Recent Advances in Tomato Gene Editing.

The use of gene-editing tools, such as zinc finger nucleases, TALEN, and CRISPR/Cas, allows for the modification of physiological, morphological, and other characteristics in a wide range of crops to mitigate the negative effects of stress caused by anthropogenic climate change or biotic stresses. Importantly, these tools have the potential to improve crop resilience and increase yields in response to challenging environmental conditions. This review provides an overview of gene-editing techniques used in plants, focusing on the cultivated tomatoes. Several dozen genes that have been successfully edited with the CRISPR/Cas system were selected for inclusion to illustrate the possibilities of this technology in improving fruit yield and quality, tolerance to pathogens, or responses to drought and soil salinity, among other factors. Examples are also given of how the domestication of wild species can be accelerated using CRISPR/Cas to generate new crops that are better adapted to the new climatic situation or suited to use in indoor agriculture.

Genes involved in auxin biosynthesis, transport and signalling underlie the extreme adventitious root phenotype of the tomato aer mutant.

The use of tomato rootstocks has helped to alleviate the soaring abiotic stresses provoked by the adverse effects of climate change. Lateral and adventitious roots can improve topsoil exploration and nutrient uptake, shoot biomass and resulting overall yield. It is essential to understand the genetic basis of root structure development and how lateral and adventitious roots are produced. Existing mutant lines with specific root phenotypes are an excellent resource to analyse and comprehend the molecular basis of root developmental traits. The tomato aerial roots (aer) mutant exhibits an extreme adventitious rooting phenotype on the primary stem. It is known that this phenotype is associated with restricted polar auxin transport from the juvenile to the more mature stem, but prior to this study, the genetic loci responsible for the aer phenotype were unknown. We used genomic approaches to define the polygenic nature of the aer phenotype and provide evidence that increased expression of specific auxin biosynthesis, transport and signalling genes in different loci causes the initiation of adventitious root primordia in tomato stems. Our results allow the selection of different levels of adventitious rooting using molecular markers, potentially contributing to rootstock breeding strategies in grafted vegetable crops, especially in tomato. In crops vegetatively propagated as cuttings, such as fruit trees and cane fruits, orthologous genes may be useful for the selection of cultivars more amenable to propagation.

Temporal profiling of physiological, histological, and transcriptomic dissection during auxin-induced adventitious root formation in tetraploid Robinia pseudoacacia micro-cuttings.

MAIN CONCLUSION: Optimal levels of indole-3-butyric acid (IBA) applied at the stem base promote adventitious root (AR) initiation and primordia formation, thus promoting the rooting of leafy micro-cuttings of tetraploid Robinia pseudoacacia. Tetraploid Robinia pseudoacacia L. is a widely cultivated tree in most regions of China that has a hard-rooting capability, propagated by stem cuttings. This study utilizes histological, physiological, and transcriptomic approaches to explore how root primordia are induced after indole butyric acid (IBA) treatment of micro-cuttings. IBA application promoted cell divisions in some cells within the vasculature, showing subcellular features associated with adventitious root (AR) founder cells. The anatomical structure explicitly showed that AR initiated from the cambium layer and instigate the inducible development of AR primordia. Meanwhile, the hormone data showed that similar to that of indole-3-acetic acid, the contents of trans-zeatin and abscisic acid peaked at early stages of AR formation and increased gradually in primordia formation across the subsequent stages, suggesting their indispensable roles in AR induction. On the contrary, 24-epibrassinolide roughly maintained at extremely high levels during primordium initiation thoroughly, indicating its presence was involved in cell-specific reorganization during AR development. Furthermore, antioxidant activities transiently increased in the basal region of micro-cuttings and may serve as biochemical indicators for distinct rooting phases, potentially aiding in AR formation. Transcriptomic analysis during the early stages of root formation shows significant downregulation of the abscisic acid and jasmonate signaling pathways, while ethylene and cytokinin signaling seems upregulated. Network analysis of genes involved in carbon metabolism and photosynthesis indicates that the basal region of the micro-cuttings undergoes rapid reprogramming, which results in the breakdown of sugars into pyruvate. This pyruvate is then utilized to fuel the tricarboxylic acid cycle, thereby sustaining growth through aerobic respiration. Collectively, our findings provide a time-course morphophysiological dissection and also suggest the regulatory role of a conserved auxin module in AR development in these species.

Regulation of early seedling establishment and root development in Arabidopsis thaliana by light and carbohydrates.

