stage of cell internalization was favored by silicon nanowire interfaces with respect to bulk silicon. In addition, chips were found inside membrane vesicles, and some nanowires seemed to penetrate the cytosol, which opens the door to the development of silicon nanowire chips as future intracellular sensors and drug delivery systems.

20.
Oral Oncol ; 105: 104635, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32247986

RESUMO

INTRODUCTION: Incomplete head and neck cancer resection occurs in up to 85% of cases, leading to increased odds of local recurrence and regional metastases; thus, image-guided surgical tools for accurate, in situ and fast detection of positive margins during head and neck cancer resection surgery are urgently needed. Oral epithelial dysplasia and cancer development is accompanied by morphological, biochemical, and metabolic tissue and cellular alterations that can modulate the autofluorescence properties of the oral epithelial tissue. OBJECTIVE: This study aimed to test the hypothesis that autofluorescence biomarkers of oral precancer and cancer can be clinically imaged and quantified by means of multispectral fluorescence lifetime imaging (FLIM) endoscopy. METHODS: Multispectral autofluorescence lifetime images of precancerous and cancerous lesions from 39 patients were imaged in vivo using a novel multispectral FLIM endoscope and processed to generate widefield maps of biochemical and metabolic autofluorescence biomarkers of oral precancer and cancer. RESULTS: Statistical analyses applied to the quantified multispectral FLIM endoscopy based autofluorescence biomarkers indicated their potential to provide contrast between precancerous/cancerous vs. healthy oral epithelial tissue. CONCLUSION: To the best of our knowledge, this study represents the first demonstration of label-free biochemical and metabolic clinical imaging of precancerous and cancerous oral lesions by means of widefield multispectral autofluorescence lifetime endoscopy. Future studies will focus on demonstrating the capabilities of endogenous multispectral FLIM endoscopy as an image-guided surgical tool for positive margin detection during head and neck cancer resection surgery.

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