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1.
Respiration ; 103(5): 275-279, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38471472

RESUMEN

INTRODUCTION: The use of cryobiopsy in conjunction with robotic assisted bronchoscopy is on the rise due to the safety and increased diagnostic yield of cryobiopsy. The incorporation of 3D fluoroscopy in the procedure improves the workflow and helps confirm the accuracy of sampling of peripheral pulmonary nodules. METHODS: We describe an observational series of 12 patients comprising 14 nodules where cryobiopsy was performed during shape-sensing robot-assisted bronchoscopy cryobiopsy under general anesthesia. 3D fluoroscopy was used to confirm accurate placement of the cryoprobe. All these patients underwent a second spin with the 3D fluoroscopy either to sample a second lesion intraoperatively or to investigate suspected pneumothorax. RESULTS: The development of a pneumatocele was noted after cryobiopsy in each of the cases. The majority of these were in the upper lobe with the median size of a sampled nodule being 14 mm. The majority of patients were asymptomatic with 1 patient developing mild hemoptysis and 4 patients developing chest tightness or dyspnea. None of the patients required an intervention for the pneumatocele. CONCLUSION: The development of pneumatoceles appears to be a fairly frequent and benign occurrence following cryobiopsy, likely due to increased tissue destruction. The increased use of intraoperative 3D fluoroscopy is likely to highlight changes to the pulmonary parenchyma that were previously not known. The occurrence of pneumatoceles does not appear to adversely impact the safety or tolerability profile of cryobiopsy.


Asunto(s)
Broncoscopía , Criocirugía , Procedimientos Quirúrgicos Robotizados , Humanos , Broncoscopía/métodos , Broncoscopía/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Anciano , Fluoroscopía , Procedimientos Quirúrgicos Robotizados/métodos , Criocirugía/métodos , Criocirugía/efectos adversos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico , Biopsia/métodos , Biopsia/efectos adversos , Biopsia/instrumentación , Quistes/patología , Quistes/diagnóstico , Adulto
2.
Respiration ; 103(7): 397-405, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38648757

RESUMEN

INTRODUCTION: The widespread use of computed tomography as a screening tool for early lung cancer has increased detection of pulmonary lesions. It is common to encounter patients with more than one peripheral pulmonary nodule (PPN) of uncertain etiology. Shape-sensing robotic-assisted bronchoscopy (ssRAB) emerges as a potential alternative to biopsy multiple PPN, in addition to mediastinal staging in single anesthetic procedure. METHODS: This is a single-center, retrospective review of 22 patients who underwent ssRAB for evaluation of two or more PPN, between November 2021 and April 2023 at Mayo Clinic, FL, USA. RESULTS: A total of 46 PPNs were biopsied in 22 patients. All lesions were ≤2 cm with a median minimum and maximum cross-sectional lesion size of 1.40 cm and 1.05 cm, respectively. Diagnostic yield was 86.9% (n = 40), and target reach was 91.3% (n = 42). Most lesions were in the upper lobes, a solid pattern was found in 78.3% (n = 36), bronchus sign was present in 82.6% of cases (n = 38), 54.4% (n = 25) were malignant nodules, and 32.6% (n = 15) were benign. Fourteen patients had at least one malignant lesion out of two or more nodules sampled, and 10 patients had a malignant diagnosis for all sampled lesions. The complication rate was 9% (n = 2) with one case of bleeding and one of pneumothorax. CONCLUSION: This study is, to our knowledge, the first to assess the use and safety of ssRAB for diagnosis of multiple PPN in a single anesthetic event. This procedure will mainly impact management decisions and subsequently shorten the time from diagnosis to treatment.


Asunto(s)
Broncoscopía , Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Procedimientos Quirúrgicos Robotizados , Humanos , Broncoscopía/métodos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Procedimientos Quirúrgicos Robotizados/métodos , Nódulos Pulmonares Múltiples/patología , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/diagnóstico , Nódulos Pulmonares Múltiples/cirugía , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Tomografía Computarizada por Rayos X , Adulto
3.
Respiration ; 103(5): 280-288, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38471496