MAIN CONCLUSION: Root development is regulated by sucrose and light during early seedling establishment through changes in the auxin response and chromatin topology. Light is a key environmental signal that regulates plant growth and development. The impact of light on development is primarily analyzed in the above-ground tissues, but little is known about the mechanisms by which light shapes the architecture of underground roots. Our study shows that carbohydrate starvation during skotomorphogenesis is accompanied by compaction of nuclei in the root apical meristem, which prevents cell cycle progression and leads to irreversible root differentiation in the absence of external carbohydrates, as evidenced by the lack of DNA replication and increased numbers of nuclei with specific chromatin characteristics. In these conditions, induction of photomorphogenesis was unable to restore seedling growth, as overall root growth was compromised. The addition of carbohydrates, either locally or systemically by transferring seedlings to sugar-containing medium, led to the induction of adventitious root formation with rapid recovery of seedling growth. Conversely, transferring in vitro carbohydrate-grown seedlings from light to dark transiently promoted cell elongation and significantly reduced root meristem size, but did not primarily affect cell cycle kinetics. We show that, in the presence of sucrose, dark incubation does not affect zonation in the root apical meristem but leads to shortening of the proliferative and transition zones. Sugar starvation led to a rapid increase in lysine demethylation of histone H3 at position K9, which preceded a rapid decline in cell cycle activity and activation of cell differentiation. In conclusion, carbohydrates are required for cell cycle activity, epigenetics reprogramming and for postmitotic cell elongation and auxin-regulated response in the root apical meristem.

The Role of Gender Differences and Menopause in Obesity-Related Renal Disease, Renal Inflammation and Lipotoxicity.

The pathogenesis of obesity-related-renal disease is unknown. Menopause can promote renal disease in obese women, but this interaction is unclear. In a previous study, we observed that obese male and female mice developed albuminuria, hyperfiltration, and glomerulomegaly, and these changes were more severe in those obese ovariectomized females. In this study, we also evaluated renal inflammation and lipotoxicity in that animal model. For six months, 43 males and 36 females C57BL6/J mice were randomized to standard diet (SD) or high fat diet (HFD). A group of female animals on SD or HFD was ovariectomized to simulate menopause. We evaluated cytokines: NF-κß p65, IL-1ß, MCP-1, TNF-α, total lipid content, lipid classes, and fatty acid profile in total lipid and individual lipid classes in renal tissue and urine. We found that obese males and females showed higher NF-kß p-65, TNF-α and MCP-1 in renal tissue, and obese females ovariectomized had higher IL-1ß and TNF-α compared with not-ovariectomized. Also, obese animals showed lower proinflammatory and higher anti-inflammatory fatty acids in kidney total lipids, while obese females ovariectomized had a more exacerbated pattern. In brief, obesity induces inflammation and an unbalanced lipidic profile in renal tissue. This pattern seems to be enhanced in obesity after menopause.

Optimization of Callus Induction and Shoot Regeneration from Tomato Cotyledon Explants.

Cultivated tomato (Solanum lycopersicum L.) is one of the most important horticultural crops in the world. The optimization of culture media for callus formation and tissue regeneration of different tomato genotypes presents numerous biotechnological applications. In this work, we have analyzed the effect of different concentrations of zeatin and indole-3-acetic acid on the regeneration of cotyledon explants in tomato cultivars M82 and Micro-Tom. We evaluated regeneration parameters such as the percentage of callus formation and the area of callus formed, as well as the initiation percentage and the number of adventitious shoots. The best hormone combination produced shoot-like structures after 2-3 weeks. We observed the formation of leaf primordia from these structures after about 3-4 weeks. Upon transferring the regenerating micro-stems to a defined growth medium, it was possible to obtain whole plantlets between 4 and 6 weeks. This hormone combination was applied to other genotypes of S. lycopersicum, including commercial varieties and ancestral tomato varieties. Our method is suitable for obtaining many plantlets of different tomato genotypes from cotyledon explants in a very short time, with direct applications for plant transformation, use of gene editing techniques, and vegetative propagation of elite cultivars.

Coexistence of persistent fetal vasculature and retinoblastoma in the same eye.

