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1.
Nucleic Acids Res ; 51(22): 12522-12536, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37941137

RESUMO

The widespread Pseudomonas genus comprises a collection of related species with remarkable abilities to degrade plastics and polluted wastes and to produce a broad set of valuable compounds, ranging from bulk chemicals to pharmaceuticals. Pseudomonas possess characteristics of tolerance and stress resistance making them valuable hosts for industrial and environmental biotechnology. However, efficient and high-throughput genetic engineering tools have limited metabolic engineering efforts and applications. To improve their genome editing capabilities, we first employed a computational biology workflow to generate a genus-specific library of potential single-stranded DNA-annealing proteins (SSAPs). Assessment of the library was performed in different Pseudomonas using a high-throughput pooled recombinase screen followed by Oxford Nanopore NGS analysis. Among different active variants with variable levels of allelic replacement frequency (ARF), efficient SSAPs were found and characterized for mediating recombineering in the four tested species. New variants yielded higher ARFs than existing ones in Pseudomonas putida and Pseudomonas aeruginosa, and expanded the field of recombineering in Pseudomonas taiwanensisand Pseudomonas fluorescens. These findings will enhance the mutagenesis capabilities of these members of the Pseudomonas genus, increasing the possibilities for biotransformation and enhancing their potential for synthetic biology applications. .


Assuntos
Edição de Genes , Pseudomonas , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/metabolismo , Edição de Genes/métodos , Engenharia Metabólica , Pseudomonas/genética , Pseudomonas putida/genética
2.
J Urol ; 211(2): 294-304, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37930962

RESUMO

PURPOSE: Transcutaneous spinal cord stimulation (TSCS) is a novel neuromodulation modality developed to promote functional restoration in patients with neurological injury or disease. Previous pilot data suggest that lower urinary tract dysfunction (LUTD) due to stroke may be partially alleviated by TSCS. In this study, we examine the mechanism of this effect by evaluating bladder-related brain activity in patients before and after TSCS therapy and comparing it to healthy volunteers. MATERIALS AND METHODS: Patients who developed storage LUTD after a stroke and healthy volunteers without LUTD were recruited. Patients and healthy volunteers underwent simultaneous urodynamics and functional MRI. Patients then completed 24 biweekly sessions of TSCS and underwent another simultaneous urodynamics-functional MRI study. Clinical outcomes were assessed using validated questionnaires and voiding diary. RESULTS: Fifteen patients and 16 healthy volunteers completed the study. Following TSCS, patients exhibited increased blood-oxygen-level-dependent activity in areas including periaqueductal grey, the insula, the lateral prefrontal cortex, and motor cortex. Prior to TSCS therapy, healthy controls exhibited higher blood-oxygen-level-dependent activity in 17 regions, including multiple regions in the prefrontal cortex and basal ganglia. These differences were attenuated after TSCS with no frontal brain differences remaining between healthy volunteers and stroke participants who completed therapy. Neuroimaging changes were complemented by clinically significant improvements in questionnaire scores and voiding diary parameters. CONCLUSIONS: TSCS therapy modulated bladder-related brain activity, reducing differences between healthy volunteers and stroke patients with LUTD. These changes, alongside improved clinical outcomes, suggest TSCS as a promising approach for LUTD management.


Assuntos
Sintomas do Trato Urinário Inferior , Estimulação da Medula Espinal , Acidente Vascular Cerebral , Humanos , Micção/fisiologia , Projetos Piloto , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/terapia , Sintomas do Trato Urinário Inferior/diagnóstico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Encéfalo/diagnóstico por imagem , Oxigênio
3.
Mol Pharm ; 21(3): 1436-1449, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38291705

RESUMO

Small interfering RNAs (siRNAs) have emerged as a powerful tool to manipulate gene expression in vitro. However, their potential therapeutic application encounters significant challenges, such as degradation in vivo, limited cellular uptake, and restricted biodistribution, among others. This study evaluates the siRNA delivery efficiency of three different lipid-substituted polyethylenimine (PEI)-based carriers, named Leu-Fect A-C, to different organs in vivo, including xenograft tumors, when injected into the bloodstream of mice. The siRNA analysis was undertaken by stem-loop RT-PCR, followed by qPCR or digital droplet PCR. Formulating siRNAs with a Leu-Fect series of carriers generated nanoparticles that effectively delivered the siRNAs into K652 and MV4-11 cells, both models of leukemia. The Leu-Fect carriers were able to successfully deliver BCR-Abl and FLT3 siRNAs into leukemia xenograft tumors in mice. All three carriers demonstrated significantly enhanced siRNA delivery into organs other than the liver, including the xenograft tumors. Preferential biodistribution of siRNAs was observed in the lungs and spleen. Among the delivery systems, Leu-Fect A exhibited the highest biodistribution into organs. In conclusion, lipid-substituted PEI-based delivery systems offer improvements in addressing pharmacokinetic challenges associated with siRNA-based therapies, thus opening avenues for their potential translation into clinical practice.