RESUMEN

INTRODUCTION: Lung cancer remains the leading cause of cancer death worldwide. Subsolid nodules (SSN), including ground-glass nodules (GGNs) and part-solid nodules (PSNs), are slow-growing but have a higher risk for malignancy. Therefore, timely diagnosis is imperative. Shape-sensing robotic-assisted bronchoscopy (ssRAB) has emerged as reliable diagnostic procedure, but data on SSN and how ssRAB compares to other diagnostic interventions such as CT-guided transthoracic biopsy (CTTB) are scarce. In this study, we compared diagnostic yield of ssRAB versus CTTB for evaluating SSN. METHODS: A retrospective study of consecutive patients who underwent either ssRAB or CTTB for evaluating GGN and PSN with a solid component less than 6 mm from February 2020 to April 2023 at Mayo Clinic Florida and Rochester. Clinicodemographic information, nodule characteristics, diagnostic yield, and complications were compared between ssRAB and CTTB. RESULTS: A total of 66 nodules from 65 patients were evaluated: 37 PSN and 29 GGN. Median size of PSN solid component was 5 mm (IQR: 4.5, 6). Patients were divided into two groups: 27 in the ssRAB group and 38 in the CTTB group. Diagnostic yield was 85.7% for ssRAB and 89.5% for CTTB (p = 0.646). Sensitivity for malignancy was similar between ssRAB and CTTB (86.4% vs. 88.5%; p = 0.828), with no statistical difference. Complications were more frequent in CTTB with no significant difference (8 vs. 2; p = 0.135). CONCLUSION: Diagnostic yield for SSN was similarly high for ssRAB and CTTB, with ssRAB presenting less complications and allowing mediastinal staging within the same procedure.


Asunto(s)
Broncoscopía , Biopsia Guiada por Imagen , Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Procedimientos Quirúrgicos Robotizados , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Broncoscopía/métodos , Anciano , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagen , Biopsia Guiada por Imagen/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Nódulos Pulmonares Múltiples/patología , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/diagnóstico , Nódulo Pulmonar Solitario/patología , Nódulo Pulmonar Solitario/diagnóstico por imagen , Nódulo Pulmonar Solitario/diagnóstico
4.
Nucleic Acids Res ; 50(W1): W670-W676, 2022 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-35544234

RESUMEN

RSAT (Regulatory Sequence Analysis Tools) enables the detection and the analysis of cis-regulatory elements in genomic sequences. This software suite performs (i) de novo motif discovery (including from genome-wide datasets like ChIP-seq/ATAC-seq) (ii) genomic sequences scanning with known motifs, (iii) motif analysis (quality assessment, comparisons and clustering), (iv) analysis of regulatory variations and (v) comparative genomics. RSAT comprises 50 tools. Six public Web servers (including a teaching server) are offered to meet the needs of different biological communities. RSAT philosophy and originality are: (i) a multi-modal access depending on the user needs, through web forms, command-line for local installation and programmatic web services, (ii) a support for virtually any genome (animals, bacteria, plants, totalizing over 10 000 genomes directly accessible). Since the 2018 NAR Web Software Issue, we have developed a large REST API, extended the support for additional genomes and external motif collections, enhanced some tools and Web forms, and developed a novel tool that builds or refine gene regulatory networks using motif scanning (network-interactions). The RSAT website provides extensive documentation, tutorials and published protocols. RSAT code is under open-source license and now hosted in GitHub. RSAT is available at http://www.rsat.eu/.


Asunto(s)
Genómica , Factores de Transcripción , Animales , Factores de Transcripción/genética , Genómica/métodos , Programas Informáticos , Análisis de Secuencia de ADN/métodos , Redes Reguladoras de Genes
5.
Respiration ; 102(10): 899-904, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37619549

RESUMEN

BACKGROUND: Ground-glass pulmonary nodules (GGNs) are most commonly sampled by percutaneous transthoracic biopsy. Diagnostic yield for ground-glass nodules using robotic-assisted bronchoscopy has been scarcely described, with a reported yield of 70.6%. OBJECTIVES: The aim of this study is to assess diagnostic yield for GGNs using shape-sensing robotic-assisted bronchoscopy (ssRAB). METHOD: A retrospective study of patients who underwent ssRAB for evaluation of GGNs, from September 2021 to April 2023. Primary outcome was diagnostic yield of ssRAB for GGNs, secondary outcomes were sensitivity for malignancy, and complications that required admission or intervention. RESULTS: A total of 23 nodules were biopsied from 22 patients. Median age was 71 years (IQR 66-81), 63.6% were female, and 40.9% had a previous history of cancer. Forty-three percent of nodules were in the right upper lobes, and the median lesion size was 1.8 × 1.21. Twelve were subsolid nodules (SSNs), and 11 were pure GGNs. Overall diagnostic yield was 87%, with a sensitivity for malignancy of 88.9%. Adenocarcinoma was the most common malignancy diagnosed (70%). No procedure-related complications were reported. CONCLUSION: The use of ssRAB shows a high diagnostic yield for diagnosing GGN and SSN with less than 6 mm solid component with a low risk for complications.