BACKGROUND: As retinoblastoma (RB) is the most frequent primary intraocular malignant tumor in childhood, it should be the main pathology to rule out in pediatric patients with leukocoria. Persistence of fetal vasculature (PFV) is within the differential diagnosis of leukocoria, a vitreous disorder arising from a defect in the involution of the hyaloid vasculature in the embryonic stage, which affects normal ocular development and commonly produces associated microophthalmia. An early diagnosis and timely treatment are crucial for a better prognosis and life expectancy of the child. CASE REPORT: We present a case of retinoblastoma and coexisting with PFV: a 2-years-and 11-months-old male with no red reflex, and vasculature and yellowish-white membrane behind the lens of the right eye. B-mode ultrasound with disorganization of the vitreous cavity with high reflectivity echoes suggestive of calcification. On examination we found an enlarged eyeball, rubeosis iridis, posterior vasculature, intraocular pressure 28 mmHg. Computed tomography with heterogeneous intraocular mass with hyperdense regions. With a diagnosis of probable retinoblastoma, enucleation was performed. Histopathology reported moderately differentiated retinoblastoma coexisting with PFV. CONCLUSIONS: The finding of these two diagnoses in the same eye is very rare due to the different pathophysiology.

INTRODUCCIÓN: El retinoblastoma (RB) es el tumor maligno primario intraocular más frecuente en la infancia y debe ser la principal patología a descartar en los pacientes pediátricos con leucocoria. La persistencia de la vasculatura fetal (PVF) está dentro del diagnóstico diferencial de la leucocoria, un trastorno del vítreo que surge de un defecto en la involución de la vasculatura hialoidea en la etapa embrionaria que afecta al desarrollo ocular normal y comúnmente produce microoftalmia asociada. El diagnóstico temprano y tratamiento oportuno son cruciales para un buen pronóstico y mejor esperanza de vida del infante. CASO CLÍNICO: Presentamos un caso de coexistencia de retinoblastoma y PVF: paciente de sexo masculino de 2 años y 11 meses sin reflejo rojo y vasculatura y membrana blanco-amarillenta detrás del cristalino en el ojo derecho. La ecografía en modo B con desorganización de la cavidad vítrea con ecos de alta reflectividad sugestivos de calcificación. A la exploración se observó globo ocular agrandado, rubeosis iridis, vasculatura posterior, presión intraocular 28 mmHg. Tomografía computarizada con masa intraocular heterogénea con regiones hiperdensas. Con diagnóstico de probable retinoblastoma, se realizó la enucleación. La histopatología informó el hallazgo de retinoblastoma moderadamente diferenciado coexistente con PVF. CONCLUSIONES: El hallazgo de estos dos diagnósticos en un mismo ojo es muy poco frecuente debido a la diferente fisiopatología.

Epileptic spasms in CDKL5 deficiency disorder: Delayed treatment and poor response to first-line therapies.

OBJECTIVE: We aimed to assess the treatment response of infantile-onset epileptic spasms (ES) in CDKL5 deficiency disorder (CDD) vs other etiologies. METHODS: We evaluated patients with ES from the CDKL5 Centers of Excellence and the National Infantile Spasms Consortium (NISC), with onset from 2 months to 2 years, treated with adrenocorticotropic hormone (ACTH), oral corticosteroids, vigabatrin, and/or the ketogenic diet. We excluded children with tuberous sclerosis complex, trisomy 21, or unknown etiology with normal development because of known differential treatment responses. We compared the two cohorts for time to treatment and ES remission at 14 days and 3 months. RESULTS: We evaluated 59 individuals with CDD (79% female, median ES onset 6 months) and 232 individuals from the NISC database (46% female, median onset 7 months). In the CDD cohort, seizures prior to ES were common (88%), and hypsarrhythmia and its variants were present at ES onset in 34%. Initial treatment with ACTH, oral corticosteroids, or vigabatrin started within 1 month of ES onset in 27 of 59 (46%) of the CDD cohort and 182 of 232 (78%) of the NISC cohort (p < .0001). Fourteen-day clinical remission of ES was lower for the CDD group (26%, 7/27) than for the NISC cohort (58%, 106/182, p = .0002). Sustained ES remission at 3 months occurred in 1 of 27 (4%) of CDD patients vs 96 of 182 (53%) of the NISC cohort (p < .0001). Comparable results were observed with longer lead time (≥1 month) or prior treatment. Ketogenic diet, used within 3 months of ES onset, resulted in ES remission at 1 month, sustained at 3 months, in at least 2 of 13 (15%) individuals with CDD. SIGNIFICANCE: Compared to the broad group of infants with ES, children with ES in the setting of CDD often experience longer lead time to treatment and respond poorly to standard treatments. Development of alternative treatments for ES in CDD is needed.