Assuntos
Leucemia , Neoplasias , Humanos , Camundongos , Animais , RNA Interferente Pequeno/genética , Polietilenoimina , Distribuição Tecidual , Leucemia/genética , Leucemia/terapia , Lipídeos
4.
Sensors (Basel) ; 24(12)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38931674

RESUMO

The transition to a low-carbon economy is one of the main challenges of our time. In this context, solar energy, along with many other technologies, has been developed to optimize performance. For example, solar trackers follow the sun's path to increase the generation capacity of photovoltaic plants. However, several factors need consideration to further optimize this process. Important variables include the distance between panels, surface reflectivity, bifacial panels, and climate variations throughout the day. Thus, this paper proposes an artificial intelligence-based algorithm for solar trackers that takes all these factors into account-mainly weather variations and the distance between solar panels. The methodology can be replicated anywhere in the world, and its effectiveness has been validated in a real solar plant with bifacial panels located in northeastern Brazil. The algorithm achieved gains of up to 7.83% on a cloudy day and obtained an average energy gain of approximately 1.2% when compared to a commercial solar tracker algorithm.

5.
Photochem Photobiol Sci ; 22(10): 2373-2387, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37486529

RESUMO

Hydrogen peroxide (H2O2) is an important molecule that regulates antioxidant responses that are crucial for plant stress resistance. Exposure to low levels of ultraviolet-B radiation (UV-B, 280-315 nm) can also activate antioxidant defenses and acclimation responses. However, how H2O2 and UV-B interact to promote stress acclimation remains poorly understood. In this work, a transgenic model of Nicotiana tabacum cv Xanthi nc, with elevated Mn-superoxide dismutase (Mn-SOD) activity, was used to study the interaction between the constitutive overproduction of H2O2 and a 14-day UV-B treatment (1.75 kJ m-2 d-1 biologically effective UV-B). Subsequently, these plants were subjected to a 7-day moderate drought treatment to evaluate the impact on drought resistance of H2O2- and UV-dependent stimulation of the plants' antioxidant system. The UV-B treatment enhanced H2O2 levels and altered the antioxidant status by increasing the epidermal flavonol index, Trolox Equivalent Antioxidant Capacity, and catalase, peroxidase and phenylalanine ammonia lyase activities in the leaves. UV-B also retarded growth and suppressed acclimation responses in highly H2O2-overproducing transgenic plants. Plants not exposed to UV-B had a higher drought resistance in the form of higher relative water content of leaves. Our data associate the interaction between Mn-SOD transgene overexpression and the UV-B treatment with a stress response. Finally, we propose a hormetic biphasic drought resistance response curve as a function of leaf H2O2 content in N. tabacum cv Xanthi.


Assuntos
Antioxidantes , Peróxido de Hidrogênio , Nicotiana/genética , Secas , Superóxido Dismutase/genética , Folhas de Planta/fisiologia , Aclimatação
6.
Neurourol Urodyn ; 42(6): 1362-1373, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37166006