Asunto(s)
Neoplasias Pulmonares , Procedimientos Quirúrgicos Robotizados , Nódulo Pulmonar Solitario , Humanos , Femenino , Anciano , Masculino , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Broncoscopía , Tomografía Computarizada por Rayos X , Nódulo Pulmonar Solitario/diagnóstico por imagen , Nódulo Pulmonar Solitario/patología
6.
Int J Mol Sci ; 23(20)2022 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-36293279

RESUMEN

Vitamin D has an immune-modulating effect on respiratory tract infections. For this reason, it has been proposed as part of the treatment in COVID-19. Furthermore, vitamin D deficiency has been associated with worse clinical outcomes of this disease. The aim of this systematic review was to determine whether vitamin D supplementation modifies the disease course. Therefore, eleven studies involving randomised clinical trials are analysed, in which groups of COVID-19 patients with or without vitamin D supplementation as part of the treatment are compared. A control group was treated with best available therapy, and in some of the clinical trials, also with a placebo. According to the outcomes, it seems that patients benefit from receiving a daily or maintained in time vitamin D dose regardless of vitamin D serum levels at the beginning of the trial. The administration of a single vitamin D dose does not seem to have any effect on the health status of these patients. However, the outcomes are heterogeneous and larger clinical trials are necessary.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Deficiencia de Vitamina D , Humanos , Vitamina D/uso terapéutico , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológico , Vitaminas/uso terapéutico , Suplementos Dietéticos
7.
Neurogenetics ; 22(4): 343-346, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34296368

RESUMEN

Allan-Herndon-Dudley is an X-linked recessive syndrome caused by pathogenic variants in the SLC16A2 gene. Clinical manifestations are a consequence of impaired thyroid metabolism and aberrant transport of thyroid hormones to the brain. Carrier females are generally asymptomatic and may show subtle symptoms of the disease. We describe a female with a complete Allan-Herndon-Dudley phenotype, carrying a de novo 543-kb deletion of the X chromosome. The deletion encompasses exon 1 of the SLC16A2 gene and JPX and FTX genes; it is known that the latter two genes participate in the X-inactivation process upregulating XIST gene expression. Subsequent studies in the patient demonstrated the preferential expression of the X chromosome with the JPX and FTX deletion.


Asunto(s)
Discapacidad Intelectual Ligada al Cromosoma X/genética , Discapacidad Intelectual Ligada al Cromosoma X/patología , Hipotonía Muscular/genética , Hipotonía Muscular/patología , Atrofia Muscular/genética , Atrofia Muscular/patología , Mutación/genética , Inactivación del Cromosoma X/genética , Encéfalo/patología , Niño , Femenino , Humanos , Discapacidad Intelectual Ligada al Cromosoma X/diagnóstico , Transportadores de Ácidos Monocarboxílicos/genética , Hipotonía Muscular/diagnóstico , Atrofia Muscular/diagnóstico , Fenotipo , Simportadores/genética
8.
Brain ; 143(9): 2696-2708, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32875335

RESUMEN

Sarcoglycanopathies comprise four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. In 2016, several clinicians involved in the diagnosis, management and care of patients with LGMDR3-6 created a European Sarcoglycanopathy Consortium. The aim of the present study was to determine the clinical and genetic spectrum of a large cohort of patients with sarcoglycanopathy in Europe. This was an observational retrospective study. A total of 33 neuromuscular centres from 13 different European countries collected data of the genetically confirmed patients with sarcoglycanopathy followed-up at their centres. Demographic, genetic and clinical data were collected for this study. Data from 439 patients from 13 different countries were collected. Forty-three patients were not included in the analysis because of insufficient clinical information available. A total of 159 patients had a confirmed diagnosis of LGMDR3, 73 of LGMDR4, 157 of LGMDR5 and seven of LGMDR6. Patients with LGMDR3 had a later onset and slower progression of the disease. Cardiac involvement was most frequent in LGMDR4. Sixty per cent of LGMDR3 patients carried one of the following mutations, either in a homozygous or heterozygous state: c.229C>T, c.739G>A or c.850C>T. Similarly, the most common mutations in LMGDR5 patients were c.525delT or c.848G>A. In LGMDR4 patients the most frequent mutation was c.341C>T. We identified onset of symptoms before 10 years of age and residual protein expression lower than 30% as independent risk factors for losing ambulation before 18 years of age, in LGMDR3, LGMDR4 and LGMDR5 patients. This study reports clinical, genetic and protein data of a large European cohort of patients with sarcoglycanopathy. Improving our knowledge about these extremely rare autosomal recessive forms of LGMD was helped by a collaborative effort of neuromuscular centres across Europe. Our study provides important data on the genotype-phenotype correlation that is relevant for the design of natural history studies and upcoming interventional trials in sarcoglycanopathies.