Analysis of the cytotoxic and genotoxic effects in a population chronically exposed to coal mining residues.

During coal mining activities, many compounds are released into the environment that can negatively impact human health. Particulate matter, polycyclic aromatic hydrocarbons (PAHs), metals, and oxides are part of the complex mixture that can affect nearby populations. Therefore, we designed this study to evaluate the potential cytotoxic and genotoxic effects in individuals chronically exposed to coal residues from peripheral blood lymphocytes and buccal cells. We recruited 150 individuals who lived more than 20 years in La Loma-Colombia and 120 control individuals from the city of Barranquilla without a history of exposure to coal mining. In the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay, significant differences in the frequency of micronucleus (MN), nucleoplasmic bridge (NPB), nuclear bud (NBUD), and apoptotic cells (APOP) were observed between the two groups. In the buccal micronucleus cytome (BM-Cyt) assay, a significant formation of NBUD, karyorrhexis (KRX), karyolysis (KRL), condensed chromatin (CC), and binucleated (BN) cells was observed in the exposed group. Considering the characteristics of the study group, a significant correlation for CBMN-Cyt was found between NBUD and vitamin consumption, between MN or APOP and meat consumption, and between MN and age. Moreover, a significant correlation for BM-Cyt was found between KRL and vitamin consumption or age, and BN versus alcohol consumption. Using Raman spectroscopy, a significant increase in the concentration of DNA/RNA bases, creatinine, polysaccharides, and fatty acids was detected in the urine of individuals exposed to coal mining compared to the control group. These results contribute to the discussion on the effects of coal mining on nearby populations and the development of diseases due to chronic exposure to these residues.

Role of reactive oxygen species in the modulation of auxin flux and root development in Arabidopsis thaliana.

Reactive oxygen species (ROS) play a dual role in plant biology, acting as important signal transduction molecules and as toxic byproducts of aerobic metabolism that accumulate in cells upon exposure to different stressors and lead to cell death. In plants, root architecture is regulated by the distribution and intercellular flow of the phytohormone auxin. In this study, we identified ROS as an important modulator of auxin distribution and response in the root. ROS production is necessary for root growth, proper tissue patterning, cell growth, and lateral root (LR) induction. Alterations in ROS balance led to altered auxin distribution and response in SOD and RHD2 loss-of-function mutants. Treatment of Arabidopsis seedlings with additional sources of ROS (hydrogen peroxide) or an ROS production inhibitor (diphenylene iodonium) induced phenocopies of the mutants studied. Simultaneous application of auxin and ROS increased LR primordia induction, and PIN-FORMED protein immunolocalization further demonstrated the existing link between auxin and ROS in orchestrating cell division and auxin flux during root development. In Arabidopsis roots, genetic alterations in ROS balance led to defective auxin distribution and growth-related responses in roots. Exogenous hydrogen peroxide alters the establishment of the endogenous auxin gradient in the root meristem through regulation of PIN-FORMED polarity, while the simultaneous application of hydrogen peroxide and auxin enhanced LR induction in a dose- and position-dependent manner through activation of cell division.

Mapping of the Classical Mutation rosette Highlights a Role for Calcium in Wound-Induced Rooting.

Removal of the root system induces the formation of new roots from the remaining shoot. This process is primarily controlled by the phytohormone auxin, which interacts with other signals in a yet unresolved manner. Here, we study the classical tomato mutation rosette (ro), which lacks shoot-borne roots. ro mutants were severely inhibited in formation of wound-induced roots (WiRs) and had reduced auxin transport rates. We mapped ro to the tomato ortholog of the Arabidopsis thaliana BIG and the mammalians UBR4/p600. RO/BIG is a large protein of unknown biochemical function. In A. thaliana, BIG was implicated in regulating auxin transport and calcium homeostasis. We show that exogenous calcium inhibits WiR formation in tomato and A. thaliana ro/big mutants. Exogenous calcium antagonized the root-promoting effects of the auxin indole-3-acetic-acid but not of 2,4-dichlorophenoxyacetic acid, an auxin analog that is not recognized by the polar transport machinery, and accumulation of the auxin transporter PIN-FORMED1 (PIN1) was sensitive to calcium levels in the ro/big mutants. Consistent with a role for calcium in mediating auxin transport, both ro/big mutants and calcium-treated wild-type plants were hypersensitive to treatment with polar auxin transport inhibitors. Subcellular localization of BIG suggests that, like its mammalian ortholog, it is associated with the endoplasmic reticulum. Analysis of subcellular morphology revealed that ro/big mutants exhibited disruption in cytoplasmic streaming. We suggest that RO/BIG maintains auxin flow by stabilizing PIN membrane localization, possibly by attenuating the inhibitory effect of Ca2+ on cytoplasmic streaming.