RESUMO

INTRODUCTION: Neurogenic bowel dysfunction is commonly encountered after a spinal cord injury (SCI), leading to a tremendous impact on quality of life (QOL). The neurogenic bowel dysfunction score (NBDS) is commonly used to measure the severity of bowel dysfunction and predict QOL. However, there is no comprehensive instrument to assess bowel-specific QOL for SCI patients. Instead, the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) questionnaire evaluates the impact of bowel dysfunction on several aspects of QOL, although this questionnaire has not been validated for the SCI population. Motivated by the compelling need of instruments to accurately evaluate the QOL in patients who develope NBD after SCI, we aimed to assess the construct, content, and face validity of IBS-QOL in this population. METHODS: Adult SCI patients with at least 3 months after their injury were recruited from the outpatient clinic of a national rehabilitation hospital. Patients completed the NBDS and IBS-QOL via telephone interview or paper survey in the clinic. Content and face validity were assessed via interviews with professionals with expertise in providing chronic care for SCI, as well as a subgroup of patients. Construct validity was assessed using the hypotheses testing method. Internal consistency was assessed using Cronbach's ⍺. Factor analysis was performed to assess the dimensionality of the IBS-QOL in the SCI population. RESULTS: A total of 106 patients with a median age of 45.5 years (interquartile range: 21-79) participated in the study. The majority of the sample were men (n = 82, 77%) and had endured thoracolumbar injuries (n = 74, 71.2%). Twelve patients (seven English- and five Spanish speakers) and six professionals took part in content/face validation interviews. The median IBS-QOL total score was 15.91/100 (interquartile range: 4.55-33.14). IBS-QOL differentiated the subgroups of patients with severe bowel symptoms in terms of uneasiness, sweating, or headaches during bowel emptying (p = 0.0003), time spent on bowel emptying (p = 0.0065), flatus incontinence (p = 0.0076), and overall satisfaction with bowel function (p < 0.001), demonstrating its adequate construct validity. Interviews with the patients and professionals supported the comprehensiveness, comprehensibility, and relevance of IBS-QOL for assessment of bowel-related QOL in the SCI population. Item-level analysis of professional responses showed that 97% of questions were relevant to the construct and population of interest. Internal consistency analysis yielded a Cronbach's ⍺ of 0.9684. Exploratory factor analysis yielded six underlying factors which cumulatively accounted for 72.21% of the total variance, reflecting the dimensionality of bowel-related QOL in SCI population. DISCUSSION: IBS-QOL questionnaire is a comprehensive measure of bowel-related QOL which encompasses the concerns of SCI patients. Our findings support the content, face and construct validity of IBS-QOL as a measure of bowel-related QOL in SCI. Further studies are warranted to assess the reliability and responsiveness of IBS-QOL, and to evaluate its performance across different patient populations.


Assuntos
Síndrome do Intestino Irritável , Intestino Neurogênico , Traumatismos da Medula Espinal , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Qualidade de Vida , Intestino Neurogênico/etiologia , Intestino Neurogênico/diagnóstico , Reprodutibilidade dos Testes , Psicometria , Traumatismos da Medula Espinal/complicações , Inquéritos e Questionários
7.
Mol Biol Rep ; 50(6): 4851-4863, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37039999

RESUMO

BACKGROUND: The Central American (Mazama temama) and the Yucatán Peninsula brocket deer (Odocoileus pandora) are deer species with cryptic habits, and little is known about their biology. Odocoileus pandora is listed as Vulnerable on the 2015 IUCN Red List of Threatened Species, while M. temama is considered Data Deficient; however, it currently faces a decreasing population trend. METHODS AND RESULTS: We assembled the complete mitochondrial genome for two M. temama specimens and one complete and one partial for O. pandora from Illumina 150 bp paired-end reads. The mitogenomes of M. temama and O. pandora have a length of 16,479-16,480 and 16,419 bp, respectively, AT-biased; they consist of 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one non-coding control region, most of them follow a transcription direction in the heavy strand of the molecule. The mitochondrial genome of O. pandora shows some particularities compared to other deer species, like a shorter control region of 987-990 bp and a cytochrome b gene with a length of 1,143 bp. Our phylogenetic analyses confirm the close affinity of M. temama to South American M. americana and the nested position of the genus Odocoileus, including O. pandora, into the genus Mazama. CONCLUSIONS: Here, we described for the first time the complete mitochondrial genome for these two species. While our study provides additional information about the taxonomic status of the northern neotropical brocket deer, further research is needed to solve the complicated taxonomy of neotropical deer.


Assuntos
Cervos , Genoma Mitocondrial , Animais , Filogenia , Genoma Mitocondrial/genética , México , Cervos/genética , América Central
8.
Colorectal Dis ; 25(10): 2033-2042, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37712246