Asunto(s)
Estudios de Asociación Genética , Sarcoglicanopatías/epidemiología , Sarcoglicanopatías/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios de Cohortes , Europa (Continente)/epidemiología , Femenino , Estudios de Asociación Genética/métodos , Humanos , Masculino , Persona de Mediana Edad , Distrofia Muscular de Cinturas/diagnóstico , Distrofia Muscular de Cinturas/epidemiología , Distrofia Muscular de Cinturas/genética , Estudios Retrospectivos , Sarcoglicanopatías/diagnóstico , Adulto Joven
9.
Nucleic Acids Res ; 47(10): 5016-5037, 2019 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-30923829

RESUMEN

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death.


Asunto(s)
Apoptosis , Diferenciación Celular , Cromatina/metabolismo , Histonas/metabolismo , Lisina/metabolismo , Células Mieloides/metabolismo , Acetilación , Animales , Células Cultivadas , Cromatina/genética , Epigénesis Genética , Humanos , Ratones Endogámicos C57BL , Ratones Noqueados , Células Mieloides/citología , Procesamiento Proteico-Postraduccional , Transcripción Genética
10.
Bioconjug Chem ; 29(2): 503-516, 2018 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-29357235

RESUMEN

The aim of this work was to prepare polypseudorotaxane-based supramolecular gels combining αCD with two temperature-responsive copolymers of different architecture (i.e., linear poloxamer P and X-shaped poloxamine T), at the lowest concentration as possible to form syringeable depots, and to shed light on the self-diffusion and spatial closeness of all components (including water) which in turn may determine the cooperative self-assembly phenomena and the performance of the gels at the macroscopic level. The exchange rate between bound water and bulk water was measured with a novel NMR experiment Water Diffusion Exchange-Diffusion Optimized Spectroscopy (WDE-DOSY). Polypseudorotaxane formation caused opposite effects on the mobility of αCD species (decreased) and internal water (increased) but did not affect PPO-water interaction. Consequently, designed ternary P/T/αCD supramolecular gels exhibited in situ gelling at body temperature could host large amounts of PLA/PLGA microspheres and behaved as porous 3D-scaffolds for mesenchymal stem cells (MSCs) supporting their osteogenic differentiation. Interestingly, the gels withstood freeze-drying and reconstitution with minor changes in inner structure and rheological properties. The gathered information may help to understand better the supramolecular gels and provide tools for the rational design of syringeable bone scaffolds that can simultaneously accommodate cells and drug microcarriers for efficient tissue regeneration.


Asunto(s)
Regeneración Ósea , Sustitutos de Huesos/química , Geles/química , Polímeros/química , Rotaxanos/química , Andamios del Tejido/química , Agua/química , Animales , Células Cultivadas , Difusión , Masculino , Células Madre Mesenquimatosas/citología , Osteogénesis , Ratas Sprague-Dawley , Reología
11.
Gynecol Oncol ; 150(3): 562-568, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30017537

RESUMEN

OBJECTIVE: Around 70% of uterine leiomyomas show MED12 mutations while overexpression of HMGA2 mRNA is also highly frequent in fibroids. However, previous studies suggested that alterations in both genes are mutually exclusive. In the present study, we searched for mutation in MED12 and analyzed the expression of HMGA2 in 20 uterine leiomyomas and their matched myometrium. METHODS: Normal and tumor tissue obtained from premenopausal women who underwent hysterectomy were collected after surgery and DNA, RNA and proteins were isolated and analyzed for MED12 mutations using Sanger sequencing, HMGA2 mRNA expression by quantitative PCR and HMGA2 protein detection by western blot and immunohistochemistry. RESULTS: 75% of the tumors displayed MED12 mutation while 65% of them showed overexpression of HMGA2 mRNA in leiomyomata compared to myometrial tissues (p = 0,0008). Interestingly, 50% of the tumors showed mutations in MED12 and overexpression of HMGA2 mRNA simultaneously, suggesting that alterations in both genes are relatively frequent in uterine leiomyomas. CONCLUSIONS: Contrary to the present findings, former studies showed that mutations in MED12 and overexpression of HMGA2 are mutually exclusive. Here, we observed that overexpression of HMGA2 mRNA in tumors measured by quantitative PCR and compared to myometrium is a common phenomenon in fibroids and is frequently associated with MED12 mutations. In addition, the common clonal origin of tumors overexpressing HMGA2 mRNA and its expression in few myometrial tissue points to HMGA2 up-regulation as an early event in leiomyoma tumorigenesis.


