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1.
Mol Biol Rep ; 51(1): 430, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517597

RESUMO

BACKGROUND: Short tandem repeats (STRs) are the most widely used genetic markers in forensic genetics. Therefore, it is essential to document genetic population data of new kits designed for human identification purposes to enable laboratories to use these genetic systems to interpret and solve forensic casework. However, in Mexico, there are no studies with the PowerPlex Fusion 6C System, which includes 26 STRs (23 autosomal STRs and 3 Y-STRs). METHODS AND RESULTS: 600 DNA samples from Mexico City were subjected to genotyping using the PowerPlex Fusion 6C System. For autosomal STRs, 312 different alleles were observed. Combined PE and PD were 99.999999809866% and 99.99999999999999999999999818795%, respectively. Genetic distances and AMOVA test showed low but significant differentiation between Mexican populations. CONCLUSIONS: The results reported in this work demonstrate the efficacy of this system for human identification purposes in the population studied and justify its possible application in other Mexican Mestizo populations.


Assuntos
Impressões Digitais de DNA , Genética Populacional , Humanos , Frequência do Gene/genética , México , Impressões Digitais de DNA/métodos , Repetições de Microssatélites/genética
2.
Eur J Pediatr ; 183(2): 543-555, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37999764

RESUMO

To evaluate milrinone's impact on pediatric cardiac function, focusing on its specific role as an inotrope and lusitrope, while considering its systemic and pulmonary vasodilatory effects. Search of PubMed, EMBASE, and the Cochrane Library up to August 2023. We included all studies that evaluated milrinone in children under 18 years old in neonatal, pediatric, or cardiac intensive care units. We excluded case reports, studies that did not provide tabular information on milrinone's outcomes, and studies focused on non-intensive care populations. We extracted data on the research design, objectives, study sample, and results of each study, including the impact of milrinone and any associated factors. We screened a total of 9423 abstracts and 41 studies were ultimately included. Milrinone significantly improved left ventricular ejection fraction (WMD 3.41 [95% CI 0.61 - 6.21]), left ventricle shortening fraction (WMD 4.25 [95% CI 3.43 - 5.08]), cardiac index (WMD 0.50 [95% CI 0.32 to 0.68]), left ventricle output (WMD 55.81 [95% CI 4.91 to 106.72]), serum lactate (WMD -0.59 [95% CI -1.15 to -0.02]), and stroke volume index (WMD 2.95 [95% CI 0.09 - 5.82]). However, milrinone was not associated with improvements in ventricular myocardial performance index (WMD -0.01 [95% CI -0.06 to 0.04]) and ventricular longitudinal strain (WMD -2.14 [95% CI -4.56 to 0.28]). Furthermore, milrinone was not associated with isovolumetric relaxation time reduction (WMD -8.87 [95% CI -21.40 to 3.66]). CONCLUSION: Our meta-analysis suggests potential clinical benefits of milrinone by improving cardiac function, likely driven by its systemic vasodilatory effects. However, questions arise about its inotropic influence and the presence of a lusitropic effect. Moreover, milrinone's pulmonary vasodilatory effect appears relatively weaker compared to its systemic actions. Further research is needed to elucidate milrinone's precise mechanisms and refine its clinical applications in pediatric practice. WHAT IS KNOWN: • Milrinone is a phosphodiesterase III inhibitor that has been used to treat a variety of pediatric and neonatal conditions. • Milrinone is believed to exert its therapeutic effects by enhancing cardiac contractility and promoting vascular relaxation. WHAT IS NEW: • Milrinone may not have a significant inotropic effect. • Milrinone's pulmonary vasodilatory effect is less robust than its systemic vasodilatory effect.