RESUMO

AIM: This study aimed to assess technical aspects and clinical results of a new minimally invasive technique in parastomal hernia (PSH) repair, full endoscopic retromuscular access, after 2 years of follow-up. METHODS: Data from consecutive patients requiring minimally invasive ventral PSH repair were collected from 2019 to 2022. The inclusion criteria were patients aged between 18 and 80 years old with symptomatic PSH. Demographics and perioperative and postoperative data were collected. Postoperative pain and functional recovery were compared with preoperative data. RESULTS: Twelve patients with symptomatic PSH were included. The mean PSH defect area was 16.2 cm2 and the mean midline defect was 8.7 cm2 . No intra-operative complications or conversion to open surgery were detected. One patient (8%) required postoperative readmission due to partial bowel obstruction symptoms that required catheterization of the stoma. Pain significantly worsened after the first postoperative day compared to preoperative data but improved after the first postoperative month compared to the first postoperative week and after the 90th postoperative day compared to the first postoperative month, with significant differences. Significant restriction improvement was identified when 30 days after surgery data were compared to preoperative data and when the 180th postoperative day results were compared to 30 days after surgery. The average follow-up was 29 months. During the follow-up no clinical or radiological recurrence was observed. CONCLUSION: This paper shows low rate of intra- and postoperative complications with significant improvement in terms of pain activities restriction compared to preoperatory. After 29 months follow-up, no recurrence was identified, confirming that this approach offers good mid-term results.


Assuntos
Hérnia Ventral , Hérnia Incisional , Laparoscopia , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Colostomia/efeitos adversos , Colostomia/métodos , Seguimentos , Hérnia Ventral/cirurgia , Estudos Prospectivos , Herniorrafia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Laparoscopia/métodos , Dor Pós-Operatória , Telas Cirúrgicas/efeitos adversos , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia
9.
Adv Exp Med Biol ; 1396: 19-33, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36454457

RESUMO

Metabolic and cardiovascular diseases are world-concerning pathologies that affect an important percentage of the population. Nowadays, advances in the genetic background of these diseases allow new approaches to models and therapies, as well as different gene edition trials. Furthermore, technological improvements in gene editing go along with the development of new online and biocomputational tools that provide us alternative ways to explore pathologies. In this chapter, historical gene editing methods are discussed but focusing on CRISPR-Cas system in detail and also online resources available to perform these types of experiments. Here, the different strategies for gene editing and their online tools are gathered, putting the light on its application in the study and treatment of cardiovascular and metabolic diseases.


Assuntos
Sistema Cardiovascular , Doenças Metabólicas , Humanos , Edição de Genes , Doenças Metabólicas/genética , Doenças Metabólicas/terapia , Sistemas CRISPR-Cas/genética , Bases de Dados Factuais
10.
Int J Mol Sci ; 24(4)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36835435

RESUMO

The function of chaperones is to correct or degrade misfolded proteins inside the cell. Classic molecular chaperones such as GroEL and DnaK have not been found in the periplasm of Yersinia pseudotuberculosis. Some periplasmic substrate-binding proteins could be bifunctional, such as OppA. Using bioinformatic tools, we try to elucidate the nature of the interactions between OppA and ligands from four proteins with different oligomeric states. Using the crystal structure of the proteins Mal12 alpha-glucosidase from Saccharomyces cerevisiae S288C, LDH rabbit muscle lactate dehydrogenase, EcoRI endonuclease from Escherichia coli and THG Geotrichum candidum lipase, a hundred models were obtained in total, including five different ligands from each enzyme with five conformations of each ligand. The best values for Mal12 stem from ligands 4 and 5, with conformation 5 for both; for LDH, ligands 1 and 4, with conformations 2 and 4, respectively; for EcoRI, ligands 3 and 5, with conformation 1 for both; and for THG, ligands 2 and 3, with conformation 1 for both. The interactions were analyzed with LigProt, and the length of the hydrogen bridges has an average of 2.8 to 3.0 Å. The interaction within the OppA pocket is energetically favored due to the formation of hydrogen bonds both of OppA and of the selected enzymes. The Asp 419 residue is important in these junctions.


Assuntos
Proteínas de Bactérias , Chaperonas Moleculares , Proteínas Periplásmicas de Ligação , Yersinia pseudotuberculosis , Animais , Coelhos , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Proteínas de Transporte/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Ligantes , Chaperonas Moleculares/metabolismo , Proteínas Periplásmicas de Ligação/metabolismo , Ligação Proteica , Yersinia pseudotuberculosis/metabolismo
11.
Hum Mol Genet ; 29(3): 418-431, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31875875