Transcriptomic and hormonal analysis of the roots of maize seedlings grown hydroponically at low temperature.

Prolonged cold stress has a strong effect on plant growth and development, especially in subtropical crops such as maize. Soil temperature limits primary root elongation, mainly during early seedling establishment. However, little is known about how moderate temperature fluctuations affect root growth at the molecular and physiological levels. We have studied root tips of young maize seedlings grown hydroponically at 30 ºC and after a short period (up to 24 h) of moderate cooling (20 ºC). We found that both cell division and cell elongation in the root apical meristem are affected by temperature. Time-course analyses of hormonal and transcriptomic profiles were achieved after temperature reduction from 30 ºC to 20 ºC. Our results highlighted a complex regulation of endogenous pathways leading to adaptive root responses to moderate cooling conditions.

The upper-airway microbiome as a biomarker of asthma exacerbations despite inhaled corticosteroid treatment.

BACKGROUND: The response to inhaled corticosteroids (ICS) in asthma is affected by the interplay of several factors. Among these, the role of the upper-airway microbiome has been scarcely investigated. We aimed to evaluate the association between the salivary, pharyngeal, and nasal microbiome with asthma exacerbations despite receipt of ICS. METHODS: Samples from 250 asthma patients from the Genomics and Metagenomics of Asthma Severity (GEMAS) study treated with ICS were analyzed. Control/case subjects were defined by the absence/presence of asthma exacerbations in the past 6 months despite being treated with ICS. The bacterial microbiota was profiled by sequencing the V3-V4 region of the 16S rRNA gene. Differences between groups were assessed by PERMANOVA and regression models adjusted for potential confounders. A false discovery rate (FDR) of 5% was used to correct for multiple comparisons. Classification models of asthma exacerbations despite ICS treatment were built with machine learning approaches based on clinical, genetic, and microbiome data. RESULTS: In nasal and saliva samples, case subjects had lower bacterial diversity (Richness, Shannon, and Faith indices) than control subjects (.007 ≤ P ≤ .037). Asthma exacerbations accounted for 8% to 9% of the interindividual variation of the salivary and nasal microbiomes (.003 ≤ P ≤ .046). Three, 4, and 11 bacterial genera from the salivary, pharyngeal, and nasal microbiomes were differentially abundant between groups (4.09 × 10-12 ≤ FDR ≤ 0.047). Integrating clinical, genetic, and microbiome data showed good discrimination for the development of asthma exacerbations despite receipt of ICS (AUCtraining: 0.82 and AUCvalidation: 0.77). CONCLUSION: The diversity and composition of the upper-airway microbiome are associated with asthma exacerbations despite ICS treatment. The salivary microbiome has a potential application as a biomarker of asthma exacerbations despite receipt of ICS.

Coexistencia de vasculatura fetal persistente y retinoblastoma en el mismo ojo / Coexistence of persistent fetal vasculature and retinoblastoma in the same eye

Resumen Introducción: El retinoblastoma (RB) es el tumor maligno primario intraocular más frecuente en la infancia y debe ser la principal patología a descartar en los pacientes pediátricos con leucocoria. La persistencia de la vasculatura fetal (PVF) está dentro del diagnóstico diferencial de la leucocoria, un trastorno del vítreo que surge de un defecto en la involución de la vasculatura hialoidea en la etapa embrionaria que afecta al desarrollo ocular normal y comúnmente produce microoftalmia asociada. El diagnóstico temprano y tratamiento oportuno son cruciales para un buen pronóstico y mejor esperanza de vida del infante. Caso clínico: Presentamos un caso de coexistencia de retinoblastoma y PVF: paciente de sexo masculino de 2 años y 11 meses sin reflejo rojo y vasculatura y membrana blanco-amarillenta detrás del cristalino en el ojo derecho. La ecografía en modo B con desorganización de la cavidad vítrea con ecos de alta reflectividad sugestivos de calcificación. A la exploración se observó globo ocular agrandado, rubeosis iridis, vasculatura posterior, presión intraocular 28 mmHg. Tomografía computarizada con masa intraocular heterogénea con regiones hiperdensas. Con diagnóstico de probable retinoblastoma, se realizó la enucleación. La histopatología informó el hallazgo de retinoblastoma moderadamente diferenciado coexistente con PVF. Conclusiones: El hallazgo de estos dos diagnósticos en un mismo ojo es muy poco frecuente debido a la diferente fisiopatología.