Asunto(s)
Proteína HMGA2/genética , Leiomioma/genética , Complejo Mediador/genética , ARN Mensajero/metabolismo , Neoplasias Uterinas/genética , Adulto , Femenino , Expresión Génica , Proteína HMGA2/metabolismo , Humanos , Leiomioma/metabolismo , Complejo Mediador/metabolismo , Persona de Mediana Edad , Mutación , Miometrio/metabolismo , Premenopausia , Neoplasias Uterinas/metabolismo
12.
Antonie Van Leeuwenhoek ; 110(4): 531-542, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28040856

RESUMEN

Bradyrhizobium diazoefficiens, a nitrogen-fixing endosymbiont of soybeans, is a model strain for studying rhizobial denitrification. This bacterium can also use nitrate as the sole nitrogen (N) source during aerobic growth by inducing an assimilatory nitrate reductase encoded by nasC located within the narK-bjgb-flp-nasC operon along with a nitrite reductase encoded by nirA at a different chromosomal locus. The global nitrogen two-component regulatory system NtrBC has been reported to coordinate the expression of key enzymes in nitrogen metabolism in several bacteria. In this study, we demonstrate that disruption of ntrC caused a growth defect in B. diazoefficiens cells in the presence of nitrate or nitrite as the sole N source and a decreased activity of the nitrate and nitrite reductase enzymes. Furthermore, the expression of narK-lacZ or nirA-lacZ transcriptional fusions was significantly reduced in the ntrC mutant after incubation under nitrate assimilation conditions. A B. diazoefficiens rpoN 1/2 mutant, lacking both copies of the gene encoding the alternative sigma factor σ54, was also defective in aerobic growth with nitrate as the N source as well as in nitrate and nitrite reductase expression. These results demonstrate that the NtrC regulator is required for expression of the B. diazoefficiens nasC and nirA genes and that the sigma factor RpoN is also involved in this regulation.


Asunto(s)
Proteínas Bacterianas/genética , Bradyrhizobium/metabolismo , Nitrato-Reductasa/metabolismo , Nitrito Reductasas/metabolismo , Factor sigma/genética , Proteínas Bacterianas/metabolismo , Bradyrhizobium/genética , Bradyrhizobium/crecimiento & desarrollo , Desnitrificación/fisiología , Nitrato-Reductasa/genética , Nitrito Reductasas/genética , Glycine max/microbiología
13.
Biochem J ; 473(3): 297-309, 2016 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-26564204

RESUMEN

Rhizobia are recognized to establish N2-fixing symbiotic interactions with legume plants. Bradyrhizobium japonicum, the symbiont of soybeans, can denitrify and grow under free-living conditions with nitrate (NO3 (-)) or nitrite (NO2 (-)) as sole nitrogen source. Unlike related bacteria that assimilate NO3 (-), genes encoding the assimilatory NO3 (-) reductase (nasC) and NO2 (-) reductase (nirA) in B. japonicum are located at distinct chromosomal loci. The nasC gene is located with genes encoding an ABC-type NO3 (-) transporter, a major facilitator family NO3 (-)/NO2 (-) transporter (NarK), flavoprotein (Flp) and single-domain haemoglobin (termed Bjgb). However, nirA clusters with genes for a NO3 (-)/NO2 (-)-responsive regulator (NasS-NasT). In the present study, we demonstrate NasC and NirA are both key for NO3 (-) assimilation and that growth with NO3 (-), but not NO2 (-) requires flp, implying Flp may function as electron donor to NasC. In addition, bjgb and flp encode a nitric oxide (NO) detoxification system that functions to mitigate cytotoxic NO formed as a by-product of NO3 (-) assimilation. Additional experiments reveal NasT is required for NO3 (-)-responsive expression of the narK-bjgb-flp-nasC transcriptional unit and the nirA gene and that NasS is also involved in the regulatory control of this novel bipartite assimilatory NO3 (-)/NO2 (-) reductase pathway.