RESUMO

Brain cholesterol homeostasis is altered in Huntington's disease (HD), a neurodegenerative disorder caused by the expansion of a CAG nucleotide repeat in the HTT gene. Genes involved in the synthesis of cholesterol and fatty acids were shown to be downregulated shortly after the expression of mutant huntingtin (mHTT) in inducible HD cells. Nuclear levels of the transcription factors that regulate lipid biogenesis, the sterol regulatory element-binding proteins (SREBP1 and SREBP2), were found to be decreased in HD models compared to wild-type, but the underlying causes were not known. SREBPs are synthesized as inactive endoplasmic reticulum-localized precursors. Their mature forms (mSREBPs) are generated upon transport of the SREBP precursors to the Golgi and proteolytic cleavage, and are rapidly imported into the nucleus by binding to importin ß. We show that, although SREBP2 processing into mSREBP2 is not affected in YAC128 HD mice, mSREBP2 is mislocalized to the cytoplasm. Chimeric mSREBP2-and mSREBP1-EGFP proteins are also mislocalized to the cytoplasm in immortalized striatal cells expressing mHTT, in YAC128 neurons and in fibroblasts from HD patients. We further show that mHTT binds to the SREBP2/importin ß complex required for nuclear import and sequesters it in the cytoplasm. As a result, HD cells fail to upregulate cholesterogenic genes under sterol-depleted conditions. These findings provide mechanistic insight into the downregulation of genes involved in the synthesis of cholesterol and fatty acids in HD models, and have potential implications for other pathways modulated by SREBPs, including autophagy and excitotoxicity.


Assuntos
Transporte Ativo do Núcleo Celular , Núcleo Celular/patologia , Colesterol/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Proteína Huntingtina/metabolismo , Proteínas Mutantes/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Animais , Núcleo Celular/metabolismo , Proteínas de Fluorescência Verde/genética , Homeostase , Humanos , Proteína Huntingtina/genética , Camundongos , Proteínas Mutantes/genética , Mutação , Neurônios/metabolismo , Neurônios/patologia , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
12.
Plant Physiol ; 186(3): 1382-1396, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-33826733

RESUMO

About 95% of the ultraviolet (UV) photons reaching the Earth's surface are UV-A (315-400 nm) photons. Plant responses to UV-A radiation have been less frequently studied than those to UV-B (280-315 nm) radiation. Most previous studies on UV-A radiation have used an unrealistic balance between UV-A, UV-B, and photosynthetically active radiation (PAR). Consequently, results from these studies are difficult to interpret from an ecological perspective, leaving an important gap in our understanding of the perception of solar UV radiation by plants. Previously, it was assumed UV-A/blue photoreceptors, cryptochromes and phototropins mediated photomorphogenic responses to UV-A radiation and "UV-B photoreceptor" UV RESISTANCE LOCUS 8 (UVR8) to UV-B radiation. However, our understanding of how UV-A radiation is perceived by plants has recently improved. Experiments using a realistic balance between UV-B, UV-A, and PAR have demonstrated that UVR8 can play a major role in the perception of both UV-B and short-wavelength UV-A (UV-Asw, 315 to ∼350 nm) radiation. These experiments also showed that UVR8 and cryptochromes jointly regulate gene expression through interactions that alter the relative sensitivity to UV-B, UV-A, and blue wavelengths. Negative feedback loops on the action of these photoreceptors can arise from gene expression, signaling crosstalk, and absorption of UV photons by phenolic metabolites. These interactions explain why exposure to blue light modulates photomorphogenic responses to UV-B and UV-Asw radiation. Future studies will need to distinguish between short and long wavelengths of UV-A radiation and to consider UVR8's role as a UV-B/UV-Asw photoreceptor in sunlight.


Assuntos
Criptocromos/fisiologia , Fenômenos Fisiológicos Vegetais , Energia Solar , Raios Ultravioleta
13.
Plant Physiol ; 186(1): 180-192, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-33624812

RESUMO

Tropospheric ozone (O3) is a major air pollutant that decreases yield of important crops worldwide. Despite long-lasting research of its negative effects on plants, there are many gaps in our knowledge on how plants respond to O3. In this study, we used natural variation in the model plant Arabidopsis (Arabidopsis thaliana) to characterize molecular and physiological mechanisms underlying O3 sensitivity. A key parameter in models for O3 damage is stomatal uptake. Here we show that the extent of O3 damage in the sensitive Arabidopsis accession Shahdara (Sha) does not correspond with O3 uptake, pointing toward stomata-independent mechanisms for the development of O3 damage. We compared tolerant (Col-0) versus sensitive accessions (Sha, Cvi-0) in assays related to photosynthesis, cell death, antioxidants, and transcriptional regulation. Acute O3 exposure increased cell death, development of lesions in the leaves, and decreased photosynthesis in sensitive accessions. In both Sha and Cvi-0, O3-induced lesions were associated with decreased maximal chlorophyll fluorescence and low quantum yield of electron transfer from Photosystem II to plastoquinone. However, O3-induced repression of photosynthesis in these two O3-sensitive accessions developed in different ways. We demonstrate that O3 sensitivity in Arabidopsis is influenced by genetic diversity given that Sha and Cvi-0 developed accession-specific transcriptional responses to O3. Our findings advance the understanding of plant responses to O3 and set a framework for future studies to characterize molecular and physiological mechanisms allowing plants to respond to high O3 levels in the atmosphere as a result of high air pollution and climate change.