Abstract Background: As retinoblastoma (RB) is the most frequent primary intraocular malignant tumor in childhood, it should be the main pathology to rule out in pediatric patients with leukocoria. Persistence of fetal vasculature (PFV) is within the differential diagnosis of leukocoria, a vitreous disorder arising from a defect in the involution of the hyaloid vasculature in the embryonic stage, which affects normal ocular development and commonly produces associated microophthalmia. An early diagnosis and timely treatment are crucial for a better prognosis and life expectancy of the child. Case report: We present a case of retinoblastoma and coexisting with PFV: a 2-years-and 11-months-old male with no red reflex, and vasculature and yellowish-white membrane behind the lens of the right eye. B-mode ultrasound with disorganization of the vitreous cavity with high reflectivity echoes suggestive of calcification. On examination we found an enlarged eyeball, rubeosis iridis, posterior vasculature, intraocular pressure 28 mmHg. Computed tomography with heterogeneous intraocular mass with hyperdense regions. With a diagnosis of probable retinoblastoma, enucleation was performed. Histopathology reported moderately differentiated retinoblastoma coexisting with PFV. Conclusions: The finding of these two diagnoses in the same eye is very rare due to the different pathophysiology.

Identification of Transcriptional Networks Involved in De Novo Organ Formation in Tomato Hypocotyl Explants.

Some of the hormone crosstalk and transcription factors (TFs) involved in wound-induced organ regeneration have been extensively studied in the model plant Arabidopsis thaliana. In previous work, we established Solanum lycopersicum "Micro-Tom" explants without the addition of exogenous hormones as a model to investigate wound-induced de novo organ formation. The current working model indicates that cell reprogramming and founder cell activation requires spatial and temporal regulation of auxin-to-cytokinin (CK) gradients in the apical and basal regions of the hypocotyl combined with extensive metabolic reprogramming of some cells in the apical region. In this work, we extended our transcriptomic analysis to identify some of the gene regulatory networks involved in wound-induced organ regeneration in tomato. Our results highlight a functional conservation of key TF modules whose function is conserved during de novo organ formation in plants, which will serve as a valuable resource for future studies.

Pulmonary Function and Respiratory Diseases in Different Genotypes of Alpha-1 Antitrypsin Deficiency.

OBJECTIVE: Respiratory disease is the major cause of morbidity and mortality in patients with alpha-1 antitrypsin deficiency, mainly in homozygous PI*ZZ individuals. However, this association is uncertain in subjects with other deficiency genotypes. The objective of this study was to assess, in the context of alpha-1 antitrypsin deficiency, the existence of further risk factors that have been associated with respiratory diseases. MATERIAL AND METHODS: Lung function was assessed by spirometry in a sample of 1334 patients with a known genotype for the SERPINA1 gene whose serum alpha-1 antitrypsin levels had been previously determined. Patients with a normal genotype (PI*MM) were compared to 389 patients carrying a deficiency allele. RESULTS: Statistically significant associations were detected between (i) PI*ZZ genotype and abnormal FEV1 values (χ2 = 26.45; P <.0002), FEV1/FVC (χ2 = 14.8; P < .02) or forced mid-expiratory flow 25%-75% (χ2 =22.66; P < .0009); (ii) chronic obstructive pulmonary disease and PI*ZZ odds ratio: 26.5; 95% CI: (2.6-265.9); P <.005 and or PI*SS genotype odds ratio: 9; 95% CI: (2-40.1); P < .004; (iii) prevalence of COPD in PI*MZ subjects and smoking habit (P < .01), low body weight (P < .01) or older age (P < .0001). CONCLUSION: The PI*ZZ and PI*SS genotypes seem to be associated with the prevalence of chronic obstructive pulmonary disease. Tobacco use, low body weight, and older age are risk factors that increase the probability of prevalence of chronic obstructive pulmonary disease by up to 70% in PI*MZ individuals.

Neumonía organizativa fibrinosa aguda asociada a tratamiento con inmunoterapia (pembrolizumab) / Acute Fibrinous and organizing Pneumonia Associated With Immunotherapy (Pembrolizumab)

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