Asunto(s)
Bradyrhizobium/metabolismo , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Bradyrhizobium/enzimología , Bradyrhizobium/genética , Regulación Bacteriana de la Expresión Génica , Proteínas de Transporte de Membrana/metabolismo , Nitrito Reductasas/genética , Nitrito Reductasas/metabolismo , Nitritos/metabolismo
14.
Breast Cancer Res ; 18(1): 29, 2016 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-26956474

RESUMEN

BACKGROUND: Somatostatin (SST) and cortistatin (CORT), two structurally and functionally related peptides, share a family of widespread receptors (sst1-5) to exert apparently similar biological actions, including endocrine/metabolic regulation and suppression of tumor cell proliferation. However, despite their therapeutic potential, attempts to apply SST-analogs to treat breast cancer have yielded unsatisfactory results. Actually, the specific roles of SST and CORT in mammary gland tumorigenesis (MGT), particularly in relation to metabolic dysregulation (i.e. obesity), remain unknown. METHODS: The role of endogenous SST and CORT in carcinogen-induced MGT was investigated under normal (lean) and obesity conditions. To that end, SST- and CORT-knockout (KO) mice and their respective littermate-controls, fed low-fat (LF) or high-fat (HF) diets, were treated with 7,12-dimethyl-benza-anthracene (DMBA) once a week (wk) for 3 wk, and MGT was monitored for 25 wk. Additionally, we examined the effect of SST or CORT removal in the development of the mammary gland. RESULTS: Lack of SST did not alter DMBA-induced MGT incidence under lean conditions; conversely, lack of endogenous CORT severely aggravated DMBA-induced MGT in LF-fed mice. These differences were not attributable to altered mammary gland development. HF-diet modestly increased the sensitivity to DMBA-induced carcinogenesis in control mice, whereas, as observed in LF-fed CORT-KO, HF-fed CORT-KO mice exhibited aggravated tumor incidence, discarding a major influence of obesity on these CORT actions. In marked contrast, HF-fed SST-KO mice exhibited much higher tumor incidence than LF-fed SST-KO mice, which could be associated with higher mammary complexity. CONCLUSIONS: Endogenous SST and CORT distinctly impact on DMBA-induced MGT, in a manner that is strongly dependent on the metabolic/endocrine milieu (lean vs. obese status). Importantly, CORT, rather than SST, could represent a major inhibitor of MGT under normal/lean-conditions, whereas both neuropeptides would similarly influence MGT under obesity conditions. The mechanisms mediating these different effects likely involve mammary development and hormones, but the precise underlying factors are still to be fully elucidated. However, our findings comprise suggestive evidence that CORT-like molecules, rather than classic SST-analogs, may help to identify novel tools for the medical treatment of breast cancer.


Asunto(s)
Carcinogénesis/genética , Neoplasias Mamarias Animales/genética , Neuropéptidos/genética , Somatostatina/genética , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Animales , Femenino , Humanos , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/patología , Neoplasias Mamarias Animales/inducido químicamente , Neoplasias Mamarias Animales/patología , Ratones , Ratones Noqueados , Ratones Obesos/genética
15.
Folia Parasitol (Praha) ; 622015 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-25960548

RESUMEN

Lepeophtheirus simplex Ho, Gómez et Fajer-Avila, 2001 is a parasite of Sphoeroides annulatus (Jenyns), an economically important fish species, with potential for aquaculture, in northwestern Mexico. The goal of this study was to describe the developmental stages under experimental conditions and seasonal fecundity of this parasite on wild fish. There are two naupliar, one copepodid, two chalimus and two pre-adult stages preceding the adult of L. simplex. The results support previous findings, which point out that the life cycle of the caligid copepods includes only six post-naupliar stages. The generation time from egg extrusion to adult for L. simplex was approximately 10 days at 22 °C. The body length of the ovigerous females ranged between 2.2 and 4.1 mm, and its fecundity between 12 and 36 eggs per string. Fecundity was negatively correlated with the egg size and positively correlated with the egg string length. Our data did not reveal significant differences in fecundity among sampling months, but ovigerous females were significantly larger in March (when water temperature was 22 °C) than in June and July (when water temperature was 30 °C). To some extent, our fecundity results contrast with those found in species of sea lice from higher latitudes. Undoubtedly, biological information on different species of sea lice from different environmental conditions will enhance our understanding of their infection strategies and will be valuable, given the increasing interest in marine fish farming in Mexico.