Assuntos
Antioxidantes/metabolismo , Arabidopsis/fisiologia , Morte Celular/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Ozônio/farmacologia , Fotossíntese/efeitos dos fármacos , Estômatos de Plantas/fisiologia , Arabidopsis/efeitos dos fármacos , Transporte de Elétrons/efeitos dos fármacos , Estômatos de Plantas/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos
14.
J Asthma ; 59(2): 342-351, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33198550

RESUMO

OBJECTIVE: Little is known about the implementation challenges health providers might face with the use of digital health in outpatient asthma care. To qualitatively explore the experience of health providers with electronic medication monitoring (EMM) using an implementation science framework. METHODS: Using the Consolidated Framework of Implementation Research (CFIR), we conducted interviews (n = 10) exploring health providers' experience with EMM with asthma patients from 5 primary care or specialty clinics. The EMM tracked albuterol and inhaled corticosteroid (ICS) use, and health providers called parents whenever ICS adherence waned, or albuterol use increased. Interviews were audio-recorded, transcribed, and deductively analyzed using directed content analysis. RESULTS: Health providers reported the intervention's primary advantage, compared with current asthma care, was the ability to monitor medication use at-home. Most felt the intervention improved care delivery. Nurses and medical assistants described a process of phone calls and checking alerts, that had varying levels of administrative burden and complexity. Health providers felt that sustained implementation of the intervention model would require additional employees to handle the administrative and clinical workload. Half of the interviewed providers were unsure if patient needs were met by the intervention, while some cited technology syncing issues, others liked the enhanced interactions for asthma education. CONCLUSION: Health providers reported positive experiences supporting parents and children with asthma using EMM but also highlighted intervention components that needed improvement or refinement to yield successful implementation in outpatient pediatric clinics. Recommendations for enhancing the intervention for a scaled-up implementation were discussed.


Assuntos
Asma , Pacientes Ambulatoriais , Albuterol , Asma/tratamento farmacológico , Criança , Eletrônica , Humanos , Atenção Primária à Saúde , Pesquisa Qualitativa
15.
Surg Endosc ; 36(2): 1688-1695, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34988740

RESUMO

BACKGROUND: The aim of this study was to quantify Fluorescence angiography with indocyanine green (ICG) in colorectal cancer anastomosis, determine influential factors in its temporary intensity and pattern, assessing the ability to predict the AL, and setting the cut-off levels to establish high- or low-risk groups. METHODS: Retrospective analysis of prospectively managed database, including 70 patients who underwent elective surgery for colorectal cancer in which performing a primary anastomosis was in primary plan. In all of them, ICG fluorescence angiography was performed as usual clinical practice with VisionSense™ VS Iridium (Medtronic, Mansfield, MA, USA), in Elevision™ IR Platform (Medtronic, Mansfield, MA, USA). Parameters measured at real time or calculated were T0, Tmax, ∆T, Fmax, %pos, Fpos, and Slope. RESULTS: 70 patients were included, 69 anastomosis were performed and one end colostomy. Arterial hypertension demonstrated higher Fmax, as well as the location of the anastomosis (the nearest to rectum, the most intensity detected). A statistical relationship was found between AL and the lower Fpos and Slope. The decision of changing the subjectively decided point of division did not demonstrate statistical difference on the further development of AL. All parameters were analyzed to detect the cut-off related with AL. Only in case of Fpos lower than 158.3 U and Slope lower than 13.1 U/s p-value were significant. The most valuable diagnostic parameter after risk stratification was the Negative Predictive Value. CONCLUSION: Quantitative analysis of ICG fluorescence in colorectal surgery is safe and feasible to stratify risk of AL. Hypertension and location of anastomosis influence the intensity of fluorescence at the point of section. A change of division place should be considered to avoid AL related to vascular reasons when intensities of fluorescence at the point of section is lower than 169 U or slopes lower than 14.4 U/s.