Assuntos
Insuficiência Cardíaca , Hipertensão Pulmonar , Adolescente , Criança , Humanos , Recém-Nascido , Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Hipertensão Pulmonar/tratamento farmacológico , Milrinona/uso terapêutico , Volume Sistólico , Função Ventricular Esquerda , Lactente , Pré-Escolar
3.
Int J Mol Sci ; 24(24)2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38139013

RESUMO

Here, we report the in-host hepatitis E virus (HEV) quasispecies evolution in a chronically infected patient who was treated with three different regimens of ribavirin (RBV) for nearly 6 years. Sequential plasma samples were collected at different time points and subjected to RNA extraction and deep sequencing using the MiSeq Illumina platforms. Specifically, we RT-PCR amplified a single amplicon from the core region located in the open-reading frame 2 (ORF2). At the nucleotide level (genotype), our analysis showed an increase in the number of rare haplotypes and a drastic reduction in the frequency of the master (most represented) sequence during the period when the virus was found to be insensitive to RBV treatment. Contrarily, at the amino acid level (phenotype), our study revealed conservation of the amino acids, which is represented by a high prevalence of the master sequence. Our findings suggest that using mutagenic antivirals concomitant with high viral loads can lead to the selection and proliferation of a rich set of synonymous haplotypes that express the same phenotype. This can also lead to the selection and proliferation of conservative substitutions that express fitness-enhanced phenotypes. These results have important clinical implications, as they suggest that using mutagenic agents as a monotherapy treatment regimen in the absence of sufficiently effective viral inhibitors can result in diversification and proliferation of a highly diverse quasispecies resistant to further treatment. Therefore, such approaches should be avoided whenever possible.


Assuntos
Antivirais , Vírus da Hepatite E , Humanos , Antivirais/farmacologia , Antivirais/uso terapêutico , Vírus da Hepatite E/genética , Mutagênicos , Quase-Espécies/genética , Ribavirina/farmacologia , Ribavirina/uso terapêutico
4.
J Microsc ; 286(1): 22-30, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35092003

RESUMO

Raman spectroscopy, transmission electron microscopy (TEM) and atomic force microscopy (AFM) techniques can perform chemical analyses and acquire high-resolution images of cell samples. For this reason, in this study, semi-thin sections of a single Penicillium rubens cell were analysed by Raman enhanced surface spectroscopy. The spectra showed peaks corresponding to the macromolecules that make up the cellular components. In addition, the various organelles were analysed by TEM and AFM to observe the cellular nanostructures. With the use of these techniques, it is possible to identify molecules in semi-thin sections, which provides a wide potential for biomedical applications and for the analysis of cell dynamics. The observation of the most detailed possible structure of cells is used as a starting point in numerous studies to identify and localise some biochemical processes. Given that the function of eukaryotic cells depends on the location, shape, structure and function of the subcellular organelles (and on the interaction between them), the sum of the data obtained allows a complete analysis of what happens in the cell. This article addresses, from a multidisciplinary point of view, what happens in a single cell of a filamentous fungus (Penicillium rubens) while it is in a physiological moment (secondary metabolism) that allows the biosynthesis of an antibiotic (penicillin). For this purpose, different types of microscopies were used (TEM: transmission electron microscopy, and AFM: atomic force microscopy, which allow visualising small details in the cell) and a spectroscopy method (Raman, which allows detecting certain characteristics of the macromolecules and some stretching bonds). Regarding the results, during the synthesis of penicillin, the antibiotic-producing Penicillium rubens cells showed significant changes compared to the non-producing cells: the cell wall is observed to be significantly thickened in the production phase, organelles such as peroxisomes grow in number and size since it is known that the final route of metabolite synthesis takes place in them. When penicillin is released from peroxisomes, they must be degraded to release the load from the cell; this is done by vacuoles, which are active and engulf peroxisomes. The newly synthesised penicillin is found within secretory vesicles that travel towards the cell membrane and both membranes fuse creating ripples. On the other hand, and given that a single cell is being studied, it is essential to increase the signal to detect biomolecules employing the Raman-SERS technique, using a silver substrate to obtain the increased signal.


Assuntos
Penicilinas , Penicillium , Antibacterianos/metabolismo , Penicilinas/metabolismo , Penicillium/metabolismo , Penicillium/ultraestrutura , Análise Espectral Raman
5.
Int J Mol Sci ; 23(23)2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36498981