16.
Rev Invest Clin ; 67(2): 89-97, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25938841

RESUMEN

BACKGROUND: Delayed graft function (DGF) is defined as the need for dialysis within the first seven days of transplantation. The frequency of DGF has decreased in the last five years compared with the previous 20 years of the kidney transplant program at a Mexican referral hospital. OBJECTIVE: To determine the incidence and risk factors for DGF in the past five years (2009-2013). METHODS: We analyzed a retrospective cohort of renal transplant recipients from deceased donors at our hospital between March 2009 and May 2013 (Period 2), and compared the results with a previously evaluated cohort (Period 1, between January 1990 and February 2009). RESULTS: During the analyzed period, 78 deceased donor transplants were performed. The frequency of DGF was 9%. Multivariate analysis showed that recipient older age (OR: 1.074419; 95% CI: 1.0009-1.155116; p = 0.05), transoperative amines administration (OR: 7.73; 95% CI: 1.037-57.6; p = 0.046), and hypotension during surgery in the recipient (OR: 11.6; 95% CI: 1.33-100.8; p = 0.026) were risk factors for DGF. CONCLUSION: The incidence of DGF has significantly decreased in the past five years when compared to the previous 20 years in our hospital.


Asunto(s)
Aminas/administración & dosificación , Funcionamiento Retardado del Injerto/epidemiología , Hipotensión/epidemiología , Trasplante de Riñón , Adulto , Factores de Edad , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , México , Persona de Mediana Edad , Análisis Multivariante , Diálisis Renal , Estudios Retrospectivos , Factores de Riesgo , Centros de Atención Terciaria
17.
Parasitol Res ; 113(1): 139-47, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24158646

RESUMEN

For a deeper understanding of the phylogenetic relationships of Echinococcus genotypes and species in different intermediate hosts, we analyzed samples from human and bovine hydatid cysts. For this, segments of the cytochrome oxidase (COX1) and NADH dehydrogenase (ND1) mitochondrial genes were used. To obtain sufficient amounts of the ND1 marker to be sequenced properly, a new variant of the PCR assay was implemented. Phylogenetic analysis with both markers showed that most of the analyzed samples correspond to genotype G1. However, a sample from cysts of a bovine lung (Q21), with the COX1 marker, was grouped in a node together with a sample belonging to genotype G3. In the phylogenetic tree obtained with the ND1 marker, this sample was grouped with sequences of genotypes G3, G2, and G4. Analyzing the single nucleotide polymorphic (SNP) sites of both markers, it was observed that the Q21 sequence is almost identical to the G3 sequence and differ in only one SNP from the G2 sequence, and is completely different from G4. These results are noteworthy, since neither G2 nor G3 genotypes have been described previously in Chile, raising the possibility that the G3 genotype is present in these latitudes. This information is highly relevant; it can be employed to uncover additional unknown details of transmission cycles of this important parasite.


Asunto(s)
Bovinos/parasitología , Equinococosis/veterinaria , Echinococcus granulosus/clasificación , Genotipo , Animales , Chile , ADN de Helmintos/genética , Equinococosis/parasitología , Echinococcus granulosus/genética , Complejo IV de Transporte de Electrones/genética , Genes Mitocondriales , Marcadores Genéticos , NADH Deshidrogenasa/genética , Filogenia , Reacción en Cadena de la Polimerasa/veterinaria , Polimorfismo de Nucleótido Simple
18.
Pharm Biol ; 52(7): 835-40, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24920228

RESUMEN

CONTEXT: Traditionally, the content of total phenolics (flavonoid phenolics (FP) and non-flavonoid phenolics (NFP)) and flavonoids (flavone/flavonol and flavonone/dihydroflavonol) in propolis has been determined by different methodologies. Until now, the percentage of total phenolic (TP) compounds that corresponds to FP and NFP, expressed in the same units by a spectrophotometric method, has not been determined. OBJECTIVE: The current study proposes a quick and simple methodology that separates FP and NFP in propolis samples and determines TP, FP, and NFP by the same method. MATERIALS AND METHODS: Propolis samples from five Argentine provinces (Tucumán, Santiago del Estero, Salta, Misiones, and Jujuy) were used. Extraction of TP from the propolis samples was carried out by maceration with 80% ethanol and quantified by Folin-Ciocalteu reagent (FC-R). Then, FP was precipitated with formaldehyde in acid medium. After centrifugation, NFP were determined in the supernatant using FC-R. FP content was calculated as the difference between the content of TP and NFP. The method was also validated using commercial flavonoids and chalcones. RESULTS: FP recovery in all experiments was between 85.95% and 98.29%. Propolis from Tucumán had significantly higher amounts of total phenols than propolis from other provinces. SE5 showed higher content of FP (81.52%) followed by SA1 (74.75%). The propolis from TUC4, SA4, SE3, and MI showed the lowest FP content and highest content of NFP. CONCLUSIONS: This method provides a simple, reliable, and specific spectrophotometric assay to estimate the content of NFP, FP, and TP in propolis samples.