Assuntos
Neoplasias Colorretais , Cirurgia Colorretal , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Neoplasias Colorretais/cirurgia , Estudos de Viabilidade , Angiofluoresceinografia , Humanos , Verde de Indocianina , Perfusão , Estudos Retrospectivos
16.
J Med Internet Res ; 24(7): e37233, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35838763

RESUMO

BACKGROUND: Diabetes is a public health problem worldwide. Although diabetes is a chronic and incurable disease, measures and treatments can be taken to control it and keep the patient stable. Diabetes has been the subject of extensive research, ranging from disease prevention to the use of technologies for its diagnosis and control. Health institutions obtain information required for the diagnosis of diabetes through various tests, and appropriate treatment is provided according to the diagnosis. These institutions have databases with large volumes of information that can be analyzed and used in different applications such as pattern discovery and outcome prediction, which can help health personnel in making decisions about treatments or determining the appropriate prescriptions for diabetes management. OBJECTIVE: The aim of this study was to develop a drug recommendation system for patients with diabetes based on collaborative filtering and clustering techniques as a complement to the treatments given by the treating doctor. METHODS: The data set used contains information from patients with diabetes available in the University of California Irvine Machine Learning Repository. Data mining techniques were applied for processing and analysis of the data set. Unsupervised learning techniques were used for dimensionality reduction and patient clustering. Drug predictions were obtained with a user-based collaborative filtering approach, which enabled creating a patient profile that can be compared with the profiles of other patients with similar characteristics. Finally, recommendations were made considering the identified patient groups. The performance of the system was evaluated using metrics to assess the quality of the groups and the quality of the predictions and recommendations. RESULTS: Principal component analysis to reduce the dimensionality of the data showed that eight components best explained the variability of the data. We identified six groups of patients using the clustering algorithm, which were evenly distributed. These groups were identified based on the available information of patients with diabetes, and then the variation between groups was examined to predict a suitable medication for a target patient. The recommender system achieved good results in the quality of predictions with a mean squared error metric of 0.51 and accuracy in the quality of recommendations of 0.61, which is acceptable. CONCLUSIONS: This work presents a recommendation system that suggests medications according to drug information and the characteristics of patients with diabetes. Some aspects related to this disease were analyzed based on the data set used from patients with diabetes. The experimental results with clustering and prediction techniques were found to be acceptable for the recommendation process. This system can provide a novel perspective for health institutions that require technologies to support health care personnel in the management of diabetes treatment and control.


Assuntos
Diabetes Mellitus , Aprendizado de Máquina , Algoritmos , Análise por Conglomerados , Mineração de Dados , Diabetes Mellitus/tratamento farmacológico , Humanos
17.
Int J Mol Sci ; 23(11)2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35682603

RESUMO

Mesothelial cells form the mesothelium, a simple epithelium lining the walls of serous cavities and the surface of visceral organs. Although mesothelial cells are phenotypically well characterized, their immunoregulatory properties remain largely unknown, with only two studies reporting their capacity to inhibit T cells through TGF-ß and their consumption of L-arginine by arginase-1. Whether human mesothelial cells can suppress other immune cells and possess additional leukosuppressive mechanisms, remain to be addressed to better delineate their therapeutic potential for cell therapy. Herein, we generated secretomes from omental mesothelial cells (OMC) and assess their capacity to inhibit lymphocytes proliferation, suppress activated T and B cells, as well as to modify macrophage activation markers. The secretome from mesenchymal stromal cells (MSC) served as a control of immuno-suppression. Although OMC and MSC were phenotypically divergent, their cytokine secretion patterns as well as expression of inflammatory and immunomodulary genes were similar. As such, OMC- and MSC-derived secretomes (OMC-S and MSC-S) both polarized RAW 264.7 macrophages towards a M2-like anti-inflammatory phenotype and suppressed mouse and human lymphocytes proliferation. OMC-S displayed a strong ability to suppress mouse- and human-activated CD19+/CD25+ B cells as compared to MSC-S. The lymphosuppressive activity of the OMC-S could be significantly counteracted either by SB-431542, an inhibitor of TGFß and activin signaling pathways, or with a monoclonal antibody against the TGFß1, ß2, and ß3 isoforms. A strong blockade of the OMC-S-mediated lymphosuppressive activity was achieved using L-NMMA, a specific inhibitor of nitric oxide synthase (NOS). Taken together, our results suggest that OMC are potent immunomodulators.


Assuntos
Imunomodulação , Células-Tronco Mesenquimais , Animais , Humanos , Ativação Linfocitária , Ativação de Macrófagos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Linfócitos T
18.
Physiol Plant ; 173(3): 750-761, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34510478

RESUMO

During recent years, we have advanced our understanding of plant molecular responses to ultraviolet radiation (UV, 280-400 nm); however, how plants respond to UV radiation under different spectral light qualities is poorly understood. In this study, cucumber plants (Cucumis sativus "Lausanna RZ F1") were grown under monochromatic blue, green, red, and broadband white light in combination with UV radiation. The effects of light quality and UV radiation on acclimatory responses were assessed by measuring transcript accumulation of ELONGATED HYPOCOTYL 5 (HY5), CHALCONE SYNTHASE 2 (CHS2), and LIGHT HARVESTING COMPLEX II (LHCII), and the accumulation of flavonoids and hydroxycinnamic acids in the leaves. The growth light backgrounds differentially regulated gene expression and metabolite accumulation. While HY5 and CHS2 transcripts were induced by blue and white light, LHCII was induced by white and red light. Furthermore, UV radiation antagonized the effects of blue, red, green, and white light on transcript accumulation in a gene-dependent manner. Plants grown under blue light with supplementary UV radiation increased phenylalanine, flavonol disaccharide I and caffeic acid contents compared to those exposed only to blue light. UV radiation also induced the accumulation of flavonol disaccharide I and II, ferulic acid hexose and coumaric acid hexose in plants grown under green light. Our findings provide a further understanding of plant responses to UV radiation in combination with different light spectra and contribute to the design of light recipes for horticultural practices that aim to modify plant metabolism and ultimately improve crop quality.


Assuntos
Cucumis sativus , Cucumis sativus/genética , Flavonoides , Hipocótilo , Folhas de Planta , Raios Ultravioleta
19.
Physiol Plant ; 173(3): 666-679, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33948972

RESUMO

Acclimation of plants to water deficit involves biochemical and physiological adjustments. Here, we studied how ultraviolet (UV)-B exposure and exogenously applied hydrogen peroxide (H2 O2 ) potentiates drought tolerance in tobacco (Nicotiana tabacum L. cv. xanthi nc). Separate and combined applications for 14 days of 1.75 kJ m-2  day-1 UV-B radiation and 0.2 mM H2 O2 were assessed. Both factors, individually and combined, resulted in inhibition of growth. Furthermore, the combined treatment led to the most compacted plants. UV-B- and UV-B + H2 O2 -treated plants increased total antioxidant capacity and foliar epidermal flavonol index. H2 O2 - and UV-B + H2 O2 -pre-treated plants showed cross-tolerance to a subsequent 7-day moderate drought treatment, which was assessed as the absence of negative impact on growth, leaf wilting, and leaf relative water content. Plant responses to the pre-treatment were notably different: (1) H2 O2 increased the activity of catalase (EC 1.11.1.6), phenylalanine ammonia lyase (EC 4.3.1.5), and peroxidase activities (EC 1.11.1.7), and (2) the combined treatment induced epidermal flavonols which were key to drought tolerance. We report synergistic effects of UV-B and H2 O2 on transcription accumulation of UV RESISTANCE LOCUS 8, NAC DOMAIN PROTEIN 13 (NAC13), and BRI1-EMS-SUPPRESSOR 1 (BES1). Our data demonstrate a pre-treatment-dependent response to drought for NAC13, BES1, and CHALCONE SYNTHASE transcript accumulation. This study highlights the potential of combining UV-B and H2 O2 to improve drought tolerance which could become a useful tool to reduce water use.


Assuntos
Secas , Nicotiana , Antioxidantes , Peróxido de Hidrogênio , Folhas de Planta
20.
Appl Opt ; 60(5): 1137-1142, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33690562

RESUMO

This paper introduces a novel, to the best of our knowledge, method to estimate and compensate the nonlinear gamma factor introduced by the optical system in fringe projection profilometry. We propose to determine this factor indirectly by adjusting the least-squares plane to the estimated phase coming from the reference plane. We only require a minimal set of three fringe sinusoidal images to estimate the gamma factor. This value can be used to rectify computational legacy data and also to generate and project the new set of fringe patterns for which we perform the inverse gamma compensation. Experimental results demonstrate the feasibility of the proposed method to estimate and correct the gamma distortion.

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