RESUMO

The changes occurring in viral quasispecies populations during infection have been monitored using diversity indices, nucleotide diversity, and several other indices to summarize the quasispecies structure in a single value. In this study, we present a method to partition quasispecies haplotypes into four fractions according to their fitness: the master haplotype, rare haplotypes at two levels (those present at <0.1%, and those at 0.1−1%), and a fourth fraction that we term emerging haplotypes, present at frequencies >1%, but less than that of the master haplotype. We propose that by determining the changes occurring in the volume of the four quasispecies fitness fractions together with those of the Hill number profile we will be able to visualize and analyze the molecular changes in the composition of a quasispecies with time. To develop this concept, we used three data sets: a technical clone of the complete SARS-CoV-2 spike gene, a subset of data previously used in a study of rare haplotypes, and data from a clinical follow-up study of a patient chronically infected with HEV and treated with ribavirin. The viral response to ribavirin mutagenic treatment was selection of a rich set of synonymous haplotypes. The mutation spectrum was very complex at the nucleotide level, but at the protein (phenotypic/functional) level the pattern differed, showing a highly prevalent master phenotype. We discuss the putative implications of this observation in relation to mutagenic antiviral treatment.


Assuntos
Vírus da Hepatite E , Hepatite E , Ribavirina , Humanos , Seguimentos , Mutagênicos , Nucleotídeos , Quase-Espécies/genética , Ribavirina/uso terapêutico , SARS-CoV-2/genética , Hepatite E/tratamento farmacológico , Vírus da Hepatite E/efeitos dos fármacos , Vírus da Hepatite E/genética
6.
Cell Physiol Biochem ; 55(S2): 1-12, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33398982

RESUMO

BACKGROUND/AIMS: Lung carcinoids are uncommon neuroendocrine tumours. Molecular features of lung carcinoids have been poorly defined. microRNAs (miRNAs) are potent gene expression regulators with important roles in cancer development and progression. However, little is known on the role of miRNAs in the pathogenesis of lung carcinoids. Our goals were to identify commonly deregulated miRNAs in a rare case of lung carcinoid of typical histology with metastasis, as well as map miRNA target genes in pathways potentially associated with disease development and progression. METHODS: miRNA expression profiles were assessed using the TaqMan Low Density Arrays, which is a platform including 384 miRNAs. miRNA profiles were generated in the tumor and its corresponding lymph node metastasis, compared to reference normal lung tissues. Furthermore, miRNA expression was validated in a separate, publicly available external dataset (n=19 typical lung carcinoids; 2/19 were metastatic tumors, compared to six normal lung tissues, GSE77380). Following this analysis, computational tools were applied for data interpretation. miRTarBase was used to determine miRNA-target genes, followed by ToppGene Suite analysis to identify pathways and biological functions. In addition, the expression of genes targeted by miRNAs was validated in a second, separate external dataset (n=13 tumour samples, GSE35679). GEO2R data analysis tool was used in both validation analyses (miRNAs and genes). RESULTS: We identified 15 commonly significantly downregulated miRNAs (fold change, FC≥2 and p<0.05) in the tumour and its paired metastasis, with further decreasing levels in the metastatic lesion. Downregulation of miR-126-3p and miR-146b-5p was validated in the external dataset GSE77380. In addition, SOX2 and TCF4 genes, targeted by miR-126-3p, were consistently overexpressed in a subset of six typical lung carcinoids from the external dataset GSE35679. Pathways analysis showed that miRNAs miR-126-3p and miR-146b-5p target genes with a role in the regulation of adaptive immune response. CONCLUSION: Our results contribute to the identification of miRNA expression changes in a typical lung carcinoid and its corresponding lymph node metastasis. Down-regulated levels of miR-126-3p and miR-146b-5p and target gene over-expression could play a role in the progression of this case of primary typical lung carcinoid to regional metastasis. Identified miRNAs and target genes are potential candidates for validation in a larger number of cases.


Assuntos
Tumor Carcinoide/genética , Tumor Carcinoide/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , MicroRNAs/imunologia , Imunidade Adaptativa/genética , Adulto , Biomarcadores Tumorais/genética , Tumor Carcinoide/patologia , Biologia Computacional/métodos , Feminino , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , MicroRNAs/genética , Estadiamento de Neoplasias
7.
J Viral Hepat ; 28(9): 1319-1324, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33720484

RESUMO

Direct-acting antivirals (DAAs) resolve chronic HCV infection in >95% of patients, but a small percentage do not respond to DAA-based therapy. These may be difficult to treat because of resistance-associated substitutions (RAS) emerging after treatment failure. Triple therapy with sofosbuvir (SOF)/velpatasvir (VEL)/voxilaprevir (VOX) is the recommended retreatment after DAA-based failure. However, in rare cases, failure to triple therapy occurs, and there is little information characterizing the viruses that relapse. To determine the RAS profile after failing SOF/VEL/VOX, and seek suitable alternatives for retreatment, samples from 5 patients were analysed using MiSeq Illumina deep sequencing before and after triple therapy. All patients were men, aged 59-78 years, 2 HCV genotype (G) 1b and 3 G3a. The most prevalent NS3 substitutions after SOF/VEL/VOX failure were Y56F and A166T. Four patients had the NS5A RAS, Y93H, after triple failure, and Y93H was observed in both G1b patients before retreatment and after SOF/ledipasvir failure. In 2 G3a patients, Y93H appeared at triple failure, and on the other G3a, A30K persisted in 100% of viral genomes. Finally, G1b patients showed C316N in NS5B, associated with SOF failure, but G3a patients had no known NS5B substitutions. HCV RAS analysis identified the following substitutions present at higher rates after triple failure: Y56F in NS3 (G1b), A166T in NS3 (G3a), A30K or Y93H in NS5A, and C316N in NS5B (G1b). A RAS-based salvage treatment (SOF + glecaprevir/pibrentasvir + RBV) was successfully used in one G3a patient.


Assuntos
Hepatite C Crônica , Sofosbuvir , Idoso , Ácidos Aminoisobutíricos , Antivirais/uso terapêutico , Carbamatos , Ciclopropanos , Farmacorresistência Viral , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Prolina/análogos & derivados , Quinoxalinas , Sofosbuvir/uso terapêutico , Sulfonamidas , Falha de Tratamento , Proteínas não Estruturais Virais/genética
8.
Clin Oral Investig ; 25(4): 1767-1774, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32748074

RESUMO

OBJECTIVE: To investigate the efficacy of sclerotherapy with monoethanolamine oleate (MEO) in a series of cases of benign oral vascular lesions (BOVL). MATERIAL AND METHODS: Clinical records and images were retrieved (2015-2019), and data regarding age, gender, location, size, symptomatology, treatment and outcomes of patients were collected. All patients were diagnosed according to the classification of International Society for the Study of Vascular Anomalies and received the same treatment protocol (MEO 0.05 g/mL). The collected data were submitted to descriptive analysis and Pearson's chi-square test (p ≤ 0.05). RESULTS: Thirty-seven patients were treated. Most were female (70.3%) aged 9 to 88 years (median, 57.5 ± 17.4 years). Lower lip (54.1%) was the most affected site followed by buccal mucosa (16.2%). Thirty-two lesions were asymptomatic and 35.1% showed ≤ 0.5 cm in size. In 48.6% of the patients, only one application of MEO was performed. Complete regression occurred in 62.2% of cases, whereas 27% showed partial regression. One patient showed hypersensitivity during treatment. There was no significant difference between clinical outcome and age, anatomic site, size, and number of applications of MEO. CONCLUSIONS: Sclerotherapy with MEO is an acceptable and affordable treatment and can provide satisfactory results in BOVL, especially where other treatment options could compromise the esthetic aspects. CLINICAL RELEVANCE: As it is a non-invasive therapy leading, in most cases, to adequate clinical results, safety, and tolerability, sclerotherapy with MEO can be considered an effective treatment for BOVL.


Assuntos
Escleroterapia , Malformações Vasculares , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estética Dentária , Feminino , Humanos , Pessoa de Meia-Idade , Ácidos Oleicos , Soluções Esclerosantes/uso terapêutico , Resultado do Tratamento , Malformações Vasculares/tratamento farmacológico , Adulto Jovem
9.
Molecules ; 26(3)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33572779

RESUMO

Plants have been used for thousands of years for various purposes because they have a wide variety of activities with biological significance. Mexican oregano is an aromatic plant of great importance to Mexico and north of Jalisco state as a spice with important economic value. Chromatographic identification and quantification of phenolic compounds and evaluation of their antioxidant activity were important tools to obtain a better characterization of this spice. Phytochemical analysis indicated the presence of flavonoids, triterpenes, saponins, quinones and tannins, the latter at high concentrations. Through chromatographic assays of Mexican oregano extracts, 62 compounds were identified, the major ones being quantified as: taxifolin, apigenin 7-O-glucoside, phlorizin, eriodictyol, quercetin, naringenin, hispidulin, pinocembrin, galangin and genkwanin (compound for the first time reported for this species). The results can be useful as a precedent to establish the bases of new quality characterization parameters and they have also suggested that Mexican oregano contains a wide variety of compounds with untapped importance for the development of new high value-added products.


Assuntos
Antioxidantes/química , Origanum/química , Fenóis/química , Flavonoides/química , Humanos , Fenóis/classificação , Fenóis/isolamento & purificação , Extratos Vegetais/química , Quinonas/química , Saponinas/química , Taninos/química , Triterpenos/química
10.
Reprod Domest Anim ; 55(1): 38-43, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31646687

RESUMO

Nellore is the main cattle breed used in Brazil, being the largest commercial herd in the world. Beyond the importance of male reproductive efficiency for farm profit, the use of reproductive techniques, mainly artificial insemination, turns the evaluation of male reproductive traits even more important. Estimation of genetic parameters increases the knowledge on traits variances and allows envisaging the possibility of the inclusion of new traits as selection criterion. Genetic parameters for fifteen traits that can be classified as testicular biometry or physical and morphological semen traits were estimated for a Nellore bull population ranging from 18 to 36 months. Single-trait and bi-trait animal models were used for (co)variance components estimation. The contemporary group was considered as fixed effect and age at measurement as covariable. Scrotal circumference presented heritability of 0.47 ± 0.12. This value is similar to the heritabilities found for all testicular biometry traits (0.34-0.48). Sperm progressive motility, which has a direct effect on bull fertility, presented low heritability (0.07 ± 0.08). Major and total sperm defects presented moderate to high heritabilities (0.49 ± 0.18 and 0.39 ± 0.15, respectively), indicating that great genetic gain can be obtained through selection against sperm defects. High and positive genetic correlations were observed among testicular biometry traits, which also presented favourable genetic correlations with physical and morphological traits of the semen with magnitude ranging from high to low. Scrotal circumference presented moderate to high and favourable genetic correlations with sperm progressive motility, sperm turbulence, major sperm defects and total sperm defects. Thus, the selection for scrotal circumference results in favourable correlated genetic response for semen quality. The results show that the use of scrotal circumference as reference trait for bull fertility is appropriate, since it presents high heritability and favourable genetic correlation with semen quality.


Assuntos
Bovinos/genética , Fertilidade/genética , Testículo/anatomia & histologia , Animais , Cruzamento , Bovinos/anatomia & histologia , Masculino , Característica Quantitativa Herdável , Escroto/anatomia & histologia , Análise do Sêmen/veterinária , Motilidade dos Espermatozoides/genética , Espermatozoides/anormalidades
11.
J Sci Food Agric ; 100(8): 3536-3543, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32240539

RESUMO

BACKGROUND: Vitamin A has been reported as a factor influencing marbling deposition in meat from animals. Although the mechanisms by which vitamin A regulates lipid metabolism in mature adipocytes are already well-established, information regarding molecular mechanisms underlying the effects of vitamin A on the regulation of intramuscular fat deposition in beef cattle still remains limited. The present study aimed to assess the molecular mechanisms involved in the intramuscular fat deposition in beef cattle supplemented with vitamin A during the fattening phase using a proteomic approach. RESULTS: Vitamin A supplementation during the fattening phase decreased intramuscular fat deposition in beef cattle. Proteome and phospho-proteome analysis together with biological and networking analysis of the protein differentially abundant between treatments indicated that Vitamin A supplementation affects the overall energy metabolism of skeletal muscle, impairing lipid biosynthesis in skeletal muscle. CONCLUSION: Vitamin A supplementation at fattening phase impairs intramuscular fat deposition in beef cattle likely by changing the energy metabolism of skeletal muscle. The interaction of retinoic acid and heat shock 70-kDa protein may play a pivotal role in intramuscular fat deposition as a consequence of vitamin A supplementation by impairing de novo fatty acid synthesis as a result of a possible decrease in insulin sensitivity in the skeletal muscle. © 2020 Society of Chemical Industry.