Asunto(s)
Flavonoides/análisis , Fenoles/análisis , Própolis/química , Cromatografía en Capa Delgada , Flavonoides/aislamiento & purificación , Indicadores y Reactivos/química , Molibdeno/química , Fenoles/aislamiento & purificación , Espectrofotometría , Compuestos de Tungsteno/química
19.
Cancer Epidemiol Biomarkers Prev ; 33(6): 838-845, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38578081

RESUMEN

BACKGROUND: The American Indian (AI) population in North Carolina has limited access to the Indian Health Service. Consequently, cancer burden and disparities may differ from national estimates. We describe the AI cancer population and examine AI-White disparities in cancer incidence and mortality. METHODS: We identified cancer cases diagnosed among adult AI and White populations between 2014 and 2018 from the North Carolina Central Cancer Registry. We estimated incidence and mortality rate ratios (IRR and MRR) by race. In addition, between the AI and White populations, we estimated the ratio of relative frequency differences [RRF, with 95% confidence limits (CL)] of clinical and sociodemographic characteristics. Finally, we evaluated the geographic distribution of incident diagnoses among AI populations. RESULTS: Our analytic sample included 2,161 AI and 204,613 White individuals with cancer. Compared with the White population, the AI population was more likely to live in rural areas (48% vs. 25%; RRF, 1.89; 95% CL, 1.81-1.97) and to have Medicaid (18% vs. 7%; RRF, 2.49; 95% CL, 2.27-2.71). Among the AI population, the highest age-standardized incidence rates were female breast, followed by prostate and lung and bronchus. Liver cancer incidence was significantly higher among the AI population than White population (IRR, 1.27; 95% CL, 1.01-1.59). AI patients had higher mortality rates for prostate (MRR, 1.72; CL, 1.09-2.70), stomach (MRR, 1.82; 95% CL, 1.15-2.86), and liver (MRR, 1.70; 95% CL, 1.25-2.33) cancers compared with White patients. CONCLUSIONS: To reduce prostate, stomach, and liver cancer disparities among AI populations in North Carolina, multi-modal interventions targeting risk factors and increasing screening and treatment are needed. IMPACT: This study identifies cancer disparities that can inform targeted interventions to improve outcomes among AI populations in North Carolina.


Asunto(s)
Neoplasias , Humanos , Masculino , Neoplasias/epidemiología , Neoplasias/etnología , Neoplasias/mortalidad , North Carolina/epidemiología , Femenino , Persona de Mediana Edad , Anciano , Incidencia , Adulto , Sistema de Registros/estadística & datos numéricos , Indio Americano o Nativo de Alaska/estadística & datos numéricos , Adulto Joven , Población Blanca/estadística & datos numéricos
20.
Cureus ; 16(4): e57414, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38694634

RESUMEN

Purpose The increasing use of computed tomography (CT) imaging has led to the detection of more ground-glass nodules (GGNs) and subsolid nodules (SSNs), which may be malignant and require a biopsy for proper diagnosis. Approximately 75% of persistent GGNs can be attributed to adenocarcinoma in situ or minimally invasive adenocarcinoma. A CT-guided biopsy has been proven to be a reliable procedure with high diagnostic performance. However, the diagnostic accuracy and safety of a CT-guided biopsy for GGNs and SSNs with solid components ≤6 mm are still uncertain. The aim of this study is to assess the diagnostic accuracy of a CT-guided core needle biopsy (CNB) for GGN and SSNs with solid components ≤6 mm. Methods This is a retrospective study of patients who underwent CT-guided CNB for the evaluation of GGNs and SSNs with solid components ≤6 mm between February 2020 and January 2023. Biopsy findings were compared to the final diagnosis determined by definite histopathologic examination and clinical course. Results A total of 22 patients were enrolled, with a median age of 74 years (IQR: 68-81). A total of 22 nodules were assessed, comprising 15 (68.2%) SSNs with a solid component measuring ≤6 mm and seven (31.8%) pure GGNs. The histopathological examination revealed that 12 (54.5%) were diagnosed as malignant, nine (40.9%) as benign, and one (4.5%) as non-diagnostic. The overall diagnostic accuracy and sensitivity for malignancy were 86.36% and 85.7%, respectively. Conclusion A CT-guided CNB for GGNs and SSNs with solid components measuring ≤6 mm appears to have a high diagnostic accuracy.

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