Assuntos
Bovinos/metabolismo , Carne/análise , Músculo Esquelético/química , Vitamina A/metabolismo , Ração Animal/análise , Animais , Suplementos Nutricionais/análise , Metabolismo Energético , Ácidos Graxos/análise , Ácidos Graxos/biossíntese , Lipogênese , Músculo Esquelético/metabolismo , Proteômica , Vitamina A/administração & dosagem
12.
Viruses ; 16(5)2024 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-38793592

RESUMO

In quasispecies diversity studies, the comparison of two samples of varying sizes is a common necessity. However, the sensitivity of certain diversity indices to sample size variations poses a challenge. To address this issue, rarefaction emerges as a crucial tool, serving to normalize and create fairly comparable samples. This study emphasizes the imperative nature of sample size normalization in quasispecies diversity studies using next-generation sequencing (NGS) data. We present a thorough examination of resampling schemes using various simple hypothetical cases of quasispecies showing different quasispecies structures in the sense of haplotype genomic composition, offering a comprehensive understanding of their implications in general cases. Despite the big numbers implied in this sort of study, often involving coverages exceeding 100,000 reads per sample and amplicon, the rarefaction process for normalization should be performed with repeated resampling without replacement, especially when rare haplotypes constitute a significant fraction of interest. However, it is noteworthy that different diversity indices exhibit distinct sensitivities to sample size. Consequently, some diversity indicators may be compared directly without normalization, or instead may be resampled safely with replacement.


Assuntos
Variação Genética , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Quase-Espécies , Vírus , Quase-Espécies/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Vírus/genética , Vírus/classificação , Vírus/isolamento & purificação , Genoma Viral , Humanos , Genômica/métodos , Filogenia , Tamanho da Amostra
13.
Leg Med (Tokyo) ; 66: 102344, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37977100

RESUMO

Allele frequencies and forensic parameters for 21 STR autosomal markers (CSF1PO, D10S1248, D12S391, D13S317,D16S539, D18S51, D19S433, D1S1656,D21S11, D22S1045, D2S1338, D2S441, D3S1358, D5S818, D7S820, D8S1179, FGA, SE33, TH01, TPOX and vWA) were reported in 289 unrelated individuals from Mexico City, Mexico. In addition, an interpopulation analysis was performed including other world populations. In brief, the established population database of 21 autosomal STR markers in the present work is adequate for human identification purposes.


Assuntos
Genética Populacional , Repetições de Microssatélites , Humanos , México , Repetições de Microssatélites/genética , Impressões Digitais de DNA , Frequência do Gene
14.
bioRxiv ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38585881

RESUMO

Standard chow diet contributes to reproducibility in animal model experiments since chows differ in nutrient composition, which can independently influence phenotypes. However, there is little evidence of the role of timing in the extent of variability caused by chow exposure. Here, we measured the impact of diet (5V5M, 5V0G, 2920X, and 5058) and timing of exposure (adult exposure (AE), lifetime exposure (LE), and developmental exposure (DE)) on growth & development, metabolic health indicators, and gut bacterial microbiota profiles across genetically identical C57BL6/J mice. Diet drove differences in macro- and micronutrient intake for all exposure models. AE had no effect on measured outcomes. However, LE mice exhibited significant sex-dependent diet effects on growth, body weight, and body composition. LE effects were mostly absent in the DE model, where mice were exposed to chow differences from conception to weaning. Both AE and LE models exhibited similar diet-driven beta diversity profiles for the gut bacterial microbiota, with 5058 diet driving the most distinct profile. Diet-induced beta diversity profiles were sex-dependent for LE mice. Compared to AE, LE drove 9X more diet-driven differentially abundant genera, majority of which were the result of inverse effects of 2920X and 5058. Our findings demonstrate that lifetime exposure to different chow diets has the greatest impact on reproducibility of experimental measures that are common components of preclinical mouse model studies. Importantly, weaning DE mice onto a uniform diet is likely an effective way to reduce unwanted phenotypic variability among experimental models.

15.
Microorganisms ; 12(5)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38792840

RESUMO

The repeated failure to treat patients chronically infected with hepatitis E (HEV) and C (HCV) viruses, despite the absence of resistance-associated substitutions (RAS), particularly in response to prolonged treatments with the mutagenic agents of HEV, suggests that quasispecies structure may play a crucial role beyond single point mutations. Quasispecies structured in a flat-like manner (referred to as flat-like) are considered to possess high average fitness, occupy a significant fraction of the functional genetic space of the virus, and exhibit a high capacity to evade specific or mutagenic treatments. In this paper, we studied HEV and HCV samples using high-depth next-generation sequencing (NGS), with indices scoring the different properties describing flat-like quasispecies. The significance of these indices was demonstrated by comparing the values obtained from these samples with those from acute infections caused by respiratory viruses (betacoronaviruses, enterovirus, respiratory syncytial viruses, and metapneumovirus). Our results revealed that flat-like quasispecies in HEV and HCV chronic infections without RAS are characterized by numerous low-frequency haplotypes with no dominant one. Surprisingly, these low-frequency haplotypes (at the nucleotide level) exhibited a high level of synonymity, resulting in much lower diversity at the phenotypic level. Currently, clinical approaches for managing flat-like quasispecies are lacking. Here, we propose methods to identifying flat-like quasispecies, which represents an essential initial step towards exploring alternative treatment protocols for viruses resistant to conventional therapies.

16.
J Clin Med ; 12(4)2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36836204

RESUMO

OBJECTIVE: The objective of this study is to define the real-life clinical profile and therapeutic management of patients with idiopathic pulmonary fibrosis using artificial intelligence. METHODS: We have conducted an observational, retrospective, non-interventional study using data from the Castilla-La Mancha Regional Healthcare Service (SESCAM) in Spain between January 2012 and December 2020. The Savana Manager 3.0 artificial intelligence platform was used to collect information from electronic medical records by applying natural language processing. RESULTS: Our study includes 897 subjects whose diagnosis was compatible with idiopathic pulmonary fibrosis; 64.8% were men, with a mean age of 72.9 years (95% CI 71.9-73.8), and 35.2% were women, with a mean age of 76.8 years (95% CI 75.5-78). Patients who had a family history of IPF (98 patients; 12%) were younger and predominantly female (53.1%). Regarding treatment, 45% of patients received antifibrotic therapy. Patients who had undergone lung biopsy, chest CT, or bronchoscopy were younger than the patient population in whom these studies were not completed. CONCLUSIONS: This study has used artificial intelligence techniques to analyze a large population over a 9-year period and determine the situation of IPF in standard clinical practice by identifying the patient clinical profile, use of diagnostic tests and therapeutic management.

17.
Arch Bronconeumol ; 59(12): 797-804, 2023 Dec.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37734964

RESUMO

INTRODUCTION: Herpes zoster (HZ) is a condition that results from the reactivation of the varicella zoster virus (VZV). Several diseases have been reported to increase the risk of developing HZ and postherpetic neuralgia (PHN). The objective of this study is to analyze the prevalence and risk factors for HZ and PHN in the most frequent chronic respiratory diseases, which are chronic obstructive pulmonary disease (COPD), asthma, lung cancer and obstructive sleep apnea (OSA). METHODS: We conducted an observational, retrospective, non-interventional study between January 2012 and December 2020 based on data from the Castilla-La Mancha Regional Health System in Spain. We used the Savana Manager 3.0 artificial intelligence-enabled system to collect information from electronic medical records. RESULTS: 31765 subjects presented a diagnosis of HZ. Mean age was 64.5 years (95%CI 64.3-64.7), and 58.2% were women. The prevalence of HZ showed an increasing trend in patients over the age of 50. A risk analysis adjusted for sex and comorbidities in COPD, asthma, lung cancer and OSA presented a higher risk of developing HZ in the first three (OR 1.16 [95%CI 1.13-1.19], 1.67 [1.63-1.71], 1.68 [1.60-1.76], respectively), which further increased in all three when associated with comorbidities. Regarding postherpetic neuralgia, an increased risk was only observed related to COPD and lung cancer (OR 1.24 [95%CI 1.23-1.25], 1.14 [1.13-1.16], respectively), further increasing when associated with comorbidities. CONCLUSIONS: In a standard clinical practice setting, the most prevalent respiratory diseases (asthma, COPD and lung cancer) are related to a higher risk of HZ and PHN. These data are fundamental to assess the potential impact of vaccination in this population.


Assuntos
Asma , Herpes Zoster , Neoplasias Pulmonares , Neuralgia Pós-Herpética , Doença Pulmonar Obstrutiva Crônica , Apneia Obstrutiva do Sono , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Neuralgia Pós-Herpética/etiologia , Neuralgia Pós-Herpética/complicações , Estudos Retrospectivos , Inteligência Artificial , Herpes Zoster/complicações , Herpes Zoster/epidemiologia , Fatores de Risco , Herpesvirus Humano 3 , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Asma/epidemiologia , Asma/complicações , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/complicações , Apneia Obstrutiva do Sono/complicações
18.
J Pers Med ; 13(12)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38138856

RESUMO

BACKGROUND: We aimed to analyze the impact of the COVID-19 pandemic on pulmonary tuberculosis (TB) using artificial intelligence. To do so, we compared the real-life situation during the pandemic with the pre-2020 situation. METHODS: This non-interventional, retrospective, observational study applied natural language processing to the electronic health records of the Castilla-La Mancha region of Spain. The analysis was conducted from January 2015 to December 2020. RESULTS: A total of 2592 patients were diagnosed with pulmonary tuberculosis; 64.6% were males, and the mean age was 53.5 years (95%CI 53.0-54.0). In 2020, pulmonary tuberculosis diagnoses dropped by 28% compared to 2019. In total, 62 (14.2%) patients were diagnosed with COVID-19 and pulmonary tuberculosis coinfection in 2020, with a mean age of 52.3 years (95%CI 48.3-56.2). The main symptoms in these patients were dyspnea (27.4%) and cough (35.5%), although their comorbidities were no greater than patients with isolated TB. The female sex was more frequently affected, representing 53.4% of this patient subgroup. CONCLUSIONS: During the first year of the COVID-19 pandemic, a decrease was observed in the incidence of pulmonary tuberculosis. Women presented a significantly higher risk for pulmonary tuberculosis and COVID-19 coinfection, although the symptoms were not more severe than patients diagnosed with pulmonary tuberculosis alone.

19.
Mar Pollut Bull ; 187: 114503, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36608473

RESUMO

We analyzed fish eggs and larvae in an estuary under severe drought conditions. We detected an inverse salinity gradient, with values increasing from the mouth to the upper estuary. Egg densities decreased from the estuarine mouth to the upstream areas following the salinity increase for all three mesh net sizes. This pattern was also found for the density of larvae, which decreased in estuarine regions with hypersalinity (38 to 62). The low diversity constituted only nine fish species, which were classified as anadromous (Anchoa hepsetus), estuarine and marine (Bathygobius soporator, Hippocampus reidi, Eucinostomus sp., and Diapterus auratus), marine estuarine-opportunist (Caranx latus and Bardiella rochus), and marine stragglers (Echeneis naucrates and Haemulon sp.). In addition, we observed an oversimplification of the assemblage to include stress-tolerant estuarine and marine species. Our baseline results suggest that this hypersaline estuarine ecosystem has lower densities and diversity than a healthy mangrove system.


Assuntos
Ecossistema , Perciformes , Animais , Larva , Estuários , Secas , Peixes
20.
J Biophotonics ; 16(2): e202200363, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36529999

RESUMO

Organ transplantations have an increasing medical relevance. It is becoming a regular procedure with an increase in individuals waiting for organs. The increase in the number of discarded organs is mostly due to the donor's bacterial and/or viral infection. In this article, we are demonstrating the feasibility of reduction of the bacterial load in the kidney model by using Ultraviolet-C (UV-C) as a germicidal agent in circulating liquids. Using Staphylococcus aureus as a bacteria model, we were able to demonstrate that in less than 30 min of liquid circulation and associated to irradiation, the bacterial load of the perfusate Custodiol® HTK, histidine-tryptophan-ketoglutarate (solution with 5 log CFU ml-1 ), was fully eliminated. A modeling approach was created to verify the possibility of bacterial load decrease, when an organ (here, a renal experimental model) is present in the circuit, releasing a varied rate of microorganisms over time, while the solution is irradiated. Finally, we use an ex vivo model with a swine kidney, circulating in the preservation solution with a Lifeport® Kidney Transporter machine, to demonstrate that we can contaminate the organ and then promote the elimination of the microbiological load. The results show the feasibility of the technique